FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Freedman, ML Haiman, CA Patterson, N McDonald, GJ Tandon, A Waliszewska, A Penney, K Steen, RG Ardlie, K John, EM Clakley-Girvan, I Whitternore, AS Cooney, KA Ingles, SA Altshuler, D Henderson, BE Reich, D AF Freedman, Matthew L. Haiman, Christopher A. Patterson, Nick McDonald, Gavin J. Tandon, Arti Waliszewska, Alicja Penney, Kathryn Steen, Robert G. Ardlie, Kristin John, Esther M. Clakley-Girvan, Ingrid Whitternore, Alice S. Cooney, Kathleen A. Ingles, Sue A. Altshuler, David Henderson, Brian E. Reich, David TI Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE association; human genetics ID COMPARATIVE GENOMIC HYBRIDIZATION; SUSCEPTIBILITY; GENES; POPULATIONS; MARKERS; MAP AB A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P < 4.2 x 10(-9)) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Biopolymers Facil, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. MIT, Cambridge, MA 02142 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Lab Mol Immunol, Boston, MA 02115 USA. SeraCare Life Sci Inc, Genom Collaborat, Cambridge, MA 02139 USA. No Calif Canc Ctr, Fremont, CA 94538 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Reich, D (reprint author), Harvard Univ, Sch Med, Dept Genet, New Res Bldg,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM reich@receptor.med.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [P50 CA069568, CA63464, CA67044, CA69568, CA79596, R01 CA063464, R01 CA067044, R01 CA079596, U01 CA063464, U01 CA067044]; NHGRI NIH HHS [HG02758, K01 HG002758] NR 26 TC 376 Z9 388 U1 1 U2 8 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 19 PY 2006 VL 103 IS 38 BP 14068 EP 14073 DI 10.1073/pnas.0605832103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 087MN UT WOS:000240746600031 PM 16945910 ER PT J AU Hiroi, Y Kim, HH Ying, H Furuya, F Huang, ZH Simoncini, T Noma, K Ulek, K Nguyen, NH Scanlan, TS Moskowitz, MA Cheng, SY Liao, JK AF Hiroi, Yukio Kim, Hyung-Hwan Ying, Hao Furuya, Fumihiko Huang, Zhihong Simoncini, Tommaso Noma, Kensuke Ulek, Kojiro Nguyen, Ngoc-Ha Scanlan, Thomas S. Moskowitz, Michael A. Cheng, Sheue-Yann Liao, James K. TI Rapid nongenomic actions of thyroid hormone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nitric oxide; phosphatidylinositol 3-kinase; protein kinase Akt; stroke ID NITRIC-OXIDE SYNTHASE; CEREBRAL BLOOD-FLOW; B C-AKT; VENTRICULAR MYOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; IN-VIVO; ACTIVATION; RECEPTOR; MICE; KINASE AB The binding of thyroid hormone to the thyroid hormone receptor (TR) mediates important physiological effects. However, the transcriptional effects of TR mediated by the thyroid response element (TRE) cannot explain many actions of thyroid hormone. We postulate that TR can initiate rapid, non-TRE-mediated effects in the cardiovascular system through cross-coupling to the phosphatidylinositol 3-kinase (P13-kinase)/protein kinase Akt pathway. In vascular endothelial cells, the predominant TR isoform is TR alpha(1). Treatment of endothelial cells with L-3,5,3'-triiodothyronine T-3 increased the association of TR alpha(1), with the p85 alpha subunit of P13-kinase, leading to the phosphorylation and activation of Akt and endothelial nitric oxide synthase (eNOS). The activation of Akt and eNOS by T-3 was abolished by the P13-kinase inhibitors, LY294002 and wortmannin, but not by the transcriptional inhibitor, actinomycin D. To determine the physiological relevance of this P13-kinase/Akt pathway, we administered T-3 to mice undergoing transient focal cerebral ischemia. Compared with vehicle, a single bolus infusion of T-3 rapidly increased Akt activity in the brain, decreased mean blood pressure, reduced cerebral infarct volume, and improved neurological deficit score. These neuroprotective effects of T-3 were greatly attenuated or absent in eNOS(-/-) and TR alpha(-/-)(1)beta(-/-) mice and were completely abolished in WT mice pretreated with LY294002 or a T-3 antagonist, NH-3. These findings indicate that the activation of P13-kinase/Akt pathways can mediate some of the rapid, non-TRE effects of TR and suggest that the activation of Akt and eNOS contributes to some of the acute vasodilatory and neuroprotective effects of thyroid hormone. C1 Brigham & Womens Hosp, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02139 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Lab Stroke & Neurovasc Regulat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo 1130033, Japan. Univ Pisa, Dept Reprod Med & Child Dev, I-56126 Pisa, Italy. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. RP Liao, JK (reprint author), Brigham & Womens Hosp, Cambridge, MA 02139 USA. EM jliao@rics.bwh.harvard.edu RI Moskowitz, Michael/D-9916-2011; OI Simoncini, Tommaso/0000-0002-2971-0079 FU NHLBI NIH HHS [HL070274, HL080187, R01 HL052233, R01 HL052233-11, R01 HL052233-12, R01 HL070274, R01 HL070274-03, R01 HL070274-04, R01 HL070274-05, R01 HL080187, R01 HL080187-03, R01 HL080187-04]; NIDDK NIH HHS [DK062729, R01 DK062729, R01 DK062729-04, R01 DK062729-05]; NINDS NIH HHS [F32 NS010828, NS010828, P01 NS010828, P50 NS010828] NR 36 TC 173 Z9 185 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 19 PY 2006 VL 103 IS 38 BP 14104 EP 14109 DI 10.1073/pnas.0601600103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 087MN UT WOS:000240746600037 PM 16966610 ER PT J AU Borsook, D Becerra, LR AF Borsook, David Becerra, Lino R. TI Breaking down the barriers: fMRI applications in pain, analgesia and analgesics SO MOLECULAR PAIN LA English DT Review ID IRRITABLE-BOWEL-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; HUMAN BRAIN; NEUROPATHIC PAIN; FUNCTIONAL MRI; NOXIOUS HEAT; RECTAL PAIN; CENTRAL SENSITIZATION AB This review summarizes functional magnetic resonance imaging ( fMRI) findings that have informed our current understanding of pain, analgesia and related phenomena, and discusses the potential role of fMRI in improved therapeutic approaches to pain. It is divided into 3 main sections: ( 1) fMRI studies of acute and chronic pain. Physiological studies of pain have found numerous regions of the brain to be involved in the interpretation of the ' pain experience'; studies in chronic pain conditions have identified a significant CNS component; and fMRI studies of surrogate models of chronic pain are also being used to further this understanding. ( 2) fMRI studies of endogenous pain processing including placebo, empathy, attention or cognitive modulation of pain. ( 3) The use of fMRI to evaluate the effects of analgesics on brain function in acute and chronic pain. fMRI has already provided novel insights into the neurobiology of pain. These insights should significantly advance therapeutic approaches to chronic pain. C1 McLean Hosp, Dept Psychiat, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Borsook, D (reprint author), McLean Hosp, Dept Psychiat, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02178 USA. EM dborsook@mclean.harvard.edu; lbecerra@mclean.harvard.edu FU NINDS NIH HHS [NS042721, R01 NS042721] NR 102 TC 46 Z9 47 U1 2 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD SEP 18 PY 2006 VL 2 AR 30 DI 10.1186/1744-8069-2-30 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 165BP UT WOS:000246279100001 PM 16982005 ER PT J AU Bernardi, RE Lattal, KM Berger, SP AF Bernardi, Rick E. Lattal, Kennon M. Berger, Stephen P. TI Postretrieval propranolol disrupts a cocaine conditioned place preference SO NEUROREPORT LA English DT Article DE cocaine; conditioned place preference; memory; reconsolidation ID RETROGRADE-AMNESIA; PROTEIN-SYNTHESIS; MEMORY CONSOLIDATION; RECONSOLIDATION; REACTIVATION; RETRIEVAL; AMYGDALA; REWARD; NEUROBIOLOGY; PERSPECTIVE AB The current study examined whether a postretrieval drug memory could be disrupted by the beta-adrenoceptor antagonist propranolol, administered following reactivation in a cocaine-mediated conditioned place preference paradigm. Following cocaine conditioning, rats were given a test of conditioned place preference, followed immediately by intraperitoneal administration of propranolol or saline. Rats that received propranolol following the preference test showed no preference for the cocaine-paired floor during a subsequent test, while vehicle-treated rats continued to express a preference for the cocaine-paired floor. These deficits in behavior were specific to retrieval of the cocaine-mediated memory, suggesting that postretrieval propranolol induced an impairment of drug-seeking behavior that is consistent with the disruption of a reconsolidation phase following retrieval. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Bernardi, RE (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, Mail Code L470,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM bernardi@ohsu.edu NR 25 TC 75 Z9 78 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 18 PY 2006 VL 17 IS 13 BP 1443 EP 1447 DI 10.1097/01.wnr.0000233098.20655.26 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 089JQ UT WOS:000240877100015 PM 16932155 ER PT J AU Oh, WY Bouma, BE Iftimia, N Yelin, R Tearney, GJ AF Oh, W. Y. Bouma, B. E. Iftimia, N. Yelin, R. Tearney, G. J. TI Spectrally-modulated full-field optical coherence microscopy for ultrahigh-resolution endoscopic imaging SO OPTICS EXPRESS LA English DT Article ID CONFOCAL MICROSCOPY; SPATIAL-RESOLUTION; IN-VIVO; TOMOGRAPHY AB Full-field optical coherence microscopy (FFOCM) utilizes coherence gating to obtain high-resolution optical sections in thick tissues. FFOCM is an attractive technology for endoscopic microscopy at the cellular level since it does not require a high NA objective lens or beam scanning and is therefore particularly amenable to miniaturization. In this manuscript, we present a novel scheme for conducting FFOCM that utilizes spectrally modulated, spatially incoherent illumination and a static Linnik interferometer. This approach is advantageous for endoscopic microscopy since it allows FFOCM to be conducted through a single multimode fiber optic imaging bundle and does not require moving parts in the endoscope probe. Images acquired from biological samples in free space demonstrate that this new method provides the same detailed microscopic structure as that of conventional FFOCM. High-resolution images were also obtained through a multimode fiber bundle, further supporting the potential of this method for endoscopic microscopy. (c) 2006 Optical Society of America C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Oh, WY (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 704, Boston, MA 02114 USA. EM woh1@partners.org RI Oh, Wang-Yuhl/C-2055-2011 FU NHLBI NIH HHS [R01 HL076398, R01 HL076398-02] NR 15 TC 39 Z9 39 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 SEP 18 PY 2006 VL 14 IS 19 BP 8675 EP 8684 DI 10.1364/OE.14.008675 PG 10 WC Optics SC Optics GA 085XW UT WOS:000240638700024 PM 19529248 ER PT J AU de Lemos, JA Wiviott, SD Murphy, SA Blazing, MA Lewis, EF Califf, RM Pfeffer, MA Braunwald, E AF de Lemos, James A. Wiviott, Stephen D. Murphy, Sabina A. Blazing, Michael A. Lewis, Eldrin F. Califf, Robert M. Pfeffer, Marc A. Braunwald, Eugene TI Evaluation of the National Cholesterol Education Program Adult Treatment Panel III algorithm for selecting candidates for statin therapy: Insights from the A to Z trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; TO-Z TRIAL; EFFICACY; RATIONALE; TIROFIBAN; HEPARIN; SAFETY AB The National Cholesterol Education Program Adult Treatment Panel III recommends an algorithm to integrate iterative risk-stratification information with low-density lipoprotein (LDL) cholesterol levels to identify candidates for statin therapy. We used the Aggrastat to Zocor (A to Z) trial, in which all patients presented with an acute coronary syndrome (ACS) event in the absence of previous statin therapy, to evaluate the performance of this algorithm. Of 1,750 patients with ACS included in this analysis, 1,126 (64%) bad an indication for statin therapy before enrollment and 624 (36%) did not have a statin indication before enrollment. We estimate that initiating statin therapy at moderate dosages (decreasing LDL by 1 mmol/L) according to the National Cholesterol Education Program Adult Treatment Panel III guidelines would have prevented approximately 15% of the ACS events leading to enrollment in the A to Z trial, whereas more intensive statin therapy (decreasing LDL by 1.5 mmol/Li would have prevented > 21% of events. Aspirin use before enrollment was reported in only 38% of subjects with a statin indication. In conclusion, these observations represent missed opportunities for primary and secondary prevention and highlight the need for assessment of patient risk and better adherence to existing prevention guidelines. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75235 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Duke Univ, Clin Res Inst, Durham, NC USA. RP de Lemos, JA (reprint author), Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75235 USA. EM james.delemos@utsouthwestern.edu NR 8 TC 6 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2006 VL 98 IS 6 BP 739 EP 742 DI 10.1016/j.amjcard.2006.03.060 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 087AR UT WOS:000240715100007 PM 16950174 ER PT J AU Gibson, CM Ly, HQ Murphy, SA Ciaglo, LN Southard, MC Stein, EB Buros, JL Sabatine, MS Cannon, CP AF Gibson, C. Michael Ly, Hung Q. Murphy, Sabina A. Ciaglo, Lauren N. Southard, Matthew C. Stein, Erica B. Buros, Jacqueline L. Sabatine, Marc S. Cannon, Christopher P. CA TIMI Study Grp TI Usefulness of clopidogrel in abolishing the increased risk of reinfarction associated with higher platelet counts in patients with ST-elevation myocardial infarction (Results from CLARITY-TIMI 28) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FIBRINOLYTIC THERAPY; SEGMENT ELEVATION; THROMBOLYSIS; ASPIRIN; TRIAL AB Previous studies have demonstrated an association between increased baseline platelet counts and poorer clinical and angiographic outcomes in patients with ST-elevation myocardial infarction (STEMI). We hypothesized that antiplatelet therapy would mitigate the effect of high baseline platelet counts on clinical outcomes.. Data were obtained. from 3,491 patients with STEMI in the CLARITY-TIMI 28 trial. Patients were categorized into 3 groups based on their baseline platelet counts: < 200 X 10(3)/mu l (group 1), 200 to 300 X 10(3)/mu l (group 2), and > 300 X 10(3)/mu l (group 3). Among placebo-treated patients, reinfarction rates-increased in a stepwise fashion as platelet counts increased (3.6%, 5.4%, and 9.0%, respectively, p for trend = 0.0025). When confounders of high platelet counts and correlates of reinfarction were adjusted for in a multivariate model, high platelet counts remained independently associated with increased rates of reinfarction at 30 days in placebo-treated patients; using group I as a reference group, multivariate odds ratios were 1.45 (95% confidence interval 0.91 to 2.31, p = 0.119) for patients in group 2 and 1.78 (95% confidence interval 1.03 to 3.08, p = 0.038) for patients in group 3. In contrast, among clopidogrel-treated patients, there was no increase in the risk of reinfarction as the platelet count increased (3.2%, 4.1%, and 3.3%, respectively; p for trend = 0.9073, p for interaction = 0.064). In conclusion, among patients with STEMI who are treated with aspirin and a fibrinolytic agent, high platelet counts on presentation are independently associated with increased rates of reinfarction. Clopidogrel therapy abolishes this increase in the risk of reinfarction as platelet counts increase. These data are consistent with a putative role of platelets in reinfarction. (c) 2006 Elsevier Inc. C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc, Boston, MA 02215 USA. RP Gibson, CM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mgibson@perfuse.org OI Buros, Jacqueline/0000-0001-9588-4889 NR 7 TC 12 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2006 VL 98 IS 6 BP 761 EP 763 DI 10.1016/j.amjcard.2006.03.062 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 087AR UT WOS:000240715100013 PM 16950180 ER PT J AU Siebert, U Januzzi, JL Beinfeld, MT Cameron, R Gazelle, GS AF Siebert, Uwe Januzzi, James L., Jr. Beinfeld, Molly T. Cameron, Renee Gazelle, G. Scott TI Cost-effectiveness of using N-terminal, pro-brain natriuretic peptide to guide the diagnostic assessment and management of dyspneic patients in the emergency department SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB The cost-effectiveness of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in dyspneic patients in emergency departments (EDs) is unknown. The objective of this study was to assess the cost-effectiveness of NT-pro-BNP testing for the evaluation and initials management of patients with dyspnea in the ED setting. A decision model was developed to evaluate the cost-effectiveness of diagnostic assessment and patient management guided by NT-pro-BNP, compared with standard clinical assessment. The model includes the diagnostic accuracy of the 2 strategies for congestive heart failure and resulting events at 60-day follow-up. Clinical data were obtained from a prospective blinded study of 599 patients presenting to the ED with dyspnea. Costs were based on the Massachusetts General Hospital cost accounting database. The model predicted serious adverse events during follow-up (i.e., urgent care visits, repeat ED presentations, rehospitalizations) and direct medical costs for echocardiograms and hospitalizations. NT-pro-BNP-guided assessment was associated with a 1.6% relative reduction of serious adverse event risk and a 9.4% reduction in costs, translating into savings of $474 per patient, compared with standard clinical assessment. In a sensitivity analysis considering mortality, NT-pro-BNP testing was associated with a 1.0% relative reduction in post-discharge mortality. The optimal use of NT-pro-BNP guidance could reduce the use of echocardiography by up to 58%, prevent 13% of initial hospitalizations, and reduce hospital days by 12%. In conclusion, on the basis of this model, the use of NT-pro-BNP in the diagnostic assessment and subsequent management of patients with dyspnea in the ED setting could lead to improved patient care while providing substantial cost savings to the health care system. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Siebert, U (reprint author), Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM usiebert@hsph.harvard.edu NR 14 TC 45 Z9 47 U1 0 U2 2 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2006 VL 98 IS 6 BP 800 EP 805 DI 10.1016/j.amjcard.2006.06.005 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 087AR UT WOS:000240715100022 PM 16950189 ER PT J AU Esteves, CA Munoz, JS Braga, S Andrade, J Meneghelo, Z Gornes, N Maldonado, M Esteves, V Sepetiba, R Sousa, JE Palacios, IF AF Esteves, Cesar A. Munoz, Juan S. Braga, Sergio Andrade, Januario Meneghelo, Zilda Gornes, Nisia Maldonado, Mercedes Esteves, Vinicius Sepetiba, Rodrigo Sousa, J. Eduardo Palacios, Igor F. TI Immediate and long-term follow-up of percutaneous balloon mitral valvuloplasty in pregnant patients with rheumatic mitral stenosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID INOUE BALLOON; VALVOTOMY; COMMISSUROTOMY; WOMEN; DILATATION; VARIABLES; CATHETER; CHOICE; VALVE AB Percutaneous mitral balloon valvuloplasty (PMV) can be performed during pregnancy Without significant maternal risk or fetal morbidity or mortality. However, little is known about long-term follow-up results after PMV in populations of pregnant women. Thus, the present study was undertaken to determine the immediate and long-term outcomes after PMV in a large cohort of pregnant patients with severe mitral stenosis. The patient population consisted of 71 consecutive pregnant women with severe rheumatic mitral stenosis admitted to the hospital with severe congestive heart failure (New York Heart Association class III and IV) for PMV. All patients underwent clinical and obstetric evaluations, electrocardiography, and 2-dimensional and Doppler echocardiography. PMV was successful in all patients, resulting in a significant increase in mitral valve area from 0.9 +/- 0.2 to 2.0 +/- 0.3 cm(2) (p < 0.001). At the end of pregnancy, 98% of the patients were in New York Heart Association functional class I or II. At a mean follow-up of 44 +/- 31 months, the total event-free survival rate was 54%. The mean gestational age at delivery time was 38 +/- 1 weeks. Preterm deliveries occurred in 9 patients (13%), including 2 twin pregnancies. The remaining 66 of 75 newborns (88%) had normal weight (mean 2.8 +/- 0.6 kg) at delivery. At long-term follow-up of 44 +/- 31 months after birth, the 66 children exhibited normal growth and development and did not show any clinical abnormalities. In conclusion, PMV is safe and effective, has a low morbidity and mortality rate for the mother and the fetus, and has favorable long-term results in pregnant women with rheumatic mitral stenosis in New York Heart Association functional class III or IV. (c) 2006 Elsevier Inc. All rights reserved. C1 Inst Dante Pazzanese Cardiol, Sao Paulo, Brazil. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Palacios, IF (reprint author), Inst Dante Pazzanese Cardiol, Sao Paulo, Brazil. EM palacios.igor@mgh.harvard.edu NR 26 TC 21 Z9 23 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2006 VL 98 IS 6 BP 812 EP 816 DI 10.1016/j.amjcard.2006.03.068 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 087AR UT WOS:000240715100025 PM 16950192 ER PT J AU Angel, LF Levine, DJ Restrepo, MI Johnson, S Sako, E Carpenter, A Calhoon, J Cornell, JE Adams, SG Chisholm, GB Nespral, J Roberson, A Levine, SM AF Angel, Luis F. Levine, Deborah J. Restrepo, Marcos I. Johnson, Scott Sako, Edward Carpenter, Andrea Calhoon, John Cornell, John E. Adams, Sandra G. Chisholm, Gary B. Nespral, Joe Roberson, Ann Levine, Stephanie M. TI Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lung recipients; lung transplantation; organ donation; organ donor; survival ID RESPIRATORY-DISTRESS-SYNDROME; CRITERIA; LIBERALIZATION; RECRUITMENT; EXPERIENCE; ORGANS AB Rationale: One of the limitations associated with lung transplantation is the lack of available organs. Objective: To determine whether a lung donor-management protocol could increase the number of lungs for transplantation without affecting the survival rates of the recipients. Methods: We implemented the San Antonio Lung Transplant protocol for managing potential lung donors according to modifications of standard criteria for donor selection and strategies for donor management. We then compared information gathered during a 4-yr period, during which the protocol was used with information gathered during a 4-yr period before protocol implementation. Primary outcome measures were the procurement rate of lungs and the 30-d and 1-yr survival rates of recipients. Main Results: We reviewed data from 711 potential lung donors. The mean rate of lung procurement was significantly higher (p < 0.0001) during the protocol period (25.5%) than during the preprotocol period (111.5%), with an estimated risk ratio of 2.2 in favor of the protocol period. More patients received transplants during the protocol period (n = 121) than during the pre-protocol period (n = 53; p < 0.0001). Of 98 actual lung donors during the protocol period, 53 (54%) had initially been considered poor donors; these donors provided 64 (53%) of the 121 lung transplants. The type of donor was not associated with significant differences in recipients' 30-d and 1-yr survival rates or any clinical measures of adequate graft function. Conclusions: The protocol was associated with a significant increase in the number of lung donors and transplant procedures without compromising pulmonary function, length of stay, or survival of the recipients. C1 Univ Texas, Hlth Sci Ctr, Div Cardiothorac Surg, Div Pulm & Crit Care Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Ctr Biostat & Epidemiol, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, VERDICT, Ctr Excellence, San Antonio, TX 78284 USA. Texas Organ Sharing Alliance, San Antonio, TX USA. RP Angel, LF (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM angel@uthscsa.edu NR 33 TC 83 Z9 85 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 15 PY 2006 VL 174 IS 6 BP 710 EP 716 DI 10.1164/rccm.200603-432OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 086HJ UT WOS:000240664100015 PM 16799075 ER PT J AU Kasper, JS Arai, T DeCaprio, JA AF Kasper, Jocelyn S. Arai, Takehiro DeCaprio, James A. TI A novel p53-binding domain in CUL7 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cullin RING ligase; SKP-cullin-F box; CUL7; p53; PARC; ubiquitin-protein ligases; sequence homology; tumor suppressors ID LARGE-T-ANTIGEN; SCF UBIQUITIN LIGASE; RING-FINGER DOMAIN; POSTTRANSLATIONAL MODIFICATION; CELLULAR-TRANSFORMATION; TUMOR-ANTIGEN; P53; MDM2; PROTEINS; COMPLEX AB CUL7 is a member of the cullin RING ligase family and forms an SCF-like complex with SKP1 and FBXW8. CUL7 is required for normal mouse embryonic development and cellular proliferation, and is highly homologous to PARC, a p53-associated, parkin-like cytoplasmic protein. We determined that CUL7, in a manner similar to PARC, can bind directly to p53. but does not affect p53 expression. We identified a discrete, co-linear domain in CUL7 that is conserved in PARC and HERC2, and is necessary and sufficient for p53-binding. The presence of p53 stabilized expression of this domain and we demonstrate that this p53-binding domain of CUL7 contributes to the cytoplasmic localization of CULT The results support the model that p53 plays a role in regulation of CUL7 activity, (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [R01 CA 93804] NR 37 TC 14 Z9 16 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 15 PY 2006 VL 348 IS 1 BP 132 EP 138 DI 10.1016/j.bbrc.2006.07.013 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 074ES UT WOS:000239796100018 PM 16875676 ER PT J AU Ahveninen, J Jaaskelainen, IP Osipova, D Huttunen, MO Ilmoniemi, RJ Kaprio, J Lonnqvist, J Manninen, M Pakarinen, S Therman, S Naatanen, R Cannon, TD AF Ahveninen, Jyrki Jaaskelainen, Iiro P. Osipova, Daria Huttunen, Matti O. Ilmoniemi, Risto J. Kaprio, Jaakko Lonnqvist, Jouko Manninen, Marko Pakarinen, Satu Therman, Sebastian Naatanen, Risto Cannon, Tyrone D. TI Inherited auditory-cortical dysfunction in twin pairs discordant for schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE auditory cortex; electroencephalography (EEG); magnetoencephalography (MEG); schizophrenia; twins ID EVENT-RELATED POTENTIALS; EVOKED RESPONSE SUPPRESSION; MISMATCH NEGATIVITY; MAGNETIC-FIELDS; HUMAN-BRAIN; BIOLOGICAL RELATIVES; ABNORMALITIES; REDUCTION; EXPERIENCES; MECHANISMS AB Background-Information on the inheritance of neurophysiological abnormalities might help elucidate the molecular genetic basis of schizophrenia. We used magnetoencephalography (MEG) and electroencephalography (EEG) to investigate the inheritance of auditory-cortical deficiencies in twin pairs discordant for schizophrenia. Methods: Auditory EEG/MEG responses to frequent standard and occasional deviant tones were measured in mono- and dizygotic (MZ and DZ) twin pairs discordant for schizophrenia and demographically matched healthy twin pairs, recruited from a total population cohort. The MEG/EEG results were regressed against the genetic resemblance to patients with schizophrenia across the patients' unaffected MZ/DZ co-twins and control subjects (with genetic correlations of 1, .5, and 0 to schizophrenia patients, respectively). Results. The EEG responses P50, N100, and mismatch negativity (MMN), as well as the MEG response P50m, were reduced in the schizophrenic patients. P50 and N100 were significantly decreased also in their unaffected co-twins, as compared with the control subjects. Importantly, the P50 and N100 decrease correlated with the unaffected subjects' genetic resemblance to schizophrenia patients. Conclusions: Our results suggest inherited abnormalities in cortical auditory processing in schizophrenia, reflected by the decreased P50/P50m and N100 amplitudes, whereas the MMN abnormalities might reflect predominantly state-dependent neurodegeneration. C1 Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Univ Helsinki, Dept Publ Hlth, Cognit Brain Res Unit, Helsinki, Finland. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Ctr Engn, Helsinki, Finland. Helsinki Univ Technol, Lab Computat Engn, FIN-02150 Espoo, Finland. Brain Res Ctr, Helsinki, Finland. Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. RP Ahveninen, J (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Sch Med, CNY 149 13th St, Charlestown, MA 02129 USA. EM jyrki@nmr.mgh.harvard.edu RI Kaprio, Jaakko/A-1820-2008; Jaaskelainen, Iiro/C-7392-2012; Ilmoniemi, Risto/E-9704-2012; OI Kaprio, Jaakko/0000-0002-3716-2455; Jaaskelainen, Iiro/0000-0001-6001-6950; Ilmoniemi, Risto/0000-0002-3340-2618; Manninen, Marko/0000-0002-1096-1185; Therman, Sebastian/0000-0001-9407-4905 FU NICHD NIH HHS [R01 HD040712]; NIMH NIH HHS [MH 52857] NR 66 TC 50 Z9 52 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2006 VL 60 IS 6 BP 612 EP 620 DI 10.1016/j.biopsych.2006.04.015 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 088WB UT WOS:000240840700014 PM 16876141 ER PT J AU Shen, RR Ferguson, DO Renard, M Hoyer, KK Kim, U Hao, XP Alt, FW Roeder, RG Morse, HC Teitell, MA AF Shen, Rhine R. Ferguson, David O. Renard, Mathilde Hoyer, Katrina K. Kim, Unkyu Hao, Xingpei Alt, Frederick W. Roeder, Robert G. Morse, Herbert C., III Teitell, Michael A. TI Dysregulated TCL1 requires the germinal center and genome instability for mature B-cell transformation SO BLOOD LA English DT Article ID INDUCED-CYTIDINE-DEAMINASE; FAS-MEDIATED APOPTOSIS; CLASS SWITCH RECOMBINATION; C-MYC; CHROMOSOMAL TRANSLOCATIONS; ANTIGEN RECEPTOR; BURKITT-LYMPHOMA; PROLYMPHOCYTIC LEUKEMIA; DEREGULATED EXPRESSION; FOLLICULAR LYMPHOMA AB Most lymphomas arise by transformation of germinal center (GC) B cells. TCL1, a proto-oncogene first recognized for its role in T-cell transformation, also induces GC B-cell malignancies when dysregulated in pE mu-B29-TCL1 transgenic (TCL1-tg) mice. Clonal B-cell lymphomas develop from polyclonal populations with latencies of 4 months or more, suggesting that secondary genetic events are required for full transformation. The goals of this study were to determine the GC-related effects of TCL1 dysregulation that contribute to tumor initiation and to identify companion genetic alterations in tumors that function in disease progression. We report that compared with wildtype (WT) cells, B cells from TCL1-tg mice activated in a manner resembling a T-dependent GC reaction show enhanced resistance to FAS-mediated apoptosis with CD40 stimulation, independent of a B-cell antigen receptor (BCR) rescue signal. Mitogenic stimulation of TCL1-tg B cells also resulted in increased expression of Aicda. These GC-related enhancements in survival and Aicda expression could underlie B-cell transformation. Supporting this notion, no B-cell lymphomas developed for 20 months when TCL1-tg mice were crossed onto an Oct coactivator from B cell (OCA-B)-deficient background to yield mice incapable of forming GCs. Spectral karyotype analyses showed that GC lymphomas from TCL1-tg mice exhibit recurrent chromosome translocations and trisomy 15, with corresponding MYC overexpression. We conclude that pE mu-B29-TCL1 transgenic B cells primed for transformation must experience the GC environment and, for at least some, develop genome instability to become fully malignant. C1 Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NIAID, Immunopathol Lab, NIH, Rockville, MD USA. RP Teitell, MA (reprint author), Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mteitell@ucla.edu OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA 107300, CA 90571, CA 109901, CA 113872, CA 92625]; NIAID NIH HHS [T32 AI 07126] NR 66 TC 11 Z9 13 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 SEP 15 PY 2006 VL 108 IS 6 BP 1991 EP 1998 DI 10.1182/blood-2006-02-001354 PG 8 WC Hematology SC Hematology GA 082NY UT WOS:000240394800039 PM 16728701 ER PT J AU Chakraverty, R Eom, HS Sachs, J Buchli, J Cotter, P Hsu, R Zhao, GL Sykes, M AF Chakraverty, Ronjon Eom, Hyeon-Seok Sachs, Jessica Buchli, Jennifer Cotter, Pete Hsu, Richard Zhao, Guiling Sykes, Megan TI Host MHC class II+ antigen-presentirig cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; T-CELLS; LYMPHOCYTE INFUSION; ALLOANTIGEN EXPRESSION; NEGATIVE SELECTION; CRUCIAL ROLE; DISEASE; TOLERANCE; CHIMERAS; MICE AB Following bone marrow transplantation, delayed donor leukocyte infusions (DLIs) can induce graft-versus-leukemia (GVL) effects without graft-versus-host disease (GVHD). These antitumor responses are maximized by the presence of host hematopoietic antigen-presenting cells (APCs) at the time of DLI. Using a tumor-protection model, we demonstrate here that GVIL activity following administration of DLIs to established mixed chimeras is dependent primarily on reactivity to allogeneic MHC antigens rather than minor histocompatibility or tumor-associated antigens. CD8(+) T-cell-dependent GVL responses against an MHC class II-negative tumor following delayed DLI require CD4(+) T-cell help and are reduced significantly when host APCs lack MHC class II expression. CD4(+) T cells primed by host APCs were required for maximal expansion of graft-versus-host reactive CD8(+) T cells but not their synthesis of IFN-gamma. In contrast, the GVL requirement for CD4(+) T-cell help was bypassed almost completely when DLI was administered to freshly irradiated recipients, indicating that the host environment is a major factor influencing the cellular mechanisms of GVL. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Transplantat Biol R, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Transplantat Biol R, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [R01 CA 79989] NR 42 TC 55 Z9 55 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2006 VL 108 IS 6 BP 2106 EP 2113 DI 10.1182/blood-2006-03-007427 PG 8 WC Hematology SC Hematology GA 082NY UT WOS:000240394800054 PM 16757687 ER PT J AU Bastian, PJ Gonzalgo, ML Aronson, WJ Terris, MK Kane, CJ Amling, CL Presti, JC Mangold, LA Humphreys, E Epstein, JI Partin, AW Freedland, SJ AF Bastian, Patrick J. Gonzalgo, Mark L. Aronson, William J. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Presti, Joseph C., Jr. Mangold, Leslie A. Humphreys, Elizabeth Epstein, Jonathan I. Partin, Alan W. Freedland, Stephen J. TI Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10 SO CANCER LA English DT Article DE Gleason score 8 to 10; high risk; prostate cancer; recurrence; radical prostatectomy ID RETROPUBIC PROSTATECTOMY; RADIATION-THERAPY; SEARCH DATABASE; RISK; RECURRENCE; DISEASE; ANTIGEN; PROGRESSION; MORTALITY; MEN AB BACKGROUND. Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS. The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS. Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS. The majority of men with a biopsy Gleason sum of >= 8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum < 8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation. C1 Duke Univ, Med Ctr, Div Urol Surg, Duke Prostate Ctr,Sch Med, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Surg, Duke Prostate Ctr, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Pathol, Duke Prostate Ctr, Durham, NC 27710 USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, Durham, NC USA. Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA. Vet Adm Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Vet Adm Med Ctr, Dept Surg, Augusta, GA 30904 USA. Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Univ Alabama, Dept Urol, Birmingham, AL USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Naval Hosp, Dept Urol, San Diego, CA USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, Palo Alto, CA 94304 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Div Urol Surg, Duke Prostate Ctr,Sch Med, Box 3850, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50CA58236, P50CA92131-01A1, R01CA100938] NR 32 TC 69 Z9 71 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2006 VL 107 IS 6 BP 1265 EP 1272 DI 10.1002/cncr.22116 PG 8 WC Oncology SC Oncology GA 084MR UT WOS:000240537700009 PM 16900523 ER PT J AU Xing, DY Orsulic, S AF Xing, Deyin Orsulic, Sandra TI A mouse model for the molecular characterization of Brca1-associated ovarian carcinoma SO CANCER RESEARCH LA English DT Article ID MULTIPLE GENETIC CHANGES; BRCA1; CANCER; CELLS; TP53; MUTATION; BREAST; MYC; TUMORIGENESIS; RESISTANCE AB Little is known about the mechanisms that underlie Brca1-associated ovarian tumorigenesis, mainly due to the lack of an appropriate experimental model. We developed genetically defined primary mouse ovarian surface epithelial (OSE) cell lines in which the loss of functional Brca1 and p53 recapitulates the events that are thought to occur in early ovarian cancer development in patients with Brca1 mutations. This system allows for the introduction of additional oncogenes that are thought to cooperate with the loss of Brca1 and p53 to induce tumorigenesis. We showed that Myc is sufficient to induce transformation of ovarian cells that are deficient for both Brca1 and p53 but not sufficient for the transformation of cells that are deficient for either Brca1 or p53. The transformed Brca1-deficient OSE cells display an increased number of centrosomes, acquire complex chromosome aberrations, and lack Rad51 nuclear foci in the presence of DNA-damaging agents, such as mitomycin C and cisplatin. Immunocompetent mice injected with transformed OSE cells develop tumors that resemble human metastatic serous ovarian carcinoma, the most common type of ovarian cancer in women. Consistent with the reported platinum chemosensitivity in patients with Brca1-associated ovarian cancer, the Brca1-deficient OSE cells have increased sensitivity to the DNA-damaging agent cisplatin, whereas sensitivity to the microtubule poison paclitaxel is similar between Brca1 wildtype and Brca1-deficient cells. The Brca1 wild-type and Brca1-deficient mouse ovarian tumors and cell lines provide a new experimental system for the evaluation of therapies that target the Brca1 pathway. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Orsulic, S (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 13th St,Bldg 149,CNY7, Charlestown, MA 02129 USA. EM sorsulic@partners.org FU NCI NIH HHS [R01 CA103924, P50 CA105009, P50CA105009, R01CA103924, U01 CA105492, UO1CA105492] NR 20 TC 59 Z9 63 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 SEP 15 PY 2006 VL 66 IS 18 BP 8949 EP 8953 DI 10.1158/0008-5472.CAN-06-1495 PG 5 WC Oncology SC Oncology GA 086CI UT WOS:000240650300005 PM 16982732 ER PT J AU Pejovic, T Yates, JE Liu, HY Hays, LE Akkari, Y Torimaru, Y Keeble, W Rathbun, RK Rodgers, WH Bale, AE Ameziane, N Zwaan, CM Errami, A Thuillier, P Cappuccini, F Olson, SB Cain, JM Bagby, GC AF Pejovic, Tanja Yates, Jane E. Liu, Hong Y. Hays, Laura E. Akkari, Yassmine Torimaru, Yumi Keeble, Winifred Rathbun, R. Keaney Rodgers, William H. Bale, Allen E. Ameziane, Najim Zwaan, C. Michael Errami, Abdellatif Thuillier, Philippe Cappuccini, Fabio Olson, Susan B. Cain, Joanna M. Bagby, Grover C., Jr. TI Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer SO CANCER RESEARCH LA English DT Article ID FANCONI-ANEMIA PROTEIN; FUNCTIONAL-ACTIVITY; BREAST CARCINOMAS; TUMORS; GENE; EXPRESSION; ONCOGENE; PATHWAY; FANCD2; P53 AB Fanconi anemia is an inherited cancer predisposition disease characterized by cytogenetic and cellular hypersensitivity to cross-linking agents. Seeking evidence of Fanconi anemia protein dysfunction in women at risk of ovarian cancer, we screened ovarian surface epithelial cells from 25 primary cultures established from 22 patients using cross-linker hypersensitivity assays. Samples were obtained from (a) women at high risk for ovarian cancer with histologically normal ovaries, (b) ovarian cancer patients, and (c) a control group with no family history of breast or ovarian cancer. In chromosomal breakage assays, all control cells were mitomycin C (MMC) resistant, but eight samples (five of the six high-risk and three of the eight ovarian cancer) were hypersensitive. Lymphocytes from all eight patients were MMC resistant. Only one of the eight patients had a BRCA1 germ-line mutation and none had BRCA2 mutations, but FANCD2 was reduced in five of the eight. Ectopic expression of normal FANCD2 cDNA increased FANCD2 protein and induced MMC resistance in both hypersensitive lines tested. No FANCD2 coding region or promoter mutations were found, and there was no genomic loss or promoter methylation in any Fanconi anemia genes. Therefore, in high-risk women with no BRCA1 or BRCA2 mutations, tissue-restricted hypersensitivity to cross-linking agents is a frequent finding, and chromosomal breakage responses to MMC may be a sensitive screening strategy because cytogenetic instability identified in this way antedates the onset of carcinoma. Inherited mutations that result in tissue-specific FANCD2 gene suppression may represent a cause of familial ovarian cancer. C1 Oregon Hlth Sci Univ, Dept Obstet & Gynecol, Inst Canc, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Ctr Womens Hlth, Inst Canc, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med & Mol & Med Genet, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, NW Vet Affairs Canc Res Ctr, Portland, OR USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT USA. MRC, Amsterdam, Netherlands. Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Pediat Oncol, Rotterdam, Netherlands. RP Pejovic, T (reprint author), Oregon Hlth Sci Univ, Dept Obstet & Gynecol, Inst Canc, L-466,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM pejovict@ohsu.edu FU NHLBI NIH HHS [HL48546]; NICHD NIH HHS [5K12HD043488] NR 40 TC 27 Z9 30 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 SEP 15 PY 2006 VL 66 IS 18 BP 9017 EP 9025 DI 10.1158/0008-5472.CAN-06-0222 PG 9 WC Oncology SC Oncology GA 086CI UT WOS:000240650300016 PM 16982743 ER PT J AU Aghi, M Cohen, KS Klein, RJ Scadden, DT Chioccra, EA AF Aghi, Manish Cohen, Kenneth S. Klein, Rachael J. Scadden, David T. Chioccra, E. Antonio TI Tumor stromal-derived factor-1 recruits vascular progenitors to mitotic neovasculature, where microenvironment influences their differentiated phenotypes SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HEMATOPOIETIC STEM-CELLS; HUMAN GLIOBLASTOMA; POSTNATAL NEOVASCULARIZATION; ANGIOGENESIS; CONTRIBUTE; SDF-1; VEGF; EXPRESSION; RECEPTOR AB Mechanisms underlying tumor vasculogenesis, the homing and engraftment of bone marrow-derived vascular progenitors, remain undefined. We hypothesized that tumor cell-secreted factors regulate vasculogenesis. We studied vasculogenic and nonvasculogenic intracranial murine gliomas. A PCR screen identified stromal-derived factor-1 (SDF-1/CXCL12) and vascular endothelial growth factor (VEGF) expression by vasculogenic glioma cells and spontaneously arising vasculogenic tumors in NF1(+/-):Trp53(+/-) mice, but not by nonvasculogenic glioma cells. Enforced SDF-1, not VEGF, expression in nonvasculogenic cells caused vasculogenesis. Combined SDF-1 and VEGF expression augmented vasculogenesis over SDF-1 expression alone. Blocking SDF-1 receptor CXCR4 reduced short-term homing and long-term engraftment of vascular progenitors. Implanting tumor cells secreting SDF-1 was therefore necessary and sufficient to incorporate marrow-derived precursors into tumor endothelium. SDF-1 seemed to exert these effects by acting locally intratumorally and did not cause an efflux of marrow-derived progenitors into circulation. Tumor microenvironment determined additional fates of marrow-derived cells. Hypoxia, observed with ectopic s.c. murine tumors at levels approximating that of intracranial human glioblastoma, interacted with tumor-secreted SDF-1 to expand engrafted vascular progenitor differentiated phenotypes to include pericytes as well as endothelium. In contrast, less hypoxic orthotopic intracranial murine gliomas contained only marrow-derived endothelium without marrow-derived pericytes. Furthermore, we found that vasculogenesis is significant for tumors because it generates endothelium with a higher mitotic index than endothelium derived from local sources. Although CXCR4 blockade selectively targeted endothelium generated by vasculogenesis, completely inhibiting vessel formation may require combination therapy targeting locally derived and marrow-derived endothelium. C1 Ohio State Univ, Med Ctr, Dept Neurol Surg,Dardinger Lab Neurooncol & Neuro, James Canc Hosp,Comprehens Canc Ctr, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, Solove Res Inst, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Program Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chioccra, EA (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg,Dardinger Lab Neurooncol & Neuro, James Canc Hosp,Comprehens Canc Ctr, N-1017 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM Dscadden@Partners.org; EA.Chiocca@osumc.edu FU NCI NIH HHS [R01 CA85139, P01 CA69246]; NHLBI NIH HHS [K08 HL071938]; NINDS NIH HHS [NS41571] NR 50 TC 118 Z9 131 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2006 VL 66 IS 18 BP 9054 EP 9064 DI 10.1158/0008-5472.CAN-05-3759 PG 11 WC Oncology SC Oncology GA 086CI UT WOS:000240650300020 PM 16982747 ER PT J AU Bauer, S Yu, LK Demetri, GD Fletcher, JA AF Bauer, Sebastian Yu, Lynn K. Demetri, George D. Fletcher, Jonathan A. TI Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; CHEMOTHERAPY-INDUCED APOPTOSIS; SCHEDULE-DEPENDENT MANNER; C-KIT; KINASE INHIBITOR; BCR-ABL; PHASE-I; COMBINING CYTOTOXICS; BIOLOGY MATTERS; LEUKEMIA-CELLS AB Inhibition of KIT oncoproteins by imatinib induces clinical responses in most gastrointestinal stromal tumor (GIST) patients. However, many patients develop imatinib resistance due to secondary KIT mutations. Heat shock protein 90 (HSP90) protects KIT oncoproteins from proteasome-mediated degradation, and we therefore did preclinical validations of the HSP90 inhibitor, 17-allylamino-18-demethoxy-geldanamycin (17-AAG), in an imatinib-sensitive GIST cell line (GIST882) and in novel imatinib-resistant GIST lines that are either dependent on (GIST430 and GIST48) or independent of (GIST62) KIT oncoproteins. 17AAG (> 100 nmol/L) inhibited imatinib-sensitive and imatinib-resistant KIT oncoproteins, with substantially reduced phospho-KIT and total KIT expression after 30 minutes and 6 hours, respectively. KIT signaling intermediates, including AKT and mitogen-activated protein kinase, were inactivated by 17-AAG in the KIT-positive GIST lines, but not in the KIT-negative GIST62. Likewise, cell proliferation and survival were inhibited in the KIT-positive GISTs but not in GIST62. These findings suggest that 17-AAG biological effects in KIT-positive GISTs result mainly from KIT oncoprotein inhibition. The dramatic inactivation of imatinib-resistant KIT oncoproteins suggests that HSP90 inhibition provides a therapeutic solution to the challenge of heterogeneous imatinib resistance mutations in GIST patients. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. RP Bauer, S (reprint author), Univ Essen Gesamthsch, W German Canc Ctr, Dept Internal Med Canc Res, Hufelandstr 55, D-45122 Essen, Germany. EM sebastianbauer@uni-essen.de RI Bauer, Sebastian/D-8120-2012 OI Bauer, Sebastian/0000-0001-5949-8120 NR 43 TC 161 Z9 166 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2006 VL 66 IS 18 BP 9153 EP 9161 DI 10.1158/0008-5472.CAN-06-0165 PG 9 WC Oncology SC Oncology GA 086CI UT WOS:000240650300031 PM 16982758 ER PT J AU Cai, DP Latham, VM Zhang, XX Shapiro, GI AF Cai, Dongpo Latham, Vaughan M., Jr. Zhang, Xinxin Shapiro, Geoffrey I. TI Combined depletion of cell cycle and transcriptional cyclin-dependent kinase activities induces apoptosis in cancer cells SO CANCER RESEARCH LA English DT Article ID FLAVOPIRIDOL-INDUCED APOPTOSIS; TERMINAL DOMAIN CTD; RNA-POLYMERASE; S-PHASE; RETINOBLASTOMA PROTEIN; TRANSFORMED-CELLS; CDK2 INHIBITION; PHOSPHORYLATION; GROWTH; DEATH AB Selective cyclin-dependent kinase (cdk) 2 inhibition is readily compensated. However, reduced cdk2 activity may have antiproliferative effects in concert with other family members. Here, inducible RNA interference was used to codeplete cdk2 and cdk1 from NCI-H1299 non-small cell lung cancer and U20S osteosarcoma cells, and effects were compared with those mediated by depletion of either cdk alone. Depletion of cdk2 slowed G(1) progression of NCI-H1299 cells and depletion of cdkI slowed G(2)-M progression in both cell lines, with associated endoreduplication in U20S cells. However, compared with the incomplete cell cycle blocks produced by individual depletion, combined depletion had substantial consequences, with G(2)-M arrest predominating in NCI-HI299 cells and apoptosis the primary outcome in U20S cells. In U20S cells, combined depletion affected RNA polymerase II expression and phosphorylation, causing decreased expression of the antiapoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis (XLAP), effects usually mediated by inhibition of the transcriptional cdk9. These events do not occur after individuaI depletion of cdk2 and cdk1, suggesting that reduction of cdk2, cdki, and RNA polymerase II activities all contribute to apoptosis in U2OS cells. The limited cell death induced by combined depletion in NCI-H1299 cells was significantly increased by codepletion of cdk9 or XILAP or by simultaneous treatment with the cdk9 inhibitor flavopiridol. These results show the potency of concomitant compromise of cell cycle and transcriptional cdk activities and may guide the selection of clinical drug candidates. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NCI NIH HHS [R01 CA090687] NR 42 TC 99 Z9 100 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2006 VL 66 IS 18 BP 9270 EP 9280 DI 10.1158/0008-5472.CAN-06-1758 PG 11 WC Oncology SC Oncology GA 086CI UT WOS:000240650300045 PM 16982772 ER PT J AU Ji, HB Sharpless, NE Wong, KK AF Ji, Hongbin Sharpless, Norman E. Wong, Kwok-Kin TI EGFR targeted therapy - View from biological standpoint SO CELL CYCLE LA English DT Article DE wt EGFR; EGFR mutant; wt EGFR targeted therapy; EGFR mutant targeted therapy; cell growth; cell survival; apoptosis ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; GENE-MUTATIONS; GEFITINIB SENSITIVITY; AKT PHOSPHORYLATION; NEVER SMOKERS; ERLOTINIB; ADENOCARCINOMAS AB Activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancers (NSCLCs) correlate with responsiveness to EGFR kinase inhibitors. In vitro cell culture studies have demonstrated that EGFR kinase domain mutants but not wild type (wt) EGFR are transforming and essential for cancer cell survival. We and others have recently demonstrated that the induction of EGFR kinase domain mutants specifically in murine lung epithelium in vivo led to development of adenocarcinoma with bronchioloalveolar carcinoma (BAC) features. These tumors depend completely on the sustained expression of EGFR kinase domain mutants for tumor maintenance. The murine tumors with EGFR kinase domain mutations are sensitive to EGFR targeted therapy similarly to NSCLC patients whose tumors harbor EGFR mutations. In contrast, initial results suggest that overexpression of wt EGFR in murine lungs does not seem to be transforming. We therefore divide EGFR targeted therapy in NSCLC patients into two parts: "EGFR mutant targeted therapy" and "wt EGFR targeted therapy". The "EGFR mutant targeted therapy" targets the oncogene essential for tumor initiation and maintenance and is frequently correlated with effective clinical outcome. In contrast, "wt EGFR targeted therapy" likely targets the proto-oncogene product wt EGFR, which is not directly involved in tumor initiation and maintenance, and in these cases, the response has been considerably less dramatic. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Ludwig Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Lowe Ctr Thorac Oncol, 44 Binney St,D810, Boston, MA 02115 USA. EM Kwong1@partners.org FU NCI NIH HHS [CA90679]; NIA NIH HHS [AG24004] NR 45 TC 13 Z9 15 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2006 VL 5 IS 18 BP 2072 EP 2076 DI 10.4161/cc.5.18.3277 PG 5 WC Cell Biology SC Cell Biology GA 089EC UT WOS:000240862100007 PM 16969107 ER PT J AU Lee, YM Sicinski, P AF Lee, Young-Mi Sicinski, Piotr TI Targeting cyclins and cyclin-dependent kinases in cancer - Lessons from mice, hopes for therapeutic applications in human SO CELL CYCLE LA English DT Review DE cyclins; cyclin-dependent kinases; mouse knockouts; chemical inhibitors; cancer ID PHASE-I TRIAL; CELL-CYCLE; PROTEIN-KINASE; CDK4; D1; INHIBITORS; PROLIFERATION; ANTISENSE; GROWTH; VIVO AB The activity of cyclins and their associated cyclin-dependent kinases (CDKs) is frequently deranged in human cancers. For this reason, cyclin-CDK complexes have been considered as very promising therapeutic targets in human malignancies. An obvious concern, however, is whether blocking cyclin-CDK function would preferentially affect cancer cells, but not normal, non-transformed cells. Two recent reports addressed the requirement for cyclin D1-CDK4 kinase in mouse development versus in neoplasia. These studies documented that the kinase activity of cyclin D1-CDK complexes is largely dispensable for normal development, but it is critically required for the initiation and maintenance of mammary carcinomas. Here we summarize the lessons learned from mouse knockout experiments, and discuss the utility of CDK inhibitors in therapy of human cancers, and possibly of other diseases. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [CA083688, CA108420] NR 62 TC 63 Z9 64 U1 1 U2 4 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2006 VL 5 IS 18 BP 2110 EP 2114 DI 10.4161/cc.5.18.3218 PG 5 WC Cell Biology SC Cell Biology GA 089EC UT WOS:000240862100012 PM 16969111 ER PT J AU Appleman, LJ Chernova, I Li, LQ Boussiotis, VA AF Appleman, Leonard J. Chernova, Irene Li, Lequn Boussiotis, Vassiliki A. TI CD28 costimulation mediates transcription of SKP2 and CKS1, the substrate recognition components of SCFSkp2 ubiquitin ligase that leads p27(kip1) to degradation SO CELL CYCLE LA English DT Article DE T lymphocytes; costimulation; cellular proliferation ID F-BOX PROTEIN; CELL-CYCLE PROGRESSION; KINASE INHIBITOR P27(KIP1); CDK INHIBITOR; PROSTATE-CANCER; DOWN-REGULATION; BREAST-CANCER; TGF-BETA; T-CELLS; P27 AB Activation through TCR/CD3-plus-CD28 induces primary T lymphocytes to enter S phase. Downregulation of cyclin-dependent kinase inhibitor p27(kip1) is critical in this process and is mediated by ubiquitin-targeted degradation of p27(kip1). Ubiquitination of p27(kip1) is performed by the SCFskp2 ubiquitin ligase comprised of the core components Roc1, Cul1 and Skp1 and the substrate recognition components Skp2 and Cks1. Here we show that in primary human T lymphocytes, the SCFskp2 core components Roc1, Cul1 and Skp1 are constitutively expressed, and their levels remain unchanged upon TCR/CD3-plus-CD28 costimulation. In contrast, the substrate recognition components Skp2 and Cks1 are almost undetectable in resting T cells and are transcriptionally induced upon costimulation. We determined that the SKP2 promoter lies directly upstream of the translational start site and contains binding sites for SP1, Elk-1 and E2F transcription factors. Mutagenesis of SP1 and Elk-1 sites abrogated TCR/CD3-plus-CD28-mediated SKP2 promoter-driven reporter activity, whereas mutagenesis of an E2F site enhanced reporter activity, suggesting that SKP2 promoter may act as a node of integration for mitogenic and anti-mitogenic signals. Thus, in primary T lymphocytes CD28 costimulation can directly regulate cell cycle progression by inducing transcription of the substrate recognition components of SCFskp2 ubiquitin ligase that targets p27(kip1) for degradation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02129 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol,Dana Farber Canc Inst, Room CNY 149-5106 13th St, Boston, MA 02129 USA. EM vboussiotis@partners.org OI Appleman, Leonard/0000-0003-4951-7388 FU NIAID NIH HHS [AI 46548, AI 043552] NR 46 TC 20 Z9 20 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2006 VL 5 IS 18 BP 2123 EP 2129 DI 10.4161/cc.5.18.3139 PG 7 WC Cell Biology SC Cell Biology GA 089EC UT WOS:000240862100014 PM 16969077 ER PT J AU Zorn, E Ritz, J AF Zorn, Emmanuel Ritz, Jerome TI Studying human regulatory T cells in vivo SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID VERSUS-HOST-DISEASE; DEFECTIVE SUPPRESSOR FUNCTION; BONE-MARROW-TRANSPLANTATION; PERIPHERAL-BLOOD; FOXP3; INTERLEUKIN-2; EXPRESSION; LYMPHOCYTES; HOMEOSTASIS; INDUCTION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu NR 37 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2006 VL 12 IS 18 BP 5265 EP 5267 DI 10.1158/1078-0432.CCR-06-1417 PG 3 WC Oncology SC Oncology GA 087AK UT WOS:000240714400005 PM 17000657 ER PT J AU Heist, RS Marshall, AL Liu, G Zhou, W Su, L Neuberg, D Lynch, TJ Wain, J Christiani, DC AF Heist, Rebecca Suk Marshall, Ariela L. Liu, Geoffrey Zhou, Wei Su, Li Neuberg, Donna Lynch, Thomas J. Wain, John Christiani, David C. TI Matrix metalloproteinase polymorphisms and survival in stage I non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; GENE-EXPRESSION; BREAST-CANCER; PROMOTER; MATRIX-METALLOPROTEINASE-9; SUSCEPTIBILITY; RISK; ADENOCARCINOMA; PROGRESSION; HAPLOTYPES AB Purpose: The matrix metalloproteinases (MMP) are a family of enzymes that can degrade extracellular matrix and facilitate invasion through the basement membrane. Several polymorphisms in MMP-1, MMP-2, MMP-3, and MMP-12 have been described, some of which lead to differential transcription. We hypothesized that polymorphisms in these MMP genes may be associated with survival outcomes in early-stage non-small cell lung cancer (NSCLC). Experimental Design: We evaluated the relationship between MMP-1 MMP-2 MMP-3, and MMP-12 polymorphisms and both recurrence-free survival (RFS) and overall survival (OS) among 382 patients with stage I NSCLC. Analyses of genotype associations with survival outcomes were done using Cox proportional hazards models and Kaplan-Meier methods and the log-rank test. Results: Patients carrying the variant G allele of the MMP-12 1082A/G polymorphism had significantly worse outcomes [crude hazard ratio (HR) for OS 1.74; 95% confidence interval (95% CI), 1.18-2.58, P = 0.006; crude HR for RFS, 1.53; 95% Cl, 1.05-2.23, P = 0.03]. After adjusting for age, sex, stage, pack-years of smoking, and histologic subtype, the MMP-12 1082A/G polymorphism remained significantly associated with survival outcomes [adjusted HR (AHR) for OS, 1.94; 95% Cl, 1.28-2.97, P = 0.002; AHR for RFS, 1.61; 95% Cl, 1.07-2.41, P = 0.02]. None of the other MMP polymorphisms was significantly associated with survival. Conclusions: Our results show that patients with stage I NSCLC carrying the variant G allele of the MMP-12 1082A/G polymorphism have worse survival. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Bldg 1,Room 1407,665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA 092824, ES/CA 06409, CA090578, CA074386] NR 33 TC 27 Z9 29 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2006 VL 12 IS 18 BP 5448 EP 5453 DI 10.1158/1078-0432.CCR-06-0262 PG 6 WC Oncology SC Oncology GA 087AK UT WOS:000240714400029 PM 17000679 ER PT J AU Luong, QT O'Kelly, J Braunstein, GD Hershman, JM Koeffler, HP AF Luong, Quang T. O'Kelly, James Braunstein, Glenn D. Hershman, Jerome M. Koeffler, H. Phillip TI Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE-DEACETYLASE INHIBITORS; ANTICANCER AGENTS; DNA METHYLATION; CARCINOMA; APOPTOSIS; DIFFERENTIATION; PROLIFERATION AB Purpose: The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has multiple antitumor effects against a variety of human cancers. Experimental design: We treated several anaplastic and papillary thyroid cancer cell lines with SAHA to determine if it could inhibit the growth of these cells in vitro and in vivo. Results: SAHA effectively inhibited 50% clonal growth of the anaplastic thyroid cancer cell lines, ARO and FRO, and the papillary thyroid cancer cell line, BHP 7-13, at 1.3 X 10(-7) to 5 X 10(-7) mol/L, doses that are achievable in patients. In concert with growth inhibition, SAHA down-regulated the expression of cyclin D1 and up-regulated levels of p21(WAF1). Annexin V and cleavage of poly(ADP)ribose polymerase were both increased by exposure of the thyroid cancer cells to SAHA. Expression of the death receptor 5 (DR5) gene was also increased by SAHA, but the combination of the DR5 ligand, tumor necrosis factor-related a poptosis-inducing ligand (TRAIL), with SAHA had little effect compared with SAHA alone. Of note, the combination of paclitaxel, doxorubicin, or paraplatin with SAHA enhanced cell killing of the thyroid cancer cells. In addition, murine studies showed that SAHA administered daily by i.p. injection at 100 mg/kg inhibited the growth of human thyroid tumor cells. Conclusion: Our data indicate that SAHA is a plausible adjuvant therapy for thyroid cancers. C1 Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Dept Med,Div Hematol Oncol, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol & Diabet, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Luong, QT (reprint author), Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Dept Med,Div Hematol Oncol, 8700 Beverly Blvd,Davis Bldg,Room 5022, Los Angeles, CA 90048 USA. EM trong.luong@gmail.com RI Luong, Quang/C-3253-2015 NR 24 TC 67 Z9 75 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2006 VL 12 IS 18 BP 5570 EP 5577 DI 10.1158/1078-0432.CCR-06-0367 PG 8 WC Oncology SC Oncology GA 087AK UT WOS:000240714400044 PM 17000694 ER PT J AU Preffer, F Dombkowski, D Dubrovsky, T Dorn, M Quagliaroli, R Leahy, K Duckett, L Ziganti, S AF Preffer, Frederic Dombkowski, David Dubrovsky, Tim Dorn, Michelle Quagliaroli, Robert Leahy, Kate Duckett, Larry Ziganti, Steven TI The use of polychromatic flow cytometry in diagnostic hematopathology SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 21st Annual Meeting of the Clinical-Cytometry-Society CY OCT 08-10, 2006 CL Long Beach, CA SP Clin Cytometry Soc C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP 15 PY 2006 VL 70B IS 5 MA 29 BP 374 EP 374 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 090TG UT WOS:000240974000036 ER PT J AU Li, XG Xiong, JW Shelley, CS Park, HY Arnaout, MA AF Li, Xiangen Xiong, Jing-Wei Shelley, C. Simon Park, Heiyoung Arnaout, M. Amin TI The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells SO DEVELOPMENT LA English DT Article DE hematopoiesis; angiogenesis; ZBP-89 gene; SCL/tal-1 gene; stem cells ID VASCULAR DEVELOPMENT; ENDOTHELIAL-CELLS; MYELOID-LEUKEMIA; COMMON PRECURSOR; BLOOD FORMATION; PROTEIN LMO2; MICE LACKING; DNA-BINDING; GENE; SCL AB Hematopoietic development is closely linked to that of blood vessels and the two processes are regulated in large part by transcription factors that control cell fate decisions and cellular differentiation. Both blood and blood vessels derive from a common progenitor, termed the hemangioblast, but the factor(s) specifying the development and differentiation of this stem cell population into the hematopoietic and vascular lineages remain ill defined. Here, we report that knockdown of the Kruppel- like transcription factor ZBP-89 in zebrafish embryos results in a bloodless phenotype, caused by disruption of both primitive and definitive hematopoiesis, while leaving primary blood vessel formation intact. Injection of ZBP-89 mRNA into cloche zebrafish embryos, which lack both the hematopoietic and endothelial lineages, rescues hematopoiesis but not vasculogenesis. Injection of mRNA for Stem Cell Leukemia (SCL), a transcription factor that directs hemangioblast development into blood cell precursors, rescues the bloodless phenotype in ZBP-89 zebrafish morphants. Forced expression of ZBP-89 induces the expansion of hematopoietic progenitors in wildtype zebrafish and in mouse embryonic stem cell cultures but inhibits angiogenesis in vivo and in vitro. These findings establish a unique regulatory role for ZBP-89, positioned at the interface between early blood and blood vessel development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nephrol Div, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nephrol Div, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu RI Xiong, Jing-Wei/A-7113-2011 FU NIA NIH HHS [K01 AG019676-04, AG19676]; NIDDK NIH HHS [R01 DK081920] NR 61 TC 22 Z9 26 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 15 PY 2006 VL 133 IS 18 BP 3641 EP 3650 DI 10.1242/dev.02540 PG 10 WC Developmental Biology SC Developmental Biology GA 077RC UT WOS:000240046500015 PM 16914492 ER PT J AU Xu, YW Wang, S Zhang, H Zhao, AZ Stanger, BZ Gu, GQ AF Xu, Yanwen Wang, Sui Zhang, Ha Zhao, Aizhen Stanger, Ben Z. Gu, Guoqiang TI The fringe molecules induce endocrine differentiation in embryonic endoderm. by activating cMyt1/cMyt3 SO DEVELOPMENTAL BIOLOGY LA English DT Article DE notch; manic fringe; Myt1; islet; pancreas; Ngn3 ID PANCREATIC DEVELOPMENT; CELL DIFFERENTIATION; LUNATIC-FRINGE; NOTCH PATHWAY; BETA-CELLS; TRANSCRIPTION FACTORS; GENE-EXPRESSION; ZINC-FINGER; ISLET-CELL; MICE AB Endocrine differentiation in the early embryonic pancreas is regulated by Notch signaling. Activated Notch signaling maintains pancreatic progenitor cells in an undifferentiated state, whereas suppression of Notch leads to endocrine cell differentiation. Yet it is not known what mechanism is employed to inactivate Notch in a correct number of precursor cells to balance progenitor proliferation and differentiation. We report that an established Notch modifier, Manic Fringe (Mfng), is expressed in the putative endocrine progenitors, but not in exocrine pancreatic tissues, during early islet differentiation. Using chicken embryonic endoderm as an assaying system, we found that ectopic Mfng expression is sufficient to induce endodermal cells to differentiate towards an endocrine fate. This endocrine-inducing activity depends on inactivation of Notch. Furthermore, ectopic Mfng expression induces the expression of basic helix-loop-helix gene, Ngn3, and two zinc finger genes, cMyt1 and cMyt3. These results suggest that Mfng-mediated repression of Notch signaling could serve as a trigger for endocrine islet differentiation. (c) 2006 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Program Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. RP Gu, GQ (reprint author), Vanderbilt Univ, Program Dev Biol, 221 Kirkland Hall, Nashville, TN 37232 USA. EM Guoqiang.gu@vanderbilt.edu RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NIDDK NIH HHS [2R01 DK065949-01A1, DK20593] NR 67 TC 18 Z9 19 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2006 VL 297 IS 2 BP 340 EP 349 DI 10.1016/j.ydbio.2006.04.456 PG 10 WC Developmental Biology SC Developmental Biology GA 088UH UT WOS:000240836100004 PM 16920096 ER PT J AU Arima, T Hata, K Tanaka, S Kusumi, M Li, E Kato, K Shiota, K Sasaki, H Wake, N AF Arima, Takahiro Hata, Kenichiro Tanaka, Satoshi Kusumi, Maki Li, En Kato, Kiyoko Shiota, Kunio Sasaki, Hiroyuki Wake, Norio TI Loss of the maternal imprint in Dnmt3L(mat-/-) mice leads to a differentiation defect in the extraembryonic tissue SO DEVELOPMENTAL BIOLOGY LA English DT Article DE genomic imprinting; TS (trophoblastic stem) cells; differentiation; Dnmt3L ID DE-NOVO METHYLATION; MAMMALIAN DEVELOPMENT; DNA METHYLATION; DNMT3L; GENE; METHYLTRANSFERASES; PLACENTA; CLONING; FAMILY; EXPRESSION AB DNA methylation of the genome is essential for mammalian development and plays crucial roles in a variety of biological processes including genomic imprinting. Although the DNA methyltransferase 3-like (Dnmt3L) protein lacks DNA methylase activity, it is thought to establish the maternal imprint in combination with the functional DNA methyltransferases. Oogenesis apparently proceeds normally in female mice homozygous for a targeted deletion of Dnmt3L, but their heterozygous offspring (Dnmt3Lmat(-/-)) die before midgestation due to an imprinting defect. In this study, we show that Dnmt3L is required for the establishment of maternal methylation imprints both in the embryos and the placentae and that the placentae of these embryos develop abnormally. There is a defect in the formation of the labyrinth, reduced formation of the spongiotrophoblast layer, excess trophoblast giant cells and insufficient attachment between the chorion layer and the ectoplacental cone. In addition, we demonstrate arrest of proliferation of the extraembryonic tissue without apoptosis in vivo and a disturbance of the cell fate of Dnmt3L(mat-/-) trophoblastic stem cells in vitro. Furthermore, we report that DNA methylation during oogenesis is essential for the establishment of imprinting Mash2. These findings provide evidence that not only is DNA methylation required for the appropriate maternal imprint in the placenta but that the appropriate imprint is absolutely required for vertebrate placentation. (c) 2006 Elsevier Inc. All rights reserved. C1 Kyushu Univ, Dept Mol Genet, Div Mol & Cell Therapeut, Med Inst Bioregulat, Oita 8740838, Japan. Res Org Informat & Syst, Div Human Genet, Dept Integrated Genet, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. Grad Univ Adv Studies, Dept Genet, Sch Life Sci, SOKENDAI, Mishima, Shizuoka 4118540, Japan. Univ Tokyo, Lab Cellular Biochem, Dept Anim Resource Sci Vet Med Sci, Tokyo, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Arima, T (reprint author), Kyushu Univ, Dept Mol Genet, Div Mol & Cell Therapeut, Med Inst Bioregulat, Oita 8740838, Japan. EM tarima@tsurumi.beppu.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 NR 42 TC 55 Z9 61 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2006 VL 297 IS 2 BP 361 EP 373 DI 10.1016/j.ydbio.2006.05.003 PG 13 WC Developmental Biology SC Developmental Biology GA 088UH UT WOS:000240836100006 PM 16920095 ER PT J AU Verdier, V Johndrow, JE Betson, M Chen, GC Hughes, DA Parkhurst, SM Settleman, J AF Verdier, Valerie Johndrow, James E. Betson, Martha Chen, Guang-Chao Hughes, David A. Parkhurst, Susan M. Settleman, Jeffrey TI Drosophila Rho-kinase (DRok) is required for tissue morphogenesis in diverse compartments of the egg chamber during oogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE oogenesis; Rho-kinase; actin; moesin; cytoskeleton; Drosophila ID ALPHA-LIKE PROTEIN; MYOSIN PHOSPHATASE; IN-VIVO; ACTIN CYTOSKELETON; ERM PROTEINS; LIM-KINASE; AXIS SPECIFICATION; SIGNALING PATHWAY; BINDING KINASE; FAMILY GTPASES AB The Rho-kinases are widely utilized downstream targets of the activated Rho GTPase that have been directly implicated in many aspects of Rho-dependent effects on F-actin assembly, acto-myosin contractility, and microtubule stability, and consequently play an essential role in regulating cell shape, migration, polarity, and division. We have determined that the single closely related Drosophila Rho-kinase ortholog, DRok, is required for several aspects of oogenesis, including maintaining the integrity of the oocyte cortex, actin-mediated tethering of nurse cell nuclei, "dumping" of nurse cell contents into the oocyte, establishment of oocyte polarity, and the trafficking of oocyte yolk granules. These defects are associated with abnormalities in DRok-dependent actin dynamics and appear to be mediated by multiple downstream effectors of activated DRok that have previously been implicated in oogenesis. DRok regulates at least one of these targets, the membrane cytoskeletal cross-linker DMoesin, via a direct phosphorylation that is required to promote localization of DMoesin to the oocyte cortex. The collective oogenesis defects associated with DRok deficiency reveal its essential role in multiple aspects of proper oocyte formation and suggest that DRok defines a novel class of oogenesis determinants that function as key regulators of several distinct actin-dependent processes required for proper tissue morphogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Univ Manchester, Fac Life Sci, Manchester, Lancs, England. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu RI Betson, Martha/D-3818-2014; OI Betson, Martha/0000-0002-4220-3290; Parkhurst, Susan/0000-0001-5806-9930 FU NCI NIH HHS [R01 CA062142-13]; NIGMS NIH HHS [R01 GM060466, R01 GM066847, R01 GM60466] NR 69 TC 10 Z9 12 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2006 VL 297 IS 2 BP 417 EP 432 DI 10.1016/j.ydbio.2006.05.016 PG 16 WC Developmental Biology SC Developmental Biology GA 088UH UT WOS:000240836100010 PM 16887114 ER PT J AU Eeckhoute, J Carroll, JS Geistlinger, TR Torres-Arzayus, MI Brown, M AF Eeckhoute, Jerome Carroll, Jason S. Geistlinger, Timothy R. Torres-Arzayus, Maria I. Brown, Myles TI A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer SO GENES & DEVELOPMENT LA English DT Article DE breast cancer; estrogen receptor; cyclin D1; transcription; enhancer; chromatin ID MAMMARY-GLAND DEVELOPMENT; D-1 GENE-TRANSCRIPTION; RECEPTOR-ALPHA; GROWTH-FACTOR; C-MYC; EXPRESSION; ACTIVATION; CHROMATIN; PROMOTER; COMPLEX AB Estrogen stimulates the proliferation of the most common type of human breast cancer that expresses estrogen receptor alpha(ER alpha) through the activation of the cyclin D1 (CCND1) oncogene. However, our knowledge of ER alpha transcriptional mechanisms remains limited. Hence, it is still elusive why ER alpha ectopically expressed in ER-negative breast cancer cells (BCC) is functional on ectopic reporter constructs but lacks activity on many endogenous target genes, including CCND1. Here, we show that estradiol (E2) stimulation of CCND1 expression in BCC depends on a novel cell-type-specific enhancer downstream from the CCND1 coding region, which is the primary ER alpha recruitment site in estrogen-responsive cells. The pioneer factor FoxA1 is specifically required for the active chromatin state of this enhancer and as such is crucial for both CCND1 expression and subsequent cell cycle progression. Interestingly, even in BCC, CCND1 levels and proliferation are tightly controlled by E2 through the establishment of a negative feedforward loop involving the induction of NFIC, a putative tumor suppressor capable of directly repressing CCND1 transcription. Taken together, our results reveal an estrogen-regulated combinatorial network including cell-specific cis- and trans-regulators of CCND1 expression where ER alpha collaborates with other transcription factors associated with the ER-positive breast cancer phenotype, including FoxA1 and NFIC. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 FU NCI NIH HHS [P01 CA080111, P01 CA80111]; NIDDK NIH HHS [R56 DK074967] NR 61 TC 164 Z9 169 U1 0 U2 5 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 SEP 15 PY 2006 VL 20 IS 18 BP 2513 EP 2526 DI 10.1101/gad.1446006 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 084IN UT WOS:000240526700005 PM 16980581 ER PT J AU Shi, GB Boyle, SC Sparrow, DB Dunwoodie, SL Shioda, T de Caestecker, MP AF Shi, Genbin Boyle, Scott C. Sparrow, Duncan B. Dunwoodie, Sally L. Shioda, Toshi de Caestecker, Mark P. TI The transcriptional activity of CITED1 is regulated by phosphorylation in a cell cycle-dependent manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; NUCLEAR-PROTEIN; BINDING-PROTEIN; MSG1; FAMILY; DOMAIN; MEMBER; MRG1; RICH; TRANSACTIVATION AB CITED1 is the founding member of the CITED family of cofactors that are involved in regulating a wide variety of CBP/p300-dependent transcriptional responses. In the present study, we show that the phosphorylation status of CITED1 changes during the cell cycle and affects its transcriptional cofactor activity. Tryptic mapping and mutagenesis studies identified five phosphorylated serine residues in CITED1. Phosphorylation of these residues did not affect CRM1-dependent nuclear export, but did decrease CITED1 binding to p300 and inhibited CITED1-dependent transactivation of Smad4 and p300. These results suggest that CITED1 functions as a cell cycle-dependent transcriptional cofactor whose activity is regulated by phosphorylation. C1 Vanderbilt Univ, Med Ctr, Div Nephrol, Sch Med,Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA 02129 USA. Univ New S Wales, Victor Chang Cardiac Res Inst, Sydney, NSW 2010, Australia. RP de Caestecker, MP (reprint author), Vanderbilt Univ, Med Ctr, Div Nephrol, Sch Med,Dept Med, S-3223,Med Ctr N,1161 21st St S, Nashville, TN 37232 USA. EM Mark.de.Caestecker@vanderbilt.edu RI Sparrow, Duncan/B-3994-2008; OI Sparrow, Duncan/0000-0002-1141-6613; Dunwoodie, Sally/0000-0002-2069-7349 FU NIDDK NIH HHS [R01DK61558] NR 36 TC 13 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 2006 VL 281 IS 37 BP 27426 EP 27435 DI 10.1074/jbc.M602631200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082PB UT WOS:000240397700069 PM 16864582 ER PT J AU Yeo, Y Burdick, JA Highley, CB Marini, R Langer, R Kohane, DS AF Yeo, Yoon Burdick, Jason A. Highley, Christopher B. Marini, Robert Langer, Robert Kohane, Daniel S. TI Peritoneal application of chitosan and UV-cross-linkable chitosan SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE chitosan; UV-cross-linkable; peritoneum; adhesion; biocompatibility ID POSTSURGICAL ADHESION FORMATION; N-ACETYLATED CHITOSANS; PHOTOCROSSLINKABLE CHITOSAN; IN-VITRO; DEGRADATION; PREVENTION; MICE; HYDROGEL; DELIVERY; SCAFFOLD AB The suitability of chitosan and UV-cross-linkable chitosan for intraperitoneal use, for example as a barrier device for preventing peritoneal adhesions or for drug delivery, was examined. In vitro experiments using two major cell types present in the peritoneal cavity (mesothelial cells and peritoneal macrophages) revealed neither attractive interactions between cross-linked chitosan gels and the cells nor a proliferative effect. However, the same UV-cross-linked chitosan applied in the peritoneal cavity of rabbits caused a granulomatous reaction with adhesion formation within two weeks in all animals, which persisted up to 4 weeks after exposure. Unmodified chitosan also caused adhesions, while UV irradiation did not. UV-cross-finkable chitosan induced significant elevations in MIP-2 and TNF-alpha from peritoneal macrophages, suggesting that soluble mediators could play a role in inducing adhesion formation. These results reinforce the view that the predictive value of in vitro cytotoxicity assays in matters of biocompatibility may not be sufficient, and suggest that other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. in vivo). (c) 2006 Wiley Periodicals, Inc. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. RP Kohane, DS (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave,E25-342, Cambridge, MA 02139 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM073626] NR 33 TC 37 Z9 38 U1 0 U2 20 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD SEP 15 PY 2006 VL 78A IS 4 BP 668 EP 675 DI 10.1002/jbm.a.30740 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 076BU UT WOS:000239932800003 PM 16739173 ER PT J AU Bhattacharjee, A Xu, B Frank, DA Feldman, GM Cathcart, MK AF Bhattacharjee, Ashish Xu, Bo Frank, David A. Feldman, Gerald M. Cathcart, Martha K. TI Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling complex with protein kinase C delta and tyrosine-phosphorylated Stat3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID 15-LIPOXYGENASE GENE-EXPRESSION; CENTRIFUGAL ELUTRIATION CCE; MONOCYTE-ENRICHED FRACTIONS; MONONUCLEAR CELL SUBSETS; LOW-DENSITY-LIPOPROTEIN; SERINE PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVATION; ATHEROSCLEROTIC LESIONS; RECEPTOR COMPONENTS; ENDOTHELIAL-CELLS AB Our previous studies demonstrated that the IL-13-induced 15-lipoxygenase expression in primary human monocytes is regulated by the activation of both Stat1 and Stat3 and by protein kinase C (PKC)delta. IL-13 stimulated the phosphorylation of Stat3 on both Tyr(705) and Ser(727). In this study we show that IL-13 induces the association of PKCS with Stat3, not with Stall, and is required for Stat3 Ser 727 phosphorylation. We found a novel IL-13-dependent cytosolic signaling complex of PKCS and tyrosine-phosphorylated Stat3. A tyrosine kinase inhibitor blocked PKC delta association with Stat3 as well as Stat3 Ser 727 phosphorylation. We therefore hypothesized that tyrosine phosphorylation was required for Stat3 interaction with PKC delta and subsequent PKC delta-5-dependent phosphorylation of Stat3 Ser(727). We developed an efficient transfection protocol for human monocytes. Expression of Stat3 containing a mutation in Tyr(705) inhibited the association of PKC5 with Stat3 and blocked Stat3 Ser 727 phosphorylation, whereas transfection with wild-type Stat3 did not. Furthermore, by transfecting monocytes with Stat3 containing mutations in Tyr(705) or Ser(727) or with wild-type Stat3, we demonstrated that both Stat3 tyrosine and serine phosphorylations are required for optimal binding of Stat3 with DNA and maximal expression of 15-lipoxygenase, an important regulator of inflammation and apoptosis. C1 Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA. Case Western Reserve Univ, Dept Mol Med, Lerner Coll Med, Cleveland Clin, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cathcart, MK (reprint author), Cleveland Clin Fdn, Dept Cell Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM cathcam@ccf.org FU NCRR NIH HHS [M01 RR-018390]; NHLBI NIH HHS [HL51068] NR 55 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2006 VL 177 IS 6 BP 3771 EP 3781 PG 11 WC Immunology SC Immunology GA 083RG UT WOS:000240475300031 PM 16951338 ER PT J AU Karni, A Abraham, M Monsonego, A Cai, GF Freeman, GJ Hafler, D Khoury, SJ Weiner, HL AF Karni, Arnon Abraham, Michal Monsonego, Alon Cai, Guifang Freeman, Gordon J. Hafler, David Khoury, Samia J. Weiner, Howard L. TI Innate immunity in multiple sclerosis: Myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CD40-CD40 LIGAND INTERACTIONS; MYELIN BASIC-PROTEIN; PERIPHERAL-BLOOD; CD40 LIGAND; IFN-GAMMA; INTERFERON; INDUCTION; DISEASE AB Multiple sclerosis (MS) is postulated to be a T cell-mediated autoimmune disease characterized clinically by a relapsing-remitting (RR) stage followed by a secondary progressive (SP) phase. The progressive phase is felt to be secondary to neuronal degenerative changes triggered by inflammation. The status of the innate immune system and its relationship to the stages of MS is not well understood. Dendritic cells (DCs) are professional APCs that are central cells of the innate immune system and have the unique capacity to induce primary immune responses. We investigated circulating myeloid DCs isolated directly from the blood to determine whether there were abnormalities in myeloid DCs in MS and whether they were related to disease stage. We found that SP-MS subjects had an increased percentage of DCs expressing CD80, a decreased percentage expressing PD-L1, and an increased percentage producing IL-12 and TNF-alpha compared with RR-MS or controls. A higher percentage of DCs from both RR and SP-MS patients expressed CD40 compared with controls. We then investigated the polarization effect of DCs from MS patients on naive T cells taken from cord blood using a MLR assay. Whereas DCs from RR-MS induced higher levels of Th1 (IFN-gamma, TNF-alpha) and Th2 (IL-4, IL-13) cytokines compared with controls, DCs from SP-MS only induced a polarized Th1 response. These results demonstrate abnormalities of DCs in MS and may explain the immunologic basis for the different stages and clinical patterns of MS. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Inst Med 730, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Sch Med, Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel. RP Weiner, HL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Inst Med 730, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM hweiner@rics.bwh.harvard.edu OI khoury, samia/0000-0003-3198-6063 FU NINDS NIH HHS [NS023132] NR 43 TC 90 Z9 92 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2006 VL 177 IS 6 BP 4196 EP 4202 PG 7 WC Immunology SC Immunology GA 083RG UT WOS:000240475300078 PM 16951385 ER PT J AU Streeck, H Jessen, H Alter, G Teigen, N Waring, MT Jessen, A Stahmer, I van Lunzen, J Lichterfeld, M Gao, XJ Allen, TM Carrington, M Walker, BD Rockstroh, JK Altfeld, M AF Streeck, Hendrik Jessen, Heiko Alter, Galit Teigen, Nickolas Waring, Mike T. Jessen, Arne Stahmer, Ingrid van Lunzen, Jan Lichterfeld, Mathias Gao, Xiaojiang Allen, Todd M. Carrington, Mary Walker, Bruce D. Rockstroh, Juergen K. Altfeld, Marcus TI Immunological and virological impact of highly active antiretroviral therapy initiated during acute HIV-1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-LYMPHOCYTES; DISCONTINUATION; CELLS; IDENTIFICATION; RESPONSES AB The immunological and virological impact of short-term treatment initiated during acute human immunodeficiency virus type 1 (HIV-1) infection was assessed prospectively in 20 subjects, 12 of whom initiated highly active antiretroviral therapy (HAART) for 24 weeks and then terminated treatment. Treatment resulted in suppression of viremia, an increase in the CD4(+) T cell count, enhanced differentiation of HIV-1-specific CD8(+) T cells from effector memory to effector cells at week 24 of HAART, and significantly higher virus-specific interferon-gamma(+) CD8(+) T cell responses after viral rebound (at week 48). However, despite these immunological changes, no differences in viremia or in the CD4(+) T cell count were found 6 months after HAART was stopped, when treated subjects were compared with untreated subjects. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Lab Genom Divers, Frederick, MD 21701 USA. Univ Hamburg, Hosp Eppendorf, Med Ctr, Infect Dis Unit, D-20246 Hamburg, Germany. Univ Bonn, Dept Internal Med, Bonn, Germany. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Bldg 149,13th St,6th Floor, Boston, MA 02129 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011 NR 15 TC 56 Z9 56 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2006 VL 194 IS 6 BP 734 EP 739 DI 10.1086/503811 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 081KN UT WOS:000240316600003 PM 16941338 ER PT J AU Guzman-Marin, R Ying, Z Suntsova, N Methippara, M Bashir, T Szymusiak, R Gomez-Pinilla, F McGinty, D AF Guzman-Marin, Ruben Ying, Zhe Suntsova, Natalia Methippara, Melvi Bashir, Tariq Szymusiak, Ronald Gomez-Pinilla, Fernando McGinty, Dennis TI Suppression of hippocampal plasticity-related gene expression by sleep deprivation in rats SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID LONG-TERM POTENTIATION; ELEMENT-BINDING-PROTEIN; LIGHT-DARK CYCLE; NEUROTROPHIC FACTOR; SYNAPTIC PLASTICITY; PARADOXICAL SLEEP; MESSENGER-RNAS; DENTATE GYRUS; GROWTH-FACTOR; BRAIN AB Previous work shows that sleep deprivation impairs hippocampal-dependent learning and long-term potentiation (LTP). Brain-derived neurotrophic factor (BDNF), cAMP response-element-binding (CREB) and calcium-calmodulin-dependent protein kinase II (CAMKII) are critical modulators of hippocampal-dependent learning and LTP. In the present study we compared the effects of short- (8 h) and intermediate-term (48 h) sleep deprivation (SD) on the expression of BDNF and its downstream targets, Synapsin I, CREB and CAMKII in the neocortex and the hippocampus. Rats were sleep deprived using an intermittent treadmill system which equated total movement in the SD and control treadmill animals (CT), but permitted sustained periods of rest in CT animals. Animals were divided into SD (treadmill schedule: 3 s on/12 s off) and two treadmill control groups, CT1 (15 min on/60 min off) and CT2 (30 min on/120 min off-permitting more sustained sleep). Real-time Taqman RT-PCR was used to measure changes in mRNA; BDNF protein levels were determined using ELISA. In the hippocampus, 8 h treatments reduced BDNF, Synapsin I, CREB and CAMKII gene expression in both SD and control groups. Following 48 h of experimental procedures, the expression of all these four molecular markers of plasticity was reduced in SD and CT1 groups compared to the CT2 and cage control groups. In the hippocampus, BDNF protein levels after 8 h and 48 h treatments paralleled the changes in mRNA. In neocortex, neither 8 h nor 48 h SD or control treatments had significant effects on BDNF, Synapsin I and CAMKII mRNA levels. Stepwise regression analysis suggested that loss of REM sleep underlies the effects of SD on hippocampal BDNF, Synapsin I and CREB mRNA levels, whereas loss of NREM sleep underlies the effects on CAMKII mRNA. C1 VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Injury Res Ctr, Div Neurosurg, Los Angeles, CA 90024 USA. Rostov State Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu 344006, Russia. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NHLBI NIH HHS [HL 60296, P50 HL060296]; NIMH NIH HHS [MH 47480, R01 MH047480] NR 58 TC 92 Z9 94 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 15 PY 2006 VL 575 IS 3 BP 807 EP 819 DI 10.1113/jphysiol.2006.115287 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 081XH UT WOS:000240350400013 PM 16825295 ER PT J AU Basmaciogullari, S Pacheco, B Bour, S Sodroski, J AF Basmaciogullari, Stephane Pacheco, Beatriz Bour, Stephan Sodroski, Joseph TI Specific interaction of CXCR4 with CD4 and CD8 alpha: Functional analysis of the CD4/CXCR4 interaction in the context of HIV-1 envelope glycoprotein-mediated membrane fusion SO VIROLOGY LA English DT Article DE CD4; CD8 alpha; CXCR4; membrane fusion; fusion inhibitors; HIV-1; immunological synapse ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYROSINE-PROTEIN-KINASE; TYPE-1 VPU PROTEIN; AMINO-TERMINAL DOMAIN; CHEMOKINE RECEPTOR; CYTOPLASMIC DOMAIN; T-LYMPHOCYTES; TETRASPAN MICRODOMAINS; CONFORMATIONAL-CHANGES; IMMUNOLOGICAL SYNAPSE AB We investigated possible interactions between HIV-1 receptor (CD4) and the main coreceptors CXCR4 and CCR5. We found that CD4 and CXCR4 coexpressed in 293T cells form a complex that can be immunoprecipitated with antibodies directed against the extracellular domain of either protein. Mutagenesis revealed that the CD4/CXCR4 interaction maps to two previously uncharacterized basic motifs in the cytoplasmic domain of CD4. HIV-1 envelope glycoprotein-mediated membrane fusion was found to be independent of the ability of CD4 and CXCR4 to interact, whether fusion was studied in a virus-cell or a cell-cell model. However, this interaction might explain the adaptation of HIV-1 to CXCR4 as an alternative to CCR5. We found that CXCR4 also interacts with the cytoplasmic domain of CD8 alpha in a way that is similar to the CD4/CXCR4 interaction. The CD4/CXCR4 and CD8 alpha/CXCR4 interactions may thus be involved in cellular signaling pathways shared by the CD4 and CD8 alpha molecules. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIAID, Off Technol Informat Syst, Bioinformat & Computat Biol Program, Bethesda, MD 20892 USA. RP Basmaciogullari, S (reprint author), Inst Cochin Genet Mol, Dept Malad Infect, Batiment Gustave Roussy,28 Rue Faubourg St Jacque, F-75014 Paris, France. EM basmaciogullari@cochin.inserm.fr NR 93 TC 14 Z9 14 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2006 VL 353 IS 1 BP 52 EP 67 DI 10.1016/j.virol.2006.05.027 PG 16 WC Virology SC Virology GA 084DL UT WOS:000240512100007 PM 16808956 ER PT J AU Javanbakht, H Yuan, W Yeung, DF Song, B Diaz-Griffero, F Li, Y Li, X Stremlau, M Sodroski, J AF Javanbakht, Hassan Yuan, Wen Yeung, Darwin F. Song, Byeongwoon Diaz-Griffero, Felipe Li, Yuan Li, Xing Stremlau, Matthew Sodroski, Joseph TI Characterization of TRIM5 alpha trimerization and its contribution to human immunodeficiency virus capsid binding SO VIROLOGY LA English DT Article DE TRIM5 alpha; HIV-1; retroviral capsid; coiled-coil domain; trimerization ID RESTRICTION FACTOR; COILED COILS; MONKEY TRIM5-ALPHA; HIV-1; MOTIF; RESISTANCE; INFECTION; TRIMERS; DOMAINS; TYPE-1 AB The coiled-coil domain of the tripartite motif (TRIM) family protein TRIM5 alpha is required for trimerization and function as an antiretroviral restriction factor. Unlike the coiled-coil regions of other related TRIM proteins, the coiled coil of TRIM5 alpha is not sufficient for multimerization. The linker region between the coiled-coil and B30.2 domains is necessary for efficient TRIM5 alpha trimerization. Most of the hydrophilic residues predicted to be located on the surface-exposed face of the coiled coil can be altered without compromising TRIM5 alpha antiviral activity against human immunodeficiency virus (HIV-1). However, changes that disrupt TRIM5 alpha trimerization proportionately affect the ability of TRIM5 alpha to bind HIV-1 capsid complexes. Therefore, TRIM5 alpha trimerization makes a major contribution to its avidity for the retroviral capsid, and to the ability to restrict virus infection. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Div AIDS, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Div AIDS, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Li, Yuan/B-4098-2013 FU NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI28691, AI063987, AI45405] NR 26 TC 90 Z9 97 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2006 VL 353 IS 1 BP 234 EP 246 DI 10.1016/j.virol.2006.05.017 PG 13 WC Virology SC Virology GA 084DL UT WOS:000240512100023 PM 16808955 ER PT J AU Prakriya, M Feske, S Gwack, Y Srikanth, S Rao, A Hogan, PG AF Prakriya, Murali Feske, Stefan Gwack, Yousang Srikanth, Sonal Rao, Anjana Hogan, Patrick G. TI Orai1 is an essential pore subunit of the CRAC channel SO NATURE LA English DT Article ID ACTIVATED CA2+ CHANNELS; T-LYMPHOCYTES; CALCIUM-CHANNELS; PLASMA-MEMBRANE; I-CRAC; STORE; SELECTIVITY; PERMEATION; CELLS; STIM1 AB Stimulation of immune cells causes depletion of Ca2+ from endoplasmic reticulum ( ER) stores, thereby triggering sustained Ca2+ entry through store-operated Ca2+ release-activated Ca2+ ( CRAC) channels, an essential signal for lymphocyte activation and proliferation(1,2). Recent evidence indicates that activation of CRAC current is initiated by STIM proteins, which sense ER Ca2+ levels through an EF-hand located in the ER lumen and relocalize upon store depletion into puncta closely associated with the plasma membrane(3-5). We and others recently identified Drosophila Orai and human Orai1 ( also called TMEM142A) as critical components of store- operated Ca2+ entry downstream of STIM6-8. Combined overexpression of Orai and Stim in Drosophila cells(8), or Orai1 and STIM1 in mammalian cells(9-11), leads to a marked increase in CRAC current. However, these experiments did not establish whether Orai is an essential intracellular link between STIM and the CRAC channel, an accessory protein in the plasma membrane, or an actual pore subunit. Here we show that Orai1 is a plasma membrane protein, and that CRAC channel function is sensitive to mutation of two conserved acidic residues in the transmembrane segments. E106D and E190Q substitutions in transmembrane helices 1 and 3, respectively, diminish Ca2+ influx, increase current carried by monovalent cations, and render the channel permeable to Cs+. These changes in ion selectivity provide strong evidence that Orai1 is a pore subunit of the CRAC channel. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, 200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu OI Feske, Stefan/0000-0001-5431-8178 NR 30 TC 684 Z9 698 U1 6 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 14 PY 2006 VL 443 IS 7108 BP 230 EP 233 DI 10.1038/nature05122 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 083OB UT WOS:000240467000051 PM 16921383 ER PT J AU Massberg, S von Andrian, UH AF Massberg, Steffen von Andrian, Ulrich H. TI Fingolimod and sphingosine-1-phosphate - Modifers of lymphocyte migration SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI von Andrian, Ulrich/A-5775-2008 NR 2 TC 80 Z9 83 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 14 PY 2006 VL 355 IS 11 BP 1088 EP 1091 DI 10.1056/NEJMp068159 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 083NJ UT WOS:000240462800003 PM 16971715 ER PT J AU Goldie, SJ Yazdanpanah, Y Losina, E Weinstein, MC Anglaret, X Walensky, RP Hsu, HE Kimmel, A Holmes, C Kaplan, JE Freedberg, KA AF Goldie, Sue J. Yazdanpanah, Yazdan Losina, Elena Weinstein, Milton C. Anglaret, Xavier Walensky, Rochelle P. Hsu, Heather E. Kimmel, April Holmes, Charles Kaplan, Jonathan E. Freedberg, Kenneth A. TI Cost-effectiveness of HIV treatment in resource-poor settings - The case of Cote d'Ivoire SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; SUB-SAHARAN AFRICA; HIV-1-INFECTED ADULTS; DEVELOPING-COUNTRIES; COTRIMOXAZOLE PROPHYLAXIS; VIROLOGICAL FAILURE; TRIMETHOPRIM-SULFAMETHOXAZOLE; VIRAL LOAD; INTERVENTIONS AB BACKGROUND: As antiretroviral therapy is increasingly used in settings with limited resources, key questions about the timing of treatment and use of diagnostic tests to guide clinical decisions must be addressed. METHODS: We assessed the cost-effectiveness of treatment strategies for a cohort of adults in Cote d'Ivoire who were infected with the human immunodeficiency virus (HIV) (mean age, 33 years; CD4 cell count, 331 per cubic millimeter; HIV RNA level, 5.3 log copies per milliliter). Using a computer-based simulation model that incorporates the CD4 cell count and HIV RNA level as predictors of disease progression, we compared the long-term clinical and economic outcomes associated with no treatment, trimethoprim-sulfamethoxazole prophylaxis alone, antiretroviral therapy alone, and prophylaxis with antiretroviral therapy. RESULTS: Undiscounted gains in life expectancy ranged from 10.7 months with antiretroviral therapy and prophylaxis initiated on the basis of clinical criteria to 45.9 months with antiretroviral therapy and prophylaxis initiated on the basis of CD4 testing and clinical criteria, as compared with trimethoprim-sulfamethoxazole prophylaxis alone. The incremental cost per year of life gained was $240 (in 2002 U.S. dollars) for prophylaxis alone, $620 for antiretroviral therapy and prophylaxis without CD4 testing, and $1,180 for antiretroviral therapy and prophylaxis with CD4 testing, each compared with the next least expensive strategy. None of the strategies that used antiretroviral therapy alone were as cost-effective as those that also used trimethoprim-sulfamethoxazole prophylaxis. Life expectancy was increased by 30% with use of a second line of antiretroviral therapy after failure of the first-line regimen. CONCLUSIONS: A strategy of trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy, with the use of clinical criteria alone or in combination with CD4 testing to guide the timing of treatment, is an economically attractive health investment in settings with limited resources. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA 02115 USA. Fac Med Lille, Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, F-59045 Lille, France. CNRS, URA 362, Lab Rech Econ & Sociales, Lille, France. Boston Univ, Sch Publ Hlth, Boston, MA USA. INSERM, U593, Bordeaux, France. Programme PAC CI, Abidjan, Cote Ivoire. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pittsburgh, Sch Med, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Goldie, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, 718 Huntington Ave,2nd Fl, Boston, MA 02115 USA. EM sue_goldie@harvard.edu RI Anglaret, Xavier/F-7333-2013 FU NIAID NIH HHS [K25 AI050436, K23 AI001794, K23-AI01794, K24 AI062476, K24-AI062476, K25-AI50436, R01 AI058736, R01-AI058736]; PHS HHS [U64/CCU 114927, U64/CCU 119525] NR 59 TC 189 Z9 194 U1 1 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 14 PY 2006 VL 355 IS 11 BP 1141 EP 1153 DI 10.1056/NEJMsa060247 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 083NJ UT WOS:000240462800008 PM 16971720 ER PT J AU McDougal, WS Tolkoff-Rubin, NE Michaelson, MD Mueller, PR Braaten, K AF McDougal, W. Scott Tolkoff-Rubin, Nina E. Michaelson, M. Dror Mueller, Peter R. Braaten, Kristina TI Case 28-2006: A 59-year-old man with masses in both kidneys - Renal-cell carcinoma, clear-cell type, involving both kidneys, with solitary metastasis to the right lung SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GUIDED RADIOFREQUENCY ABLATION; RADIO-FREQUENCY ABLATION; TUMORS C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Urol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 14 PY 2006 VL 355 IS 11 BP 1161 EP 1167 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 083NJ UT WOS:000240462800012 PM 16971723 ER PT J AU Brennan, FX Tieder, JB AF Brennan, Francis X. Tieder, J. Bernard, III TI Centrally administered tumor necrosis factor-alpha facilitates the avoidance performance of Sprague-Dawley rats SO BRAIN RESEARCH LA English DT Article DE escape/avoidance conditioning; tumor necrosis factor-alpha; anxiety; stress; coping ID BEHAVIORAL VARIATIONS; CENTRAL MONOAMINE; INTERLEUKIN-1-BETA; MEMORY; SENSITIZATION; BRAIN; CORTICOSTERONE; CYTOKINES AB In addition to their immunological functions, recent research has indicated that the proinflammatory cytokines can influence learning and memory processes. We have previously shown that a peripheral injection of TNF alpha facilitates the acquisition of a leverpress avoidance task 24 h post-injection. Because the improved acquisition is presumably mediated by central changes, the current experiment involved directly injecting TNF alpha into the third ventricle 24 h prior to training. The data indicate that low (20 ng) but not high (40 ng) doses of TNFa produced improved avoidance performance. Results are discussed in terms of possible monoaminergic sensitization induced by TNF alpha and the relationship of this to acquisition of the avoidance response. (c) 2006 Elsevier B.V. All rights reserved. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Brennan, FX (reprint author), Philadelphia VA Med Ctr, Med Res 151,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Brennan_f@mail.trc.upenn.edu NR 17 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 13 PY 2006 VL 1109 BP 142 EP 145 DI 10.1016/j.brainres.2006.06.040 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 086ZP UT WOS:000240712100016 PM 16836982 ER PT J AU Huddleston, J Alaiti, A Goldvasser, D Scarborough, D Freiberg, A Rubash, H Malchau, H Harris, W Krebs, D AF Huddleston, James Alaiti, Amer Goldvasser, Dov Scarborough, Donna Freiberg, Andrew Rubash, Harry Malchau, Henrik Harris, William Krebs, David TI Ambulatory measurement of knee motion and physical activity: preliminary evaluation of a smart activity monitor SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article ID TRIAXIAL ACCELEROMETER; ENERGY-EXPENDITURE; WALKING ACTIVITY; VALIDATION; PEDOMETER; QUESTIONNAIRE; POPULATION; ACTOMETER; VALIDITY; SYSTEM AB Background: There is currently a paucity of devices available for continuous, long-term monitoring of human joint motion. Non-invasive, inexpensive devices capable of recording human activity and joint motion have many applications for medical research. Such a device could be used to quantify range of motion outside the gait laboratory. The purpose of this study was to test the accuracy of the modified Intelligent Device for Energy Expenditure and Activity (IDEEA) in measuring knee flexion angles, to detect different physical activities, and to quantify how often healthy subjects use deep knee flexion in the ambulatory setting. Methods: We compared Biomotion Laboratory (BML) "gold standard" data to simultaneous IDEEA measures of knee motion and gait, step up/down, and stair descent in 5 healthy subjects. In addition, we used a series of choreographed physical activities outside the BML to confirm the IDEEA's ability to accurately measure 7 commonly-performed physical activities. Subjects then continued data collection during ordinary activities outside the gait laboratory. Results: Pooled correlations between the BML and IDEEA knee flexion angles were .97 +/- .03 for step up/down, .98 +/- .02 for stair descent, and .98 +/- .01 for gait. In the BML protocol, the IDEEA accurately identified gait, but was less accurate in identifying step up/down and stair descent. During sampling outside the BML, the IDEEA accurately detected walking, running, stair ascent, stair descent, standing, lying, and sitting. On average, subjects flexed their knees > 120 degrees for 0.17% of their data collection periods outside the BML. Conclusion: The modified IDEEA system is a useful clinical tool for evaluating knee motion and multiple physical activities in the ambulatory setting. These five healthy subjects rarely flexed their knees > 120 degrees. C1 Harvard Univ, Sch Med, Harris Orthopaed Biomech & Biomat Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomot Lab,MGH Inst Hlth, Boston, MA 02129 USA. Stanford Univ, Sch Med, Dept Orthopaed Surg, Stanford, CA 94305 USA. RP Huddleston, J (reprint author), Harvard Univ, Sch Med, Harris Orthopaed Biomech & Biomat Lab, Massachusetts Gen Hosp, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM jhuddleston@stanford.edu; alaiti@partners.org; dgoldvasser@partners.org; dscarborough@partners.org; afreiberg@partners.org; hrubash@partners.org; hmalchau@partners.org; wharris.obbl@partners.org; dkrebs@partners.org NR 25 TC 4 Z9 4 U1 3 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD SEP 13 PY 2006 VL 3 PG 10 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 235UA UT WOS:000251258600001 ER PT J AU Gvilia, I Xu, F McGinty, D Szymusiak, R AF Gvilia, Irma Xu, Feng McGinty, Dennis Szymusiak, Ronald TI Homeostatic regulation of sleep: A role for preoptic area neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sleep deprivation; non-REM sleep; ventrolateral preoptic area; median preoptic nucleus; GABA; sleep diurnality ID WAKING DISCHARGE PATTERNS; FOS PROTEIN EXPRESSION; EYE-MOVEMENT SLEEP; C-FOS; OREXIN NEURONS; GALANINERGIC NEURONS; GABAERGIC NEURONS; NUCLEUS NEURONS; BASAL FOREBRAIN; HYPOTHALAMUS AB The median preoptic nucleus (MnPN) and the ventrolateral preoptic area (vlPOA) contain putative sleep-regulatory neurons that exhibit elevated discharge rates during sleep compared with waking. Expression of c-Fos protein immunoreactivity (IR) in GABAergic neurons in the MnPN and the vlPOA is high in spontaneously sleeping rats and in rats undergoing recovery sleep after sleep deprivation. However, it is unclear whether c-Fos-IR in these neurons is evoked by increases in sleep pressure or by increases in sleep amount. We examined c-Fos-IR in MnPN and vlPOA neurons under experimental conditions that dissociated homeostatic sleep pressure, sleep amount, and time of day. Groups of rats with strong diurnal rhythms in sleep-wake organization were killed after (1) spontaneous sleep in the light, (2) spontaneous sleep in the dark, (3) sleep deprivation (SLD) in the light and (4) recovery sleep after SLD in the light. Numbers of GABAergic neurons expressing c-Fos-IR in the MnPN were significantly higher after SLD in the light compared with spontaneous sleep and recovery sleep in the light. In contrast, Fos-IR in vlPOA GABAergic neurons was most prevalent after spontaneous sleep and recovery sleep in the light. No light-dark differences in Fos-IR were observed in the MnPN after SLD in groups of rats with weak or absent diurnal sleep-waking rhythms. Our findings define potential roles for MnPN and vlPOA GABAergic neurons in homeostatic aspects of sleep regulation. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. I Beritashvili Inst Physiol, Tbilisi, Rep of Georgia. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Gvilia, I (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, 151A3,16111 Plummer St, North Hills, CA 91343 USA. EM irmagvilia@hotmail.com; rszym@ucla.edu FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH63323] NR 28 TC 61 Z9 63 U1 3 U2 11 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 SEP 13 PY 2006 VL 26 IS 37 BP 9426 EP 9433 DI 10.1523/JNEUROSCI.2012-06.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 083YM UT WOS:000240495500010 PM 16971526 ER PT J AU Pham, W Pantazopoulos, P Moore, A AF Pham, Wellington Pantazopoulos, Pamela Moore, Anna TI Imaging farnesyl protein transferase using a topologically activated probe SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID FARNESYLTRANSFERASE; INHIBITORS; CANCER; CELLS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Vanderbilt Univ, Inst Imaging Sci, 1161 21st Ave S, Nashville, TN 37232 USA. EM amoore@helix.mgh.harvard.edu NR 11 TC 5 Z9 5 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 13 PY 2006 VL 128 IS 36 BP 11736 EP 11737 AR JA063599X DI 10.1021/ja063599x PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 081BJ UT WOS:000240291900004 PM 16953595 ER PT J AU Schon, A Madani, N Klein, JC Hubicki, A Ng, D Yang, X Smith, AB Sodroski, J Freire, E AF Schon, Arne Madani, Navid Klein, Jeffrey C. Hubicki, Amy Ng, Danny Yang, Xinzhen Smith, Amos B., III Sodroski, Joseph Freire, Ernesto TI Thermodynamics of binding of a low-molecular-weight CD4 mimetic to HIV-1 gp120 SO BIOCHEMISTRY LA English DT Article ID ENVELOPE GLYCOPROTEINS; CONFORMATIONAL-CHANGES; RECEPTOR-BINDING; VIRUS; ENTRY; MINIPROTEIN; INHIBITOR; SITE; NEUTRALIZATION; EPITOPES AB NBD-556 and the chemically and structurally similar NBD-557 are two low-molecular weight compounds that reportedly block the interaction between the HIV-1 envelope glycoprotein gp120 and its receptor, CD4. NBD-556 binds to gp120 with a binding affinity of 2.7 x 10(5) M-1 ( K-d = 3.7 mu M) in a process characterized by a large favorable change in enthalpy partially compensated by a large unfavorable entropy change, a thermodynamic signature similar to that observed for binding of sCD4 to gp120. NBD556 binding is associated with a large structuring of the gp120 molecule, as also demonstrated by CD spectroscopy. NBD-556, like CD4, activates the binding of gp120 to the HIV-1 coreceptor, CCR5, and to the 17b monoclonal antibody, which recognizes the coreceptor binding site of gp120. NBD-556 stimulates HIV-1 infection of CD4-negative, CCR5-expressing cells. The thermodynamic signature of the binding of NBD- 556 to gp120 is very different from that of another viral entry inhibitor, BMS-378806. Whereas NBD- 556 binds gp120 with a large favorable enthalpy and compensating unfavorable entropy changes, BMS-378806 does so with a small binding enthalpy change in a mostly entropy-driven process. NBD556 is a competitive inhibitor of sCD4 and elicits a similar structuring of the coreceptor binding site, whereas BMS-378806 does not compete with sCD4 and does not induce coreceptor binding. These studies demonstrate that low-molecular-weight compounds can induce conformational changes in the HIV-1 gp120 glycoprotein similar to those observed upon CD4 binding, revealing distinct strategies for inhibiting the function of the HIV-1 gp120 envelope glycoprotein. Furthermore, competitive and noncompetitive compounds have characteristic thermodynamic signatures that can be used to guide the design of more potent and effective viral entry inhibitors. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. RP Freire, E (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. EM ef@jhu.edu FU NIAID NIH HHS [R37 AI024755, AI24755, AI41851, R01 AI041851, R01 AI041851-10, R37 AI024755-22]; NIGMS NIH HHS [F32 GM072111, GM56550, P01 GM056550, P01 GM056550-120010, R01 GM057144, R01 GM057144-11]; NINDS NIH HHS [F32 NS043260, F32 NS43260 M] NR 27 TC 96 Z9 101 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 12 PY 2006 VL 45 IS 36 BP 10973 EP 10980 DI 10.1021/bi061193r PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080MG UT WOS:000240251300020 PM 16953583 ER PT J AU Bruce, BB AF Bruce, Beau B. TI Neuro-ophthalmology Internet digital media library SO NEUROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bruce, BB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, WACC 835,55 Fruit St, Boston, MA 02114 USA. EM bbruce@partners.org 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 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 12 PY 2006 VL 67 IS 5 BP E10 EP E10 DI 10.1212/01.wnl.0000233994.65758.c9 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 083EC UT WOS:000240437700058 PM 16966529 ER PT J AU Fitch, KV Anderson, EJ Hubbard, JL Carpenter, SJ Waddell, WR Caliendo, AM Grinspoon, SK AF Fitch, Kathleen V. Anderson, Ellen J. Hubbard, Jane L. Carpenter, Sara J. Waddell, William R. Caliendo, Angela M. Grinspoon, Steven K. TI Effects of a lifestyle modification program in HIV-infected patients with the metabolic syndrome SO AIDS LA English DT Article DE blood pressure; cardiovascular risk; HIV; lifestyle modification; metabolic syndrome ID HUMAN-IMMUNODEFICIENCY-VIRUS; CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; RISK-FACTORS; LIPODYSTROPHY; ABNORMALITIES; INTERVENTION; PREVALENCE AB Objectives: A large percentage of HIV-infected patients receiving HAART develop the metabolic syndrome. In this study, we sought to determine whether lifestyle modification improves metabolic syndrome criteria, including waist circumference, blood pressure, fasting blood sugar, triglycerides, and HDL-cholesterol among HIV-infected patients with the metabolic syndrome. Design: We conducted a randomized, 6-month study in HIV-infected patients with metabolic syndrome as defined by the National Cholesterol Education Program. Subjects were randomly assigned to an intensive lifestyle modification program, which included weekly one-on-one counseling sessions with a registered dietician, or observation (control group). Methods: Metabolic syndrome criteria and cardiovascular parameters, including blood pressure, body composition, submaximal stress testing, lipids and other biochemical parameters were determined. Results: Thirty-four patients were randomly assigned and 28 subjects completed the study. Compared with the control group, subjects randomly assigned to the lifestyle modification program demonstrated significant decreases in waist circumference (-2.6 +/- 1.1 versus 1.2 +/- 1.0 cm, P = 0.022), systolic blood pressure (-13 +/- 4 versus 4 +/- 4 mmHg, P = 0.008), hemaglobin A1C (-0.1 +/- 0.1 versus 0.2 +/- 0.1 %, P = 0.017), lipodystrophy score (-1.2 +/- 0.3 versus 0.9 +/- 0.6, P = 0.006) and increased activity (17.7 +/- 14.3 versus -33.1 +/- 12.7 metabolic equivalents, P=0.014) as measured by the Modifiable Activity Questionnaire, but lipid levels did not improve. Conclusion: These data demonstrate that intensive lifestyle modification significantly improved important cardiovascular risk indices in HIV-infected patients with the metabolic syndrome. Lifestyle modification may be a useful strategy to decrease cardiovascular risk in this population. (c) 2006 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Phys Therapy Dept, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutrit Metab, Longfellow 207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11, R01 DK-49302] NR 33 TC 57 Z9 58 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 11 PY 2006 VL 20 IS 14 BP 1843 EP 1850 DI 10.1097/01.aids.0000244203.95758.db PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 092BK UT WOS:000241071800007 PM 16954725 ER PT J AU Osipova, D Rantanen, K Ahveninen, J Ylikoski, R Happola, O Strandberg, T Pekkonen, E AF Osipova, Daria Rantanen, Kirsi Ahveninen, Jyrki Ylikoski, Raija Happola, Olli Strandberg, Tirno Pekkonen, Eero TI Source estimation of spontaneous MEG oscillations in mild cognitive impairment SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; EEG; memory; alpha rhythm; aging; magnetoencephalography; mild cognitive impairment ID ALZHEIMERS-DISEASE; MAGNETOENCEPHALOGRAPHIC DATA; EEG SYNCHRONIZATION; THETA; GENERATION; COHERENCE; TASK AB Mild cognitive impairment (MCI) is a memory disorder often preceding Alzheimer's disease (AD). AD has been shown to be associated with abnormal generation of spontaneous electromagnetic activity. We investigated whether the cortical generation of spontaneous brain oscillations in MCI shows changes resembling those observed in AD. A minimum current estimates algorithm was applied to identify cortical sources of magnetoencephalographic (MEG) spontaneous brain oscillations in male MCI patients with a clear memory disorder and in healthy elderly controls. This data was subsequently compared to a male subsample of AD patients from an earlier study. While there were clear oscillatory abnormalities in AD patients, there was no evidence of significant changes in the alpha source distribution in MCI patients as compared to healthy controls. Deficits in the distribution of oscillatory sources in the resting state are thus likely to occur at later stages of cognitive impairment than MCI. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Engn Ctr, FIN-00014 Helsinki, Finland. Helsinki Brain Res Ctr, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. Oulu Univ, Dept Publ Hlth Sci & Gen Practice, SF-90220 Oulu, Finland. Univ Hosp, SF-90220 Oulu, Finland. RP Osipova, D (reprint author), Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, POB 9, FIN-00014 Helsinki, Finland. EM daria.osipova@helsinki.fi OI Pekkonen, Eero/0000-0003-1621-8752 FU NICHD NIH HHS [R01 HD040712] NR 28 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 11 PY 2006 VL 405 IS 1-2 BP 57 EP 61 DI 10.1016/j.neulet.2006.06.045 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 079IO UT WOS:000240169500012 PM 16854528 ER PT J AU Suzuki, T Delgado-Escueta, AV Alonso, ME Morita, R Okamura, N Sugimoto, Y Bai, DS Medina, MT Bailey, JN Rasmussen, A Ramos-Peek, J Cordova, S Rubio-Donnadieu, F Ochoa, A Jara-Prado, A Inazawa, J Yamakawa, K AF Suzuki, Toshimitsu Delgado-Escueta, Antonio V. Alonso, Maria E. Morita, Ryoji Okamura, Nami Sugimoto, Yoshihisa Bai, Dongsheng Medina, Marco T. Bailey, Julia N. Rasmussen, Astrid Ramos-Peek, Jaime Cordova, Sergio Rubio-Donnadieu, Francisco Ochoa, Adriana Jara-Prado, Aurelio Inazawa, Johji Yamakawa, Kazuhiro TI Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy SO NEUROSCIENCE LETTERS LA English DT Article DE juvenile myoclonic epilepsy; Myoclonin1/EFHCI1; EJM1; 6p11-p12 ID IDIOPATHIC GENERALIZED EPILEPSY; CHILDHOOD ABSENCE EPILEPSY; CHROMOSOME 6P12; GENOME BROWSER; LINKAGE; LOCUS; CANDIDATE; IDENTIFICATION; HETEROGENEITY; GENETICS AB Juvenile myoclonic epilepsy (JME) is a distinct form of idiopathic generalized epilepsy (IGE). One of the candidate regions for human JME has been mapped on chromosome band 6p11-p12 by linkage analyses and is termed EJM1 (MIM 254770). Recently, we reported the reduction of the EJM1 region to 3.5cM that contains 18 genes, the exclusion of three genes (LRRC1, GCLC, KIAA0057) by mutation analyses, and the identification of Myoclonin1/EFHC1 as the EJM1 gene. Here, we describe detailed physical and transcriptome maps of the 3.5cM EJM1 region, and detailed results of mutation analyses for the remained 14 genes (HELO1, GCMA, KIAA0936, FBX09, GSTA3, GSTA4, PTD011, KIAA0576, LMPB1, ILI7F, MCM3, PKHD1, KIAA0105, TFAP2B) in patients with JME. We identified 49 single nucleotide changes in eight genes. Twelve amino acid substitutions occurred in two genes, I I silent mutations in seven genes, and 26 in the non-coding or intronic regions of seven genes. Twelve amino acid substitutions in the two genes (ILI7F, PKHD1) were also observed in healthy control individuals or did not co-segregate with the disease phenotypes in other family members. Thus, the absence of significant and potentially functional mutations in the remaining 14 genes further supports the concept that Myoclonin1/EFHC1 is the EJM1 gene in chromosome 6p12. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 RIKEN, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Univ Calif Los Angeles, Geffen Sch Med, Comprehens Epilepsy Program, Epilepsy Genet Genom Labs, Los Angeles, CA 90073 USA. VA GLAHS W Los Angeles, Los Angeles, CA 90073 USA. Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. Natl Autonomous Univ, Tegucigalpa, Honduras. Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA. Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Cytogenet, Tokyo, Japan. RP Delgado-Escueta, AV (reprint author), W Los Angeles DVA Med Ctr, Room 3405 127B,Bldg 500,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM escueta@ucla.edu; yamakawa@brain.riken.jp RI Yamakawa, Kazuhiro/N-5050-2015 FU NINDS NIH HHS [NS42376] NR 33 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 11 PY 2006 VL 405 IS 1-2 BP 126 EP 131 DI 10.1016/j.neulet.2006.06.038 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 079IO UT WOS:000240169500025 PM 16876319 ER PT J AU Kotton, CN Lankowski, AJ Scott, N Sisul, D Chen, LM Raschke, K Borders, G Boaz, M Spentzou, A Galan, JE Hohmann, EL AF Kotton, Camille N. Lankowski, Alexander J. Scott, Nathaniel Sisul, David Chen, Li Mei Raschke, Katherine Borders, Genevieve Boaz, Mark Spentzou, Aggeliki Galan, Jorge E. Hohmann, Elizabeth L. TI Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system SO VACCINE LA English DT Article DE Salmonella; vaccine; HIV; mucosal; immunity ID HELICOBACTER-PYLORI UREASE; T-CELL RESPONSES; ADULT VOLUNTEERS; VACCINE DEVELOPMENT; BACTERIAL SURVIVAL; HEALTHY-VOLUNTEERS; ESCHERICHIA-COLI; IMMUNE-RESPONSE; HOST-RESISTANCE; LIVE VACCINES AB Background: CKS257 (Sabnonella typhimurium SL1344 Delta phoP/phoQ Delta aroA Delta asd Delta strA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag. Methods: HIV Gag was expressed as a fusion protein of a Salmonella Type III secretion system protein SopE, from a balanced lethal asd-based plasmid. Eighteen healthy adults were given single escalating oral doses of 5 x 10(6) to 1 x 10(10) CFU of CKS257 and were monitored for clinical events, shedding and immune responses. Results: Adverse events were mild except at the highest dose. Volunteers shed the organism an average of 5.1 days (range 0-13 days). Eighty-three percent (15/18) of subjects had a mucosal immune response to Salmonella LPS and flagella by IgA ELISPOT assay. Seventy-two percent (13/18) of subjects seroconverted to Salmonella antigens. No volunteer had a response to recombinant Gag as measured by serology, IgA ELISPOT, or immediate ex vivo gamma-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving >= 5 x 10(8) CFU had a response to HIV peptides in a cultured gamma-interferon ELISPOT assay. Conclusions: Although immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02114 USA. Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA. Int AIDS Vaccine Initiat, Sect Microbial Pathogenesis, Ctr Mol Med, New York, NY USA. IAVI Core Lab, London, England. RP Hohmann, EL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM ehohmann@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIAID NIH HHS [K08 AI001701, AI-067077, R01 AI067103, R01 AI46963]; PHS HHS [R01 51206] NR 55 TC 44 Z9 48 U1 0 U2 4 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 SEP 11 PY 2006 VL 24 IS 37-39 BP 6216 EP 6224 DI 10.1016/j.vaccine.2006.05.094 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 086VX UT WOS:000240702200006 PM 16824652 ER PT J AU Jiang, SS Song, RJ Popov, S Mirshahidi, S Ruprecht, RM AF Jiang, Shisong Song, Ruijiang Popov, Sergei Mirshahidi, Saied Ruprecht, Ruth M. TI Overlapping synthetic peptides as vaccines SO VACCINE LA English DT Article DE overlapping synthetic peptides; cell-mediated immunity; vaccine ID CYTOTOXIC T-LYMPHOCYTES; IMMUNODEFICIENCY-VIRUS TYPE-1; DENDRITIC CELL VACCINE; CLASS-I MOLECULES; CTL EPITOPE; METASTATIC MELANOMA; EFFECTIVE INDUCTION; CROSS-PRESENTATION; HIV VACCINES; DNA AB Several vaccine strategies aim to generate cell-mediated immunity (CMI) against microorganisms or tumors. While epitope-based vaccines offer advantages, knowledge of specific epitopes and frequency of major histocompatibility complex (MHC) alleles is required. Here we show that using promiscuous overlapping synthetic peptides (OSP) as immunogens generated peptide-specific CMI in all vaccinated outbred mice and in different strains of inbred mice; CMI responses also recognized viral proteins. OSP immunogens also induced CMI ex vivo in dendritic cell/T-cell cocultures involving cells from individuals with different HLA haplotypes. Thus, broad CMI was induced by OSP in different experimental settings, using different immunogens, without identifying either epitopes or MHC backgrounds of the vaccinees. (c) 2006 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu FU NCIRD CDC HHS [IP30 28691]; NIAID NIH HHS [R01 AI43839, P01 AI48240] NR 57 TC 7 Z9 7 U1 0 U2 2 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 SEP 11 PY 2006 VL 24 IS 37-39 BP 6356 EP 6365 DI 10.1016/j.vaccine.2006.04.070 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 086VX UT WOS:000240702200023 PM 16793181 ER PT J AU Bearss, DJ Grand, CL Vankayalapati, H MacRae, C AF Bearss, David J. Grand, Cory L. Vankayalapati, Hariprasad MacRae, Calum TI Identification of novel PKC inhibitors using a computationally-driven screening system SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bearss, David J.; Grand, Cory L.; Vankayalapati, Hariprasad] SuperGen Inc, Salt Lake City, UT 84109 USA. [MacRae, Calum] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP 10 PY 2006 VL 232 MA 150-COMP BP 33 EP 33 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781604030 ER PT J AU Wagner, BK Tseng, YH Kim, YK Kahn, CR Schreiber, SL AF Wagner, Bridget K. Tseng, Yu-Hua Kim, Young-kwon Kahn, C. Ronald Schreiber, Stuart L. TI High-throughput screening: A chemical-genomic investigation of adipogenesis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wagner, Bridget K.; Kim, Young-kwon] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA 02142 USA. [Tseng, Yu-Hua; Kahn, C. Ronald] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Schreiber, Stuart L.] Broad Inst Harvard & MIT, Dept Chem & Chem Biol, Howard Hughes Med Inst, Cambridge, MA 02142 USA. 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 SEP 10 PY 2006 VL 232 MA 121-BIOL BP 792 EP 792 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600695 ER PT J AU Jia, XQ Yeo, Y Clifton, RJ Jiao, T Kohane, DS Kobler, J Zeitels, SM Langer, R AF Jia, Xinqiao Yeo, Yoon Clifton, Rodney J. Jiao, Tong Kohane, Daniel S. Kobler, James Zeitels, Steven M. Langer, Robert TI POLY 277-Hyaluronic acid-based microgels for vocal fold regeneration SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Jia, Xinqiao] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA. [Yeo, Yoon; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Clifton, Rodney J.; Jiao, Tong] Brown Univ, Div Engn, Providence, RI 02912 USA. [Kohane, Daniel S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. [Kobler, James; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 SEP 10 PY 2006 VL 232 MA 277-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DC UT WOS:000207781701584 ER PT J AU Verdine, GL AF Verdine, Gregory L. TI ORGN 247-Converting peptides to drugs 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, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP 10 PY 2006 VL 232 MA 247-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781608755 ER PT J AU Wang, SH King, KR Jayaraman, A Toner, M Yarmush, ML AF Wang, Sihong King, Kevin R. Jayaraman, Arul Toner, Mehmet Yarmush, Martin L. TI BIOT 213-Real time profiling of gene expression dynamics using a microfluidic living cell array SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Engn Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP 10 PY 2006 VL 232 MA 213-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601461 ER PT J AU Yuan, JY Degterev, A Huang, ZH Boyce, M Jagtap, P Cuny, G Moskowitz, M AF Yuan, Junying Degterev, Alexei Huang, Zhihong Boyce, Mike Jagtap, Prakash Cuny, Greg Moskowitz, Michael TI MEDI 19-Studying mechanisms of cell death: From apoptosis to necrosis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Yuan, Junying; Degterev, Alexei; Boyce, Mike] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Jagtap, Prakash; Cuny, Greg] Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Cambridge, MA 02139 USA. [Jagtap, Prakash; Cuny, Greg] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Huang, Zhihong; Moskowitz, Michael] Massachusetts Gen Hosp, Stroke & Neuromascular Regulat Lab, Boston, MA 02114 USA. 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 SEP 10 PY 2006 VL 232 MA 19-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607588 ER PT J AU Zhu, HJ Sekine, K Toner, M Macal, M Dandekar, S Revzin, A AF Zhu, He James Sekine, Kazuhiko Toner, Mehmet Macal, Monica Dandekar, Satya Revzin, Alexander TI BIOT 216-Antibody microarrays for capture and characterization of leukocytes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhu, He James; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Sekine, Kazuhiko; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA 02129 USA. [Macal, Monica; Dandekar, Satya] Univ Calif Davis, Dept Immunol & Microbiol, Sch Med, Davis, CA 95616 USA. RI Sekine, Kazuhiko/I-5835-2012 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 SEP 10 PY 2006 VL 232 MA 216-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601734 ER PT J AU Steyerberg, EW Neville, BA Koppert, LB Lemmens, VEPP Tilanus, HW Coebergh, JWW Weeks, JC Earle, CC AF Steyerberg, Ewout W. Neville, Bridget A. Koppert, Linctta B. Lemmens, Valery E. P. P. Tilanus, Hugo W. Coebergh, Jan-Willem W. Weeks, Jane C. Earle, Craig C. TI Surgical mortality in patients with Esophageal cancer: Development and validation of a simple risk score SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SEER-MEDICARE DATA; RANDOMIZED CONTROLLED-TRIALS; HOSPITAL VOLUME; OPERATIVE MORTALITY; CLAIMS DATA; GASTROESOPHAGEAL JUNCTION; COMORBIDITY INDEX; UNITED-STATES; CO-MORBIDITY; SURGERY AB Purpose Surgery has curative potential in a proportion of patients with esophageal cancer, but is associated with considerable perioperative risks. We aimed to develop and validate a simple risk score for surgical mortality that could be applied to administrative data, Patients and Methods We analyzed 3,592 esophagectomy patients from four cohorts. We applied logistic regression analysis to predict mortality occurring within 30 days after esophagectomy for 1,327 esophageal cancer patients older than 65 years of age, diagnosed between 1991 and 1996 in the linked Surveillance, Epidemiology and End Results (SEER) - Medicare database. A simple score chart for preoperative risk assessment of surgical mortality was developed and validated on three other cohorts, including 714 SEER-Medicare patients diagnosed between 1997 and 1999, 349 patients from a population-based registry in the Netherlands diagnosed between 1993 and 2001, and 1,202 patients from a referral hospital in the Netherlands diagnosed between 1980 and 2002. Results Surgical mortality in the four cohorts was 11% (147 of 1,327), 10% (74 of 714), 7% (25 of 349), and 4% (45 of 1,202), respectively. Predictive patient characteristics included age, comorbidity (cardiac, pulmonary, renal, hepatic, and diabetes), preoperative radiotherapy or combined chemoradiotherapy, and a relatively low hospital volume. At validation, the simple score showed good agreement of predicted risks with observed mortality rates (calibration), but low discrimination (area under the receiver operating characteristic curve 0.58 to 0.66). Conclusion A simple risk score combining clinical characteristics along with hospital volume to predict surgical mortality after esophagectomy from administrative data may form a basis for risk adjustment in quality of care assessment. C1 Univ Med Ctr Rotterdam, Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. Univ Med Ctr Rotterdam, Erasmus MC, Dept Surg, NL-3000 CA Rotterdam, Netherlands. Eindhoven Canc Registry, Comprehens Canc Ctr S, Eindhoven, Netherlands. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Steyerberg, EW (reprint author), Univ Med Ctr Rotterdam, Erasmus MC, Dept Publ Hlth, AE-236,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM e.steyerberg@erasmusmc.nl OI Steyerberg, Ewout/0000-0002-7787-0122 NR 51 TC 108 Z9 112 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2006 VL 24 IS 26 BP 4277 EP 4284 DI 10.1200/JCO.2005.05.0658 PG 8 WC Oncology SC Oncology GA 086AK UT WOS:000240645300008 PM 16963730 ER PT J AU Gordon, MS Matei, D Aghajanian, C Matulonis, UA Brewer, M Fleming, GF Hainsworth, JD Garcia, AA Pegram, MD Schilder, RJ Cohn, DE Roman, L Derynck, MK Ng, K Lyons, B Allison, DE Eberhard, DA Pham, TQ Dere, RC Karlan, BY AF Gordon, Michael S. Matei, Daniela Aghajanian, Carol Matulonis, Ursula A. Brewer, Molly Fleming, Gini F. Hainsworth, John D. Garcia, Agustin A. Pegram, Mark D. Schilder, Russell J. Cohn, David E. Roman, Lynda Derynck, Mika K. Ng, Kimmie Lyons, Benjamin Allison, David E. Eberhard, David A. Pham, Thinh Q. Dere, Randall C. Karlan, Beth Y. TI Clinical activity of Pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: Potential predictive relationship with tumor HER2 activation status SO JOURNAL OF CLINICAL ONCOLOGY 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 METASTATIC COLORECTAL-CANCER; EPIDERMAL-GROWTH-FACTOR; PHASE-II TRIAL; FACTOR RECEPTOR; ERBB RECEPTORS; ONCOLOGY-GROUP; BREAST-CANCER; BEVACIZUMAB; CAPECITABINE; EXPRESSION AB Purpose Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC. Patients and Methods Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort I to assay for phosphorylated HER2 (pHER2). Results Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3%; 95% Cl, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50% (includes two partial responses and four patients with SD >= 6 months; total clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2(n = 20; P =.14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50% (one confirmed by central facility). Conclusion Pertuzumab is well tolerated with a RR of 4.3% in heavily-pretreated OC patients. Further studies on pHEB2 as a diagnostic are warranted. C1 Cedars Sinai Med Ctr, Womens Canc Res Inst, Los Angeles, CA 90048 USA. Arizona Canc Ctr, Tucson, AZ USA. Arizona Canc Ctr, Scottsdale, AZ USA. Indiana Univ, Indianapolis, IN 46204 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Harvard Canc Inst, Boston, MA USA. Univ Chicago, Chicago, IL 60637 USA. Sarah Cannon Res Inst, Nashville, TN USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Genentech Inc, San Francisco, CA 94080 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. RP Karlan, BY (reprint author), Cedars Sinai Med Ctr, Womens Canc Res Inst, 8700 Beverly Blvd,290W, Los Angeles, CA 90048 USA. EM Beth.Karlan@cshs.org NR 38 TC 147 Z9 157 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2006 VL 24 IS 26 BP 4324 EP 4332 DI 10.1200/JCO.2005.05.4221 PG 9 WC Oncology SC Oncology GA 086AK UT WOS:000240645300014 PM 16896006 ER PT J AU Poulin, DL DeCaprio, JA AF Poulin, Danielle L. DeCaprio, James A. TI Is there a role for SV40 in human cancer? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID LARGE-T-ANTIGEN; HUMAN-BRAIN-TUMORS; VACUOLATING VIRUS SV40; NON-HODGKINS-LYMPHOMA; HUMAN PLEURAL MESOTHELIOMA; POLYMERASE-CHAIN-REACTION; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; POLYOMAVIRUS TYPE BK; SIMIAN VIRUS-40; DNA-SEQUENCES AB The question of whether Simian Virus 40 (SV40) can cause human tumors has been one of the most highly controversial topics in cancer research during the last 50 years. The longstanding debate began with the discovery of SV40 as a contaminant in poliovirus vaccine stocks that were used to inoculate approximately 100 million children and adults in the United States between 1955 and 1963, and countless more throughout the world. Concerns regarding the potential health risk of SV40 exposure were reinforced by studies demonstrating SV40's potential to transform human cells and promote tumor growth in animal models. Many studies have attempted to assess the relationship between the potential exposure of humans to SV40 and cancer incidence. Reports of the detection of SV40 DNA in a variety of cancers have raised serious concerns as to whether the inadvertent inoculation with SV40 has led to the development of cancer in humans. However, inconsistent reports linking SV40 with various tumor types has led to conflicting views regarding the potential of SV40 as a human cancer virus. Several recent studies suggest that older detection methodologies were flawed, and the limitations of these methods could account for most, if not all, of the positive correlations of SV40 in human tumors to date. Although many people may have been exposed to SV40 by polio vaccination, there is inadequate evidence to support widespread SV40 infection in the population, increased tumor incidence in those individuals who received contaminated vaccine, or a direct role for SV40 in human cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Mayer 457,44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu NR 119 TC 78 Z9 82 U1 0 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2006 VL 24 IS 26 BP 4356 EP 4365 DI 10.1200/JCO.2005.03.7101 PG 10 WC Oncology SC Oncology GA 086AK UT WOS:000240645300018 PM 16963733 ER PT J AU Patel, DN Bailey, SR Gresham, JK Schuchman, DB Shelhamer, JH Goldstein, BJ Foxwell, BM Stemerman, MB Maranchie, JK Valente, AJ Mummidi, S Chandrasekar, B AF Patel, Devang N. Bailey, Steven R. Gresham, John K. Schuchman, David B. Shelhamer, James H. Goldstein, Barry J. Foxwell, Brian M. Stemerman, Michael B. Maranchie, Jodi K. Valente, Anthony J. Mummidi, Srinivas Chandrasekar, Bysam TI TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE atherosclerosis; coronary disease; endotoxins; signal transduction; MAP kinase ID N-TERMINAL KINASE; SCAVENGER RECEPTOR; KAPPA-B; OXIDIZED LIPOPROTEIN; ENDOTHELIAL-CELLS; CHEMOKINE CXCL16; INTERFERON-GAMMA; CUTTING EDGE; ACTIVATION; LIGAND AB CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappa B (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis. (c) 2006 Elsevier Inc. All rights reserved. C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. Univ London Imperial Coll Sci Technol & Med, London, England. Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. Univ Massachusetts, Dept Surg, Worcester, MA 01605 USA. Univ Massachusetts, Dept Cell Biol, Worcester, MA 01605 USA. RP Chandrasekar, B (reprint author), S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. EM chandraseka@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008; OI Mummidi, Srinivas/0000-0002-4068-6380; Maranchie, Jodi/0000-0002-8534-9468 FU NHLBI NIH HHS [HL68020] NR 35 TC 38 Z9 41 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 8 PY 2006 VL 347 IS 4 BP 1113 EP 1120 DI 10.1016/j.bbre.2006.07.015 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 072NW UT WOS:000239681100038 PM 16870145 ER PT J AU Haigis, MC Mostoslavsky, R Haigis, KM Fahie, K Christodoulou, DC Murphy, AJ Valenzuela, DM Yancopoulos, GD Karow, M Blander, G Wolberger, C Prolla, TA Weindruch, R Alt, FW Guarente, L AF Haigis, Marcia C. Mostoslavsky, Raul Haigis, Kevin M. Fahie, Kamau Christodoulou, Danos C. Murphy, Andrew J. Valenzuela, David M. Yancopoulos, George D. Karow, Margaret Blander, Gil Wolberger, Cynthia Prolla, Tomas A. Weindruch, Richard Alt, Frederick W. Guarente, Leonard TI SIRT4 inhibits glutamate dehydrogehase and opposes the effects of calorie restriction in pancreatic beta cells SO CELL LA English DT Article ID STIMULATED INSULIN-SECRETION; LIFE-SPAN EXTENSION; ADP-RIBOSYLATION; SACCHAROMYCES-CEREVISIAE; DEPENDENT DEACETYLASE; TRANSCRIPTION FACTORS; PROTEIN DEACETYLASES; ENZYME-ACTIVITIES; MAMMALIAN SIR2; MOUSE-LIVER AB Sir2 is an NAD-dependent deacetylase that connects metabolism with longevity in yeast, flies, and worms. Mammals have seven Sir2 homologs (SIRT1-7). We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity. GDH is known to promote the metabolism of glutamate and glutamine, generating ATP, which promotes insulin secretion. Loss of SIRT4 in insulinoma cells activates GDH, thereby upregulating amino acid-stimulated insulin secretion. A similar effect is observed in pancreatic beta cells from mice deficient in SIRT4 or on the dietary regimen of calorie restriction (CR). Furthermore, GDH from SIRT4-deficient or CR mice is insensitive to phosphodiesterase, an enzyme that cleaves ADP-ribose, suggesting the absence of ADP-ribosylation. These results indicate that SIRT4 functions in beta cell mitochondria to repress the activity of GDH by ADP-ribosylation, thereby downregulating insulin secretion in response to amino acids, effects that are alleviated during CR. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, CBR Inst Biomed Res, Howard Hughes Med Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Vet Adm Hosp, Madison, WI 53705 USA. Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. RP Guarente, L (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM leng@mit.edu NR 55 TC 533 Z9 562 U1 3 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 8 PY 2006 VL 126 IS 5 BP 941 EP 954 DI 10.1016/j.cell.2006.06.057 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 086LO UT WOS:000240675000021 PM 16959573 ER PT J AU Franco, S Alt, FW Manis, JP AF Franco, Sonia Alt, Frederick W. Manis, John P. TI Pathways that suppress programmed DNA breaks from progressing to chromosomal breaks and translocations SO DNA REPAIR LA English DT Review DE DNA damage response; class switch recombination; lymphoma ID CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; ATM-DEFICIENT MICE; INDUCED CYTIDINE DEAMINASE; DEPENDENT PROTEIN-KINASE; HISTONE H2AX PHOSPHORYLATION; DAMAGE-RESPONSE PATHWAYS; END-JOINING PATHWAY; V(D)J RECOMBINATION; GENOMIC INSTABILITY AB Guarding the genome against internal and external assaults requires the coordinated interaction of multiple cellular networks to sense, respond to, and repair breaks in chromosomal DNA. Both external factors such as ionizing radiation or internal events like oxidative damage can cause DNA double stranded breaks (DSBs) [1,2]. DSBs are also part of the normal lymphocyte developmental program where they are an integral element of the mechanisms that generate a diverse immune repertoire in the context of V(D)J and immunoglobulin heavy chain (IgH) class switch recombination (CSR) [3-5]. DSBs initiate a cascade of cellular events that direct cells to pause and properly repair potentially lethal chromosomal breaks. Errors in the repair of both general and lymphocyte-specific DSBs can lead to oncogenic chromosomal translocations [6-8]. Here, we review recent advances in understanding factors and protein complexes involved in the response to DNA DSBs with a focus on the B lymphocyte specific process of CSR. (c) 2006 Published by Elsevier B.V. C1 Harvard Univ, Sch Med, Joint Program Transfus Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Manis, JP (reprint author), Harvard Univ, Sch Med, Joint Program Transfus Med, 1 Blackfan Circle,Karp 10216, Boston, MA 02115 USA. EM manis@enders.tch.harvard.edu FU NCI NIH HHS [P01CA092615]; NIAID NIH HHS [P01AI031541] NR 130 TC 61 Z9 62 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 8 PY 2006 VL 5 IS 9-10 BP 1030 EP 1041 DI 10.1016/j.dnarep.2006.05.024 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 087EH UT WOS:000240725000005 PM 16934538 ER PT J AU Gurtan, AM D'Andrea, AD AF Gurtan, Allan M. D'Andrea, Alan D. TI Dedicated to the core: Understanding the Fanconi anemia complex SO DNA REPAIR LA English DT Article DE Fanconi anemia; E3 ligase; DNA repair; mono-ubiquitination ID ANAPHASE-PROMOTING COMPLEX; DNA-DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION; NUCLEAR ACCUMULATION; BRCA PATHWAY; CROSS-LINKS; CELL-CYCLE; S-PHASE; PROTEIN; GENE AB The Fanconi anemia (FA) pathway consists of a unique, multi-subunit E3 ubiquitin ligase complex that is activated in a replication and DNA-damage dependent mechanism. This FA core complex possesses a putative case an an E3 ubiquitin ligase subunit, is assembled in both the nucleoplasm and in chromatin, and is required for the mono-ubiquitination of FANCD2, a downstream FA protein, following genotoxic stress. Clinically, absence of the FA pathway results in congenital defects, bone marrow failure, and cancer predisposition. At the cellular level, this pathway is required for chromosomal stability and cellular resistance to DNA interstrand crosslinkers (ICLs) such as mitomycin C (MMC). A general model has emerged for the FA pathway as an arm of the DNA-damage response following ICLs. This review will summarize the current understanding of the FA core complex and propose a model for its activity. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,M640, Boston, MA 02115 USA. EM Alan_Dandrea@dfci.harvard.edu NR 64 TC 39 Z9 40 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 8 PY 2006 VL 5 IS 9-10 BP 1119 EP 1125 DI 10.1016/j.dnarep.2006.05.009 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 087EH UT WOS:000240725000013 PM 16784902 ER PT J AU Nelson, EA Walker, SR Li, W Liu, XS Frank, DA AF Nelson, Erik A. Walker, Sarah R. Li, Wei Liu, X. Shirley Frank, David A. TI Identification of human STAT5-dependent gene regulatory elements based on interspecies homology SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NATURAL-KILLER-CELLS; ADHESION MOLECULE; BINDING-SITES; SIGNAL TRANSDUCER; STAT PROTEINS; ONCOSTATIN M; IFN-ALPHA; NK CELLS; EXPRESSION; TRANSCRIPTION AB STAT5 is a transcription factor essential for hematopoietic physiology. STAT5 functions to transduce signals from cytokines to the nucleus where it regulates gene expression. Although several important transcriptional targets of STAT5 are known, most remain unidentified. To identify novel STAT5 targets, we searched chromosomes 21 and 22 for clusters of STAT5 binding sites contained within regions of interspecies homology. We identified four such regions, including one with tandem STAT5 binding sites in the first intron of the NCAM2 gene. Unlike known STAT5 binding sites, this site is found within a very large intron and resides similar to 200 kb from the first coding exon of NCAM2. We demonstrate that this region confers STAT5-dependent transcriptional activity. We show that STAT5 binds in vivo to the NCAM2 intron in the NKL natural killer cell line and that this binding is induced by cytokines that activate STAT5. Neither STAT1 nor STAT3 bind to this region, despite sharing a consensus binding sequence with STAT5. Activation of STAT4 and STAT5 causes the accumulation of both of these STATs to the NCAM2 regulatory region. Therefore, using an informatics based approach to identify STAT5 targets, we have identified NCAM2 as both a STAT4- and STAT5-regulated gene, and we show that its expression is regulated by cytokines essential for natural killer cell survival and differentiation. This strategy may be an effective way to identify functional binding regions for transcription factors with known cognate binding sites anywhere in the genome. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Sch Publ Hlth, Boston, MA 02115 USA. RP Frank, DA (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu RI Li, Wei/A-8544-2009 FU NHGRI NIH HHS [R01 HG004069, R01 HG004069-01] NR 45 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26216 EP 26224 DI 10.1074/jbc.M605001200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500038 PM 16840779 ER PT J AU Gonzalez, RR Cherfils, S Escobar, M Yoo, JH Carino, C Styer, AK Sullivan, BT Sakamoto, H Olawaiye, A Serikawa, T Lynch, MP Rueda, BR AF Gonzalez, Ruben R. Cherfils, Salandre Escobar, Maria Yoo, Jin H. Carino, Cecilia Styer, Aaron K. Sullivan, Brian T. Sakamoto, Hideo Olawaiye, Alex Serikawa, Takehiro Lynch, Maureen P. Rueda, Bo R. TI Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; FEMALE MICE; UP-REGULATION; CYCLIN D1; PROLIFERATION; ACTIVATION; SEQUENCES; ISOFORMS; PEPTIDE; CASCADE AB To gain insight into the mechanism(s) by which leptin contributes to mammary tumor (MT) development we investigated the effects of leptin, kinase inhibitors, and/or leptin receptor antagonists (LPrA2) on 4T1 mouse mammary cancer cells in vitro and LPrA2 on 4T1-MT development in vivo. Leptin increases the expression of vascular endothelial growth factor (VEGF), its receptor (VEGF-R2), and cyclin D1 through phosphoinositide 3-kinase, Janus kinase 2/signal transducer and activator of transcription 3, and/or extracellular signal-activated kinase 1/2 signaling pathways. In contrast to leptin-induced levels of cyclin D1 the changes in VEGF or VEGF-R2 were more dependent on specific signaling pathways. Incubation of 4T1 cells with anti-VEGF-R2 antibody increased leptin-mediated VEGF expression suggesting an autocrine/paracrine loop. Pretreatment of syngeneic mice with LPrA2 prior to inoculation with 4T1 cells delayed the development and slowed the growth of MT (up to 90%) compared with controls. Serum VEGF levels and VEGF/VEGF-R2 expression in MT were significantly lower in mice treated with LPrA2. Interestingly, LPrA2-induced effects were more pronounced in vivo than in vitro suggesting paracrine actions in stromal, endothelial, and/or inflammatory cells that may impact the growth of MT. Although all the mechanism(s) by which leptin contributes to tumor development are unknown, it appears leptin stimulates an increase in cell numbers, and the expression of VEGF/VEGF-R2. Together, these results provide further evidence suggesting leptin is a MT growth-promoting factor. The inhibition of leptin signaling could serve as a potential adjuvant therapy for treatment of breast cancer and/or provide a new target for the designing strategies to prevent MT development. C1 Boston Biomed Res Inst, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rueda, BR (reprint author), Morehouse Sch Med, 720 Westview Dr, Atlanta, GA 30310 USA. EM brueda@partners.org NR 40 TC 127 Z9 135 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26320 EP 26328 DI 10.1074/jbc.M601991200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500049 PM 16825198 ER PT J AU Thomas, AV Herl, L Spoelgen, R Hiltunen, M Jones, PB Tanzi, RE Hyman, BT Berezovska, O AF Thomas, Anne V. Herl, Lauren Spoelgen, Robert Hiltunen, Mikko Jones, Phill B. Tanzi, Rudolph E. Hyman, Bradley T. Berezovska, Oksana TI Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate reader SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-SECRETASE ACTIVITY; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; CAENORHABDITIS-ELEGANS; MEMBRANE TOPOLOGY; SEL-12 PRESENILIN; ENDOPROTEOLYSIS; CONFORMATION; ASSOCIATION; NICASTRIN AB Presenilin 1 (PS1) in its active heterodimeric form is the catalytic center of the gamma-secretase complex, an enzymatic activity that cleaves amyloid precursor protein (APP) to produce amyloid beta (A beta). Ubiquilin 1 is a recently described PS1 interacting protein, the overexpression of which increases PS1 holoprotein levels and leads to reduced levels of functionally active PS1 heterodimer. In addition, it has been suggested that splice variants of the UBQLN1 gene are associated with an increased risk of developing Alzheimer disease ( AD). However, it is still unclear whether PS1 and ubiquilin 1 interact when expressed at endogenous levels under normal physiological conditions. Here, we employ three novel fluorescence resonance energy transfer-based techniques to investigate the interaction between PS1 and ubiquilin 1 in intact cells. We consistently find that the ubiquilin 1N terminus is in close proximity to several epitopes on PS1. We show that ubiquilin 1 interacts both with PS1 holoprotein and heterodimer and that the interaction between PS1 and ubiquilin 1 takes place near the cell surface. Furthermore, we show that the PS1-ubiquilin 1 interaction can be detected between endogenous proteins in primary neurons in vitro as well as in brain tissue of healthy controls and Alzheimer disease patients, providing evidence of its physiological relevance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Berezovska, O (reprint author), Dept Neurol, Alzheimers Unit, 114 16th St, Charlestown, MA 02129 USA. EM oberezovska@partners.org OI Jones, Phillip/0000-0003-0525-6323 FU NIA NIH HHS [5 P01 AG015379-08] NR 32 TC 19 Z9 20 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2006 VL 281 IS 36 BP 26400 EP 26407 DI 10.1074/jbc.M601085200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500057 PM 16815845 ER PT J AU Zeng, WQ Gillis, T Hakky, M Djousse, L Myers, RH MacDonald, ME Gusella, JF AF Zeng, Wenqi Gillis, Tammy Hakky, Michael Djousse, Luc Myers, Richard H. MacDonald, Marcy E. Gusella, James F. TI Genetic analysis of the GRIK2 modifier effect in Huntington's disease SO BMC NEUROSCIENCE LA English DT Article ID AGE-OF-ONSET; NATURAL-HISTORY; GLUR6; REPEAT; HD; CHANNELS AB Background: In Huntington's disease (HD), age at neurological onset is inversely correlated with the length of the CAG trinucleotide repeat mutation, but can be modified by genetic factors beyond the HD gene. Association of a relatively infrequent 16 TAA allele of a trinucleotide repeat polymorphism in the GRIK2 3'UTR with earlier than expected age at neurological onset has been suggested to reflect linkage disequilibrium with a functional polymorphism in GRIK2 or an adjacent gene. Results: We have tested this hypothesis by sequencing all GRIK2 exons, the exon-flanking sequences and 3'UTR in several individuals who were crucial to demonstrating the modifier effect, as they showed much earlier age at neurological onset than would be expected from the length of their HD CAG mutation. Though ten known SNPs were detected, no sequence variants were found in coding or adjacent sequence that could explain the modifier effect by linkage disequilibrium with the 16 TAA allele. Haplotype analysis using microsatellites, known SNPs and new variants discovered in the 3'UTR argues against a common ancestral origin for the 16 TAA repeat alleles in these individuals. Conclusion: These data suggest that the modifier effect is actually due to the TAA repeat itself, possibly via a functional consequence on the GRIK2 mRNA. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM wzeng@coh.org; gillis@helix.mgh.harvard.edu; mhakky@partners.org; ldjousse@rics.bwh.harvard.edu; rmyers@bu.edu; macdonam@helix.mgh.harvard.edu; gusella@helix.mgh.harvard.edu RI Djousse, Luc/F-5033-2017; OI Djousse, Luc/0000-0002-9902-3047; Myers, Richard/0000-0002-8365-2674 FU NINDS NIH HHS [NS16367, P50 NS016367] NR 35 TC 8 Z9 8 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD SEP 7 PY 2006 VL 7 AR 62 DI 10.1186/1471-2202-7-62 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 096KP UT WOS:000241376300001 PM 16959037 ER PT J AU Burgess, SJ Selzer, A Kelly, JX Smilkstein, MJ Riscoe, MK Peyton, DH AF Burgess, Steven J. Selzer, Audrey Kelly, Jane Xu Smilkstein, Martin J. Riscoe, Michael K. Peyton, David H. TI A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIMALARIAL-DRUGS; RODENT MALARIA; IN-VITRO; TRANSPORTER; CHABAUDI; BINDING; COMBINATIONS; IMIPRAMINE; MECHANISM; PARASITES AB A class of hybrid molecules which we term 'reversed chloroquines' (RCQs) was designed, and a prototype molecule, N'-(7-chloroquinolin-4-yl)-N-[3-(10,11-dihydrodibenzo[b, f] azepin-5-yl)propyl]-N-methylpropane1,3- diamine ( 1), was synthesized and tested against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. An in vitro assay against the two strains indicated that 1 was effective at low-nM concentrations against both strains. A preliminary study in mice demonstrated oral efficacy against P. chabaudi and the absence of obvious toxicity. The RCQ approach therefore appears to be feasible. C1 Portland State Univ, Dept Chem, Portland, OR 97207 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Peyton, DH (reprint author), Portland State Univ, Dept Chem, POB 751, Portland, OR 97207 USA. EM peytond@pdx.edu FU NIAID NIH HHS [R21 AI067837, R21 AI067837-01A2] NR 28 TC 83 Z9 88 U1 0 U2 10 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 SEP 7 PY 2006 VL 49 IS 18 BP 5623 EP 5625 DI 10.1021/jm060399n PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079AX UT WOS:000240149000026 PM 16942036 ER PT J AU Sasaki, Y Rajimehr, R Kim, BW Ekstrom, LB Vanduffel, W Tootell, RBH AF Sasaki, Yuka Rajimehr, Reza Kim, Byoung Woo Ekstrom, Leeland B. Vanduffel, Wim Tootell, Roger B. H. TI The radial bias: A different slant on visual orientation sensitivity in human and nonhuman primates SO NEURON LA English DT Article ID SURFACE-BASED ANALYSIS; STRIATE CORTEX; PERIPHERAL-VISION; SPATIAL-FREQUENCY; RECEPTIVE-FIELDS; CONTRAST AGENT; GANGLION-CELLS; FUNCTIONAL MRI; DORSAL V4; AREAS AB It is generally assumed that sensitivity to different stimulus orientations is mapped in a globally equivalent fashion across primate visual cortex, at a spatial scale larger than that of orientation columns. However, some evidence predicts instead that radial orientations should produce higher activity than other orientations, throughout visual cortex. Here, this radial orientation bias was robustly confirmed using (1) human psychophysics, plus fMRI in (2) humans and (3) behaving monkeys. In visual cortex, fMRI activity was at least 20% higher in the retinotopic representations of polar angle which corresponded to the radial stimulus orientations (relative to tangential). In a global demonstration of this, we activated complementary retinotopic quadrants of visual cortex by simply changing stimulus orientation, without changing stimulus location in the visual field. This evidence reveals a neural link between orientation sensitivity and the cortical retinotopy, which have previously been considered independent. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martios Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. CALTECH, ERATO Shimojo Implicit Brain Funct Project, Pasadena, CA 91125 USA. MIT, Cambridge, MA 02139 USA. RP Sasaki, Y (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martios Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM yuka@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR 14075]; NEI NIH HHS [R01 EY017081]; NIBIB NIH HHS [EB 00790]; NIMH NIH HHS [MH 67529] NR 54 TC 99 Z9 99 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 7 PY 2006 VL 51 IS 5 BP 661 EP 670 DI 10.1016/j.neuron.2006.07.021 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 085RZ UT WOS:000240623400014 PM 16950163 ER PT J AU Levine, RJ Lam, C Qian, C Yu, KF Maynard, SE Sachs, BP Sibai, BM Epstein, FH Romero, R Thadhani, R Karumanchi, SA AF Levine, Richard J. Lam, Chun Qian, Cong Yu, Kai F. Maynard, Sharon E. Sachs, Benjamin P. Sibai, Baha M. Epstein, Franklin H. Romero, Roberto Thadhani, Ravi Karumanchi, S. Ananth CA CPEP Study Grp TI Soluble endoglin and other circulating antiangiogenic factors in preeclampsia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; ANGIOGENIC FACTORS; PREGNANCY; RISK; RECEPTOR; WOMEN; HYPERTENSION; TRIAL; PATHOPHYSIOLOGY AB Background: Alterations in circulating soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a proangiogenic protein, appear to be involved in the pathogenesis of preeclampsia. Since soluble endoglin, another antiangiogenic protein, acts together with sFlt1 to induce a severe preeclampsia-like syndrome in pregnant rats, we examined whether it is associated with preeclampsia in women. Methods: We performed a nested case-control study of healthy nulliparous women within the Calcium for Preeclampsia Prevention trial. The study included all 72 women who had preterm preeclampsia (<37 weeks), as well as 480 randomly selected women - 120 women with preeclampsia at term (at >= 37 weeks), 120 women with gestational hypertension, 120 normotensive women who delivered infants who were small for gestational age, and 120 normotensive controls who delivered infants who were not small for gestational age. Results: Circulating soluble endoglin levels increased markedly beginning 2 to 3 months before the onset of preeclampsia. After the onset of clinical disease, the mean serum level in women with preterm preeclampsia was 46.4 ng per milliliter, as compared with 9.8 ng per milliliter in controls (P<0.001). The mean serum level in women with preeclampsia at term was 31.0 ng per milliliter, as compared with 13.3 ng per milliliter in controls (P<0.001). Beginning at 17 weeks through 20 weeks of gestation, soluble endoglin levels were significantly higher in women in whom preterm preeclampsia later developed than in controls (10.2 ng per milliliter vs. 5.8 ng per milliliter, P<0.001), and at 25 through 28 weeks of gestation, the levels were significantly higher in women in whom term preeclampsia developed than in controls (8.5 ng per milliliter vs. 5.9 ng per milliliter, P<0.001). An increased level of soluble endoglin was usually accompanied by an increased ratio of sFlt1:PlGF. The risk of preeclampsia was greatest among women in the highest quartile of the control distributions for both biomarkers but not for either biomarker alone. Conclusions: Rising circulating levels of soluble endoglin and ratios of sFlt1:PlGF herald the onset of preeclampsia. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Ctr Vasc Biol, Boston, MA 02215 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Mol & Vasc Med Div, Ctr Vasc Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Allied Technol Grp, Rockville, MD USA. George Washington Univ, Sch Med, Dept Med, Washington, DC USA. Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, Cincinnati, OH 45267 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Levine, RJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Ctr Vasc Biol, 330 Brookline Ave,RW 663B, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL-079594]; NICHD NIH HHS [N01-HD-3123, N01-HD-1-3121, N01-HD-3122, N01-HD-3124, N01-HD-3125, N01-HD-3126, N01-HD-3154, N01-HD-5-3246, R01 HD-39223]; NIDDK NIH HHS [R01 DK-065997, R01 DK-67397] NR 36 TC 861 Z9 911 U1 4 U2 38 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 7 PY 2006 VL 355 IS 10 BP 992 EP 1005 DI 10.1056/NEJMoa055352 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 080UF UT WOS:000240273300005 PM 16957146 ER PT J AU Ishii, Y Pirkmaier, A Alvarez, JV Frank, DA Keselman, I Logothetis, D Mandeli, J O'Connell, MJ Waxman, S Germain, D AF Ishii, Yuki Pirkmaier, Andreja Alvarez, James V. Frank, David A. Keselman, Inna Logothetis, Diomedes Mandeli, John O'Connell, Matthew J. Waxman, Samuel Germain, Doris TI Cyclin D1 overexpression and response to bortezomib treatment in a breast cancer model SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROTEASOME INHIBITOR PS-341; ACTIVATED SIGNAL TRANSDUCER; MANTLE CELL LYMPHOMA; NF-KAPPA-B; ENDOPLASMIC-RETICULUM; MULTIPLE-MYELOMA; APOPTOSIS; STAT3; EXPRESSION; INDUCTION AB Background. Cyclin D1 is frequently overexpressed in breast cancer, and its overexpression is, surprisingly, associated with improved survival. One potential mechanism for this association involves signal transducer and activator of transcription 3 (STAT3). Methods: Cyclin D1 and STAT3 expression were assessed in human tumors using microarray analysis and in breast cancer cell lines HBL100, T471), MCF7, MDAN113-453, and BT20 and in HBL100 and T47D cells stably overexpressing cyclin D1 using immunoblot analysis. Cyclin D1 protein was stabilized by treatment with the proteasome inhibitor bortezomib, and the effects on STAT3 expression in vitro was determined by using immunoblotting and on xenograft tumor growth and apoptosis in vivo was determined by using terminal deoxyuridine nick-end labeling assays. All statistical tests were two-sided. Results: Tumors with high cyclin D1 expression (n = 17) had low STAT3 expression (mean = 274 arbitrary units), and those with low cyclin D1 expression (n = 31) had high STAT3 expression (mean = 882 arbitrary units) (P <.001). In HBL100 and T47D parental and cyclin D1-overexpressing cells, cyclin D1 overexpression was also inversely associated with STAT3 expression, and cyclin D1 directly reduced the expression of STAT3. Stabilization of cyclin D1 protein by bortezomib treatment further amplified the cyclin D1-dependent repression of STAT3 in vitro and slowed tumor growth in vivo (week 7: untreated mean = 185.7 mm(3) versus treated mean = 136.2 mm(3), difference = 49.5 mm(3), 95% confidence interval [CI] = 18 to 81 mm(3), P=.007; week 8: untreated mean = 240.2 mm(3) versus treated mean = 157.3 mm(3), difference = 82.9 mm(3), 95% CI = 9.1 to 156.7 mm(3), p =.0014; and week 9: untreated mean = 256.4 mm(3) versus treated mean = 170.2 mm(3), difference = 86.2 mm(3), 95% CI = 22.8 to 149.6 mm(3), P =.006) and increased apoptosis (untreated mean = 19% versus treated mean = 54%, difference = 35%, 95% CI = 24.7% to 45.4%; P =.013) of xenograft tumors. Conclusions: Cyclin D1 repression of STAT3 expression may explain the association between cyclin D1 overexpression and improved outcome in breast cancer. In addition, bortezomib can amplify the proapoptotic function of cyclin D1, raising the possibility that cyclin D1 levels may be a marker for predicting the response to this novel drug. C1 Mt Sinai Sch Med, Div Hematol Oncol, Dept Med, New York, NY 10029 USA. Peter MacCallum Canc Ctr, Trescowthick Res Labs, Melbourne, Vic, Australia. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Biomath Sci, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. RP Germain, D (reprint author), Mt Sinai Sch Med, Div Hematol Oncol, Dept Med, 1 Gustave L Levy Pl,Box 1178, New York, NY 10029 USA. EM doris.germain@mssm.edu FU NCI NIH HHS [CA100076, CA109482] NR 39 TC 36 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 6 PY 2006 VL 98 IS 17 BP 1238 EP 1247 DI 10.1093/jnci/djj334 PG 10 WC Oncology SC Oncology GA 101EF UT WOS:000241721000014 PM 16954476 ER PT J AU McGinnis, JM Birt, DF Brannon, PM Carroll, RJ Gibbons, RD Hazzard, WR Kamerow, DB Levin, B Ntambi, JM Paneth, N Rogers, D Saftlas, AF Vaughan, W AF McGinnis, J. Michael Birt, Diane F. Brannon, Patsy M. Carroll, Raymond J. Gibbons, Robert D. Hazzard, William R. Kamerow, Douglas B. Levin, Bernard Ntambi, James M. Paneth, Nigel Rogers, Douglas Saftlas, Audrey F. Vaughan, William CA NIH State of Science TI National Institutes of Health state-of-the-science conference statement: Multivitamin/mineral supplements and chronic disease prevention SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; NUTRITION INTERVENTION TRIALS; AGE-RELATED CATARACT; BETA-CAROTENE; VITAMIN-E; CARDIOVASCULAR-DISEASE; ALPHA-TOCOPHEROL; LUNG-CANCER; COLORECTAL-CANCER; PROSTATE-CANCER C1 Natl Acad, Inst Med, Washington, DC USA. Iowa State Univ, Dept Food Sci & Human Nutr, Ctr Res Bot Dietary Supplements, Ames, IA USA. Iowa State Univ, Coll Agr, Ames, IA USA. Iowa State Univ, Coll Human Sci, Ames, IA USA. Cornell Univ, Div Nutrit Sci, Ithaca, NY USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. Univ Illinois, Ctr Hlth Stat, Chicago, IL USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Georgetown Univ, Washington, DC USA. RTI Int, Washington, DC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. Univ Wisconsin, Dept Nutrit Sci, Madison, WI 53705 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Cleveland Clin, Sect Pediat & Adolescent Endocrinol, Cleveland, OH 44106 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Consumers Union, Washington, DC USA. NIH, Bethesda, MD 20892 USA. RP McGinnis, JM (reprint author), Natl Acad, Inst Med, Washington, DC USA. NR 27 TC 56 Z9 58 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 5 PY 2006 VL 145 IS 5 BP 364 EP 371 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 080NZ UT WOS:000240255900007 ER PT J AU Wu, MT Tseng, WYI Su, MYM Liu, CP Chiou, KR Wedeen, VJ Reese, TG Yang, CF AF Wu, Ming-Ting Tseng, Wen-Yih I. Su, Mao-Yuan M. Liu, Chun-Peng Chiou, Kuan-Rau Wedeen, Van J. Reese, Timothy G. Yang, Chien-Fang TI Diffusion tensor magnetic resonance imaging mapping the fiber architecture remodeling in human myocardium after infarction - Correlation with viability and wall motion SO CIRCULATION LA English DT Article DE myocardial infarction; remodeling; magnetic resonance imaging ID LEFT-VENTRICULAR MYOCARDIUM; CANINE LEFT-VENTRICLE; WATER DIFFUSION; IN-VIVO; ENGINEERING MECHANICS; SUCCESSIVE STATES; MODEL; MRI; RAT; ORIENTATION AB Background - Diffusion tensor magnetic resonance imaging (DT-MRI) provides a means for nondestructive characterization of myocardial architecture. We used DT-MRI to investigate changes in direction-dependent water diffusivity to reflect alterations in tissue integrity (trace apparent diffusion coefficients [ADCs] and fractional anisotropy [FA]), as well as indicators of remodeling of fiber helix angles, in patients after myocardial infarction. Methods and Results - Thirty-seven patients (35 men, 2 women; median age, 59) after acute myocardial infarction (median interval from onset, 26 days) were enrolled. DT-MRI was performed at the midventricular level to measure trace ADC, FA, and helix angles of myofibers. Helix angles were grouped into left-handed helical fibers, circumferential fibers, and right-handed helical fibers. Measurements were correlated with viability and regional wall motion assessed by contrast-delay-enhancement and cine MRI, respectively. The infarct zone showed significantly increased trace ADC and decreased FA than the remote zone. The percentage of left-handed helical fibers increased from the remote zone (mean +/- SD, 13.3 +/- 5.8%) to the adjacent zone (19.2 +/- 9.7%) and infarct zone (25.8 +/- 18.4%) (MANOVA, P = 0.004). The percentage of right-handed helical fibers decreased from the remote zone (35.0 +/- 9.0%) to the adjacent zone (25.5 +/- 11.5%) and infarct zone (15.9 +/- 9.2%) (P < 0.001). Multiple linear regression showed that the percentage of left-handed helical fibers of the infarct zone was the strongest correlate of infarct size and predictor of ejection fraction. Conclusions - In vivo DT-MRI of postinfarct myocardium revealed a significant increase in trace ADC and a decrease in FA, indicating altered tissue integrity. The redistribution of fiber architecture correlated with infarct size and left ventricular function. This technique may help us understand structural correlates of functional remodeling after infarction. C1 Kaohsiung Vet Gen Hosp, Dept Radiol, Sect Thorac & Circulat Imaging, Kaohsiung 813, Taiwan. Kaohsiung Vet Gen Hosp, Dept Med, Kaohsiung, Taiwan. Natl Yang Ming Univ, Fac Med, Sch Med, Taipei 112, Taiwan. Natl Yang Ming Univ, Inst Biomed Engn, Taipei 112, Taiwan. Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Med Imaging, Taipei, Taiwan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. Fooyin Univ, Dept Nutr & Hlth Sci, Kaohsiung, Taiwan. RP Wu, MT (reprint author), Kaohsiung Vet Gen Hosp, Dept Radiol, Sect Thorac & Circulat Imaging, 386 Ta Chung 1st Rd, Kaohsiung 813, Taiwan. EM wu.mingting@gmail.com OI SU, MAO-YUAN/0000-0002-6699-2298; Tseng, Wen-Yih Isaac/0000-0002-2314-6868 NR 36 TC 139 Z9 148 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 5 PY 2006 VL 114 IS 10 BP 1036 EP 1045 DI 10.1161/CIRCULATIONHAHA.105.545863 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 080JV UT WOS:000240244700008 PM 16940196 ER PT J AU Park, YK Popescu, G Badizadegan, K Dasari, RR Feld, MS AF Park, YongKeun Popescu, Gabriel Badizadegan, Kamran Dasari, Ramachandra R. Feld, Michael S. TI Diffraction phase and fluorescence microscopy SO OPTICS EXPRESS LA English DT Article ID DYNAMICS; CELLS; INTERFEROMETER; SUBWAVELENGTH; LIGHT AB We have developed diffraction phase and fluorescence (DPF) microscopy as a new technique for simultaneous quantitative phase imaging and epi-fluorescence investigation of live cells. The DPF instrument consists of an interference microscope, which is incorporated into a conventional inverted fluorescence microscope. The quantitative phase images are characterized by sub-nanometer optical path-length stability over periods from milliseconds to a cell lifetime. The potential of the technique for quantifying rapid nanoscale motions in live cells is demonstrated by experiments on red blood cells, while the composite phase-fluorescence imaging mode is exemplified with mitotic kidney cells. (c) 2006 Optical Society of America C1 MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Park, YK (reprint author), MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. EM gpopescu@mit.edu RI Park, YongKeun/B-9017-2009 NR 24 TC 124 Z9 129 U1 4 U2 20 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 4 PY 2006 VL 14 IS 18 BP 8263 EP 8268 DI 10.1364/OE.14.008263 PG 6 WC Optics SC Optics GA 083MN UT WOS:000240460100031 PM 19529201 ER PT J AU Wirth, L Allen, AM Machtay, M AF Wirth, Lori Allen, Aaron M. Machtay, Mitchell TI Altered fractionation: a fractional benefit? SO LANCET LA English DT Editorial Material ID ADVANCED LARYNGEAL-CANCER; SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; PHASE-III; NECK-CANCER; ACCELERATED FRACTIONATION; RANDOMIZED-TRIAL; RADIOTHERAPY; HEAD; CHEMOTHERAPY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Wirth, L (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Lori_Wirth@dfci.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 2 PY 2006 VL 368 IS 9538 BP 819 EP 821 DI 10.1016/S0140-6736(06)69300-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 082FD UT WOS:000240371200005 PM 16950339 ER PT J AU Singh, AK Gervais, DA Lee, P Westra, S Hahn, PF Novelline, RA Mueller, PR AF Singh, A. K. Gervais, D. A. Lee, P. Westra, S. Hahn, P. F. Novelline, R. A. Mueller, P. R. TI Omental infarct: CT imaging features SO ABDOMINAL IMAGING LA English DT Article DE omental infarction; omentum; computed tomography; acute abdomen ID SEGMENTAL INFARCTION; APPENDAGITIS; CHILDREN; TORSION; US AB Background: The aim of this study is to describe contrast-enhanced computed tomographic (CT) features of acute omental infarction and to study the evolutionary changes on follow-up CT imaging. Methods: Fifteen cases of omental infarction were evaluated for their initial CT imaging features. The imaging features evaluated included size of the fatty lesion, location, peripheral rim, and relation to colon. CT findings were correlated with etiology, clinical presentation, and leukocytosis. Follow-up CT images were available in eight patients and the imaging features were studied. Results: Eight omental infarcts were of unknown etiology and seven were secondary to abdominal surgery. In 53% of patients (eight of 15), the location of the omental infarct was in the right lower, mid, or upper quadrants. These eight right-side infarcts occurred in six patients with primary omental infarcts. In 13 of 14 patients who underwent CT within 15 days of onset of omental infarct, the margin of the lesion was ill defined. Primary omental (n = 8) infarcts were seen in younger patients (p = 0.02) and were larger on CT (p = 0.02) compared with secondary omental infarcts. CT findings evolved from an ill-defined, heterogeneous fat-density lesion to a well-defined, heterogeneous fat-density lesion with a peripheral hyperdense rim in all six secondary omental infarctions for which acute stage and follow-up CT images were available for interpretation. Conclusion: There is a significant difference in the age distribution and CT findings in terms of size of the omental infarction between primary and secondary etiologies. On follow-up CT, secondary omental infarcts progressively shrank and developed a well-defined, hyperdense rim around a fatty core. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intevent Emergency Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intevent Emergency Radiol, 55 Fruit St, Boston, MA 02114 USA. EM pallaviajay@hotmail.com NR 15 TC 35 Z9 35 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD SEP-OCT PY 2006 VL 31 IS 5 BP 549 EP 554 DI 10.1007/s00261-005-0251-6 PG 6 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 124YD UT WOS:000243407800007 PM 16465576 ER PT J AU Betancourt, JR AF Betancourt, Joseph R. TI Eliminating racial and ethnic disparities in health care: What is the role of academic medicine? SO ACADEMIC MEDICINE LA English DT Article ID SPANISH-SPEAKING PATIENTS; DECISION-MAKING; LANGUAGE; MANAGEMENT; EMERGENCY; RACE; PHYSICIANS; ACCESS; COMMUNICATION; SATISFACTION AB Research has shown that minority Americans have poorer health outcomes (compared to whites) from preventable and treatable conditions such as cardiovascular disease, diabetes, asthma, and cancer. in addition to racial and ethnic disparities in health, there is also evidence of racial and ethnic disparities in health care. The Institute of Medicine Report Unequal Treatment remains the preeminent study of the issue of racial and ethnic disparities in health care in the United States. Unequal Treatment provided a series of general and specific recommendations to address such disparities in health care, focusing on a broad set of stakeholders including academic medicine. Academic medicine has several important roles in society, including providing primary and specialty medical services, caring for the poor and uninsured, engaging in research, and educating health professionals. Academic medicine should also provide national leadership by identifying innovations and creating solutions to the challenges our health care system faces in its attempt to deliver high-quality care to all patients. Several of the recommendations of Unequal Treatment speak directly to the mission and roles of academic medicine. For instance, patient care can be improved by collecting and reporting data on patients' race/ethnicity; education can minimize disparities by integrating cross-cultural education into health professions training; and research can help improve health outcomes by better identifying sources of disparities and promising interventions. These recommendations have clear and direct implications for academic medicine. Academic medicine must make the elimination of health care disparities a critical part of its mission, and provide national leadership by identifying quality improvement innovations and creating disparities solutions. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dispar Solut Ctr, Boston, MA USA. Inst Hlth Policy, Boston, MA USA. RP Betancourt, JR (reprint author), Harvard Univ, Sch Med, 50 Staniford St,Ste 942, Boston, MA 02114 USA. EM jbetancourt@partners.org NR 56 TC 57 Z9 58 U1 3 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2006 VL 81 IS 9 BP 788 EP 792 DI 10.1097/00001888-200609000-00004 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 080NG UT WOS:000240254000004 PM 16936481 ER PT J AU Blumenthal, D Ferris, TG AF Blumenthal, David Ferris, Timothy G. TI Safety in the academic medical center: Transforming challenges into ingredients for improvement SO ACADEMIC MEDICINE LA English DT Article ID ADVERSE EVENTS; TEACHING HOSPITALS; CARE; QUALITY; ERRORS AB Patient safety has emerged as an important challenge to the leadership of academic medical centers (i.e., teaching hospitals with significant research activity). This article describes the evidence regarding patient safety at academic medical centers (AMCs) and the special circumstances of AMCs that create challenges and opportunities for making improvements. While the research on the relative safety of patients in AMCs compared to other types of hospitals is sparse, it seems clear that AMCs in general do not stand out as models of patient safety. AMCs are unique as health care providers because of the multiple consequences of their three missions: patient care, research, and teaching. Aspects of these missions can serve to both enhance an AMC's ability to address safety issues and at the same time create unique and challenging barriers. For example, the research enterprise may distract managers' focus on safety issues but at the same time provide a wealth of highly trained talent for investigating and reducing safety problems. By addressing these challenges, AMCs have the opportunity, even the obligation, to be both the source of new knowledge on health care safety as well as the transmitter of new skills in safe patient care for the health care providers of the future. C1 Massachusetts Gen Hosp & Partners Hlth Syst, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp & Partners Hlth Syst, Inst Hlth Policy, 55 Fruit St, Boston, MA 02114 USA. EM dblumenthal@partners.org NR 30 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2006 VL 81 IS 9 BP 817 EP 822 DI 10.1097/00001888-200609000-00010 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 080NG UT WOS:000240254000010 PM 16936489 ER PT J AU Riemenschneider, MJ Betensky, RA Louis, DN AF Riemenschneider, M. J. Betensky, R. A. Louis, D. N. TI AKT activation in human glioblastomas enhances proliferation via TSC2 and S6 kinase signalling SO ACTA NEUROPATHOLOGICA LA English DT Meeting Abstract CT 51st Annual Meeting of the German-Society-of-Neuropathology-and-Neuroanatomy CY SEP 20-24, 2006 CL Mannheim, GERMANY SP German Soc Neuropathol & Neuroanat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Canc, Mol Pathol Unit, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD SEP PY 2006 VL 112 IS 3 BP 373 EP 373 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 077WB UT WOS:000240061000072 ER PT J AU Clements, KM Murphy, JM Eisen, SV Normand, SLT AF Clements, Karen M. Murphy, Jane M. Eisen, Susan V. Normand, Sharon-Lise T. TI Comparison of self-report and clinician-rated measures of psychiatric symptoms and functioning in predicting 1-year hospital readmission SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE psychiatric rehospitalization self-report; clinician rating; BASIS-32; GAF; multiple informant analysis ID QUALITY-OF-LIFE; GLOBAL ASSESSMENT; INCREMENTAL VALIDITY; MULTIPLE INFORMANTS; OUTCOMES; CARE; SCALE; GAF; REHOSPITALIZATION; RELIABILITY AB This study compared the self-report Behavior and Symptom Identification Scale (BASIS-32) and. clinician-rated Global Assessment of Functioning (GAF) in their ability to predict a measure of psychiatric outcome, 1-year psychiatric hospital readmission. BASIS-32 and GAF were completed at admission for 1034 patients in an inpatient psychiatric facility. Multiple informants analysis was used to determine the difference between the two in predicting readmission within I year. We also examined sensitivity, specificity, and predictive value positive of the two measures, and whether self-report added information above clinician rating in predicting outcome. While the odds of 1-year readmission decreased with increasing BASIS-32 score, there was no association between change in GAF score and 1-year readmission. Although neither measure used alone demonstrated high predictive value, using both scores improved predictive ability over using clinician rating alone. In this setting, self-report was better than clinician rating in predicting psychiatric outcome. Differences between the two in relation to other outcomes need to be examined. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Dept Publ Hlth, Appl Stat Evaluat & Tech Serv, Boston, MA 02108 USA. Massachusetts Gen Hosp East, Dept Psychiat, Charlestown, MA 02129 USA. RP Clements, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM karen.clements@state.ma.us FU NIMH NIH HHS [5 T32 MH17119-20] NR 43 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2006 VL 33 IS 5 BP 568 EP 577 DI 10.1007/s10488-006-0066-y PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 094HT UT WOS:000241231200007 PM 16799832 ER PT J AU MacIntyre, JC Essock, S Clay, S Zuber, MP Felton, CJ AF MacIntyre, James C., II Essock, Susan Clay, Sally Zuber, Michael P. Felton, Chip J. TI The Kids Oneida project: What happened to services when the payment rules changed SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE children's mental health services; systems of care; wrap-around; finance; payment rules; managed care; program implementation ID OUTCOMES; ADOLESCENTS; CHILDREN; CARE; SYSTEM AB Community-based systems of care may provide high quality, cost-effective alternatives to institutional care for children and adolescents. This report examines Kids Oneida (KO), a not-for-profit managed care entity established in upstate New York in 1998 to serve such children and their families. Changes in payment rules that established the program allowed KO to contract with a wide array of providers to provide and be reimbursed for non-traditional and formerly unreimbursable services, such as mentoring and supervision. By design, emphasis was on highly individualized plans of care in which traditional office-based services played only a small part. During the first 30 months of KO's operation, 228 children, whose severity of emotional disturbances was comparable to those of children placed in residential treatment centers, had average monthly expenditures for first admissions of $2,734 for services and $228 for administrative fees. Median length of stay in the program was 13.5 months, yielding an estimate of $39,987 for typical length of stay. Length of stay and treatment costs were not related to children's gender or race. Length of stay was significantly longer for children with diagnoses indicating attention deficit hyperactivity disorder and behavior disorders. Treatment costs were significantly higher for children with behavior disorders and/or substance use and children who had had prior contact with the juvenile justice system. C1 Carolinas Mental Ctr, Behav Hlth Ctr, Charlotte, NC 28211 USA. NYU, Mt Sinai Sch Med, Dept Psychiat, Div Hlth Serv Res, New York, NY USA. Bronx Vet Adm Med Ctr, MIRECC, Bronx, NY USA. NYU, Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. New York State Off Mental Hlth, Ctr Informat Technol & Evaluat Res, Albany, NY USA. RP MacIntyre, JC (reprint author), Carolinas Mental Ctr, Behav Hlth Ctr, 501 Billingsley Rd, Charlotte, NC 28211 USA. EM james.macintyre@carolinas.org NR 26 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2006 VL 33 IS 5 BP 585 EP 597 DI 10.1007/s10488-006-0065-z PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 094HT UT WOS:000241231200009 PM 16807793 ER PT J AU Young, RH AF Young, Robert H. TI From Krukenberg to today: The ever present problems posed by metastatic tumors in the ovary - Part I. Historical perspective, general principles, mucinous tumors including the Krukenberg tumor SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE ovary; metastasis; history; Krukenberg tumor; mucinous neoplasms ID CLINICOPATHOLOGICAL ANALYSIS; PSEUDOMYXOMA-PERITONEI; DIFFERENTIAL-DIAGNOSIS; ENDOCERVICAL ADENOCARCINOMA; MORPHOLOGIC SPECTRUM; CELL-CARCINOMA; EMPHASIS; ORIGIN; NEOPLASMS; FEATURES AB This review considers historical aspects of metastatic tumors to the ovary, general principles that aid in their evaluation, and metastatic mucinous tumors, including the Krukenberg tumor. The historical timeline on the Krukenberg tumor dates back to the legendary Sir James Paget and the story is followed through the well-known, albeit flawed, contribution of Friedrich Krukenberg and others who have contributed important papers over the years, including the overlooked contribution of the French investigator Gauthier-Villars. Knowledge of metastatic colorectal carcinoma is traced back to the famed British surgeon Sir John Bland-Sutton and followed through to more recent contributions, including the important one of Lash and Hart. Contributions on mucinous tumors conclude the historical perspective, note being made of the recent evidence suggesting that the long held contention of Dr Robert E. Scully that ovarian mucinous tumors in patients with pseudomyxoma peritonei usually originate from the appendix is correct. The section on general principles highlights the many clinical, gross. microscopic.. and special techniques such as immunohistochemistry that may aid in determining that an ovarian tumor is metastatic with emphasis on the first 3 mentioned aspects. Problematic features such as a tendency for metastatic tumors to be cystic, even when the primary tumors are not, and for many metastatic tumors to mature in the ovary (so-called maturation phenomenon), are emphasized. Of the many helpful findings that resolve the problem, the characteristic features of surface implants are highlighted. The contribution on the Krukenberg tumor reviews the varied microscopy of this tumor pointing, out that the well-known pattern of signet-ring cells in a cellular stroma, albeit characteristic, is often not striking and frequently overshadowed by other microscopic features. The latter include, in many cases, a rather unique microcystic pattern. The final portion of the essay reviews mucinous tumors of non-Krukenberg type, beginning with those that originate front the appendix. The appendiceal neoplasms have distinctive features in most cases being particularly well differentiated. and this is also seen in their ovarian metastases. Other mucinous tumors that commonly simulate closely metastatic neoplasms, include those from the pancreas in particular, but also diverse other sites, are then reviewed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. EM ryoung@partners.org NR 70 TC 73 Z9 77 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD SEP PY 2006 VL 13 IS 5 BP 205 EP 227 DI 10.1097/01.pap.0000213038.85704.e4 PG 23 WC Pathology SC Pathology GA 091SY UT WOS:000241049800001 PM 16998315 ER PT J AU Rahemtullah, A Oliva, E AF Rahemtullah, Aliyah Oliva, Esther TI Nephrogenic adenoma: An update on an innocuous but troublesome entity SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE nephrogenic adenoma; urothelium; immunohistochemistry; pathogenesis; differential diagnosis; clear cell carcinoma; urothelial carcinoma; prostatic adenocarcinoma ID CLEAR-CELL ADENOCARCINOMA; RENAL-TRANSPLANT RECIPIENTS; URINARY-BLADDER; NESTED VARIANT; CYTOMEGALOVIRUS-INFECTION; UROTHELIAL CARCINOMA; PROSTATIC URETHRA; METAPLASIA; EXPRESSION; LESION AB Nephrogenic adenoma (NA) is a rare benign lesion of the urothelial tract that is typically preceded by some form of genitourinary insult. The pathogenesis of NA is not entirely clear. Although generally presumed to be a metaplastic process of the urothelium, recent evidence suggests that NA may in fact be derived from detached renal tubular cells implanting along the urothelial tract in previously injured areas, at least in cases associated with a kidney transplant. On light microscopy, NA shows a variety of patterns, including tubulocystic, papillary, and much less frequently solid, that often coexist. Recognition of its characteristic patterns, and awareness of its unusual architectural and cytologic features, is key to making the diagnosis of NA and distinguishing this lesion from malignant neoplasms occurring at the same sites, in particular, clear cell carcinoma, nested or rnicrocystic variants of urothelial carcinoma and prostatic adenocarcinoma. Although straightforward in most cases. the correct diagnosis may be difficult to make on limited tissue samples. A number of immunohistochemical markers have been studied in an attempt to characterize NA; however, to date there is no specific immunohistochemical profile to distinguish this lesion from its malignant mimickers, although PAX2. a new marker, may prove to be helpful in this regard. Clinicopathologic correlation with careful attention to morphology remains the pillar in establishing the correct diagnosis. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rahemtullah, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219,55 Fruit St, Boston, MA 02114 USA. EM arahemtullah@partners.org NR 64 TC 28 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD SEP PY 2006 VL 13 IS 5 BP 247 EP 255 DI 10.1097/01.pap.0000213047.69564.c2 PG 9 WC Pathology SC Pathology GA 091SY UT WOS:000241049800004 PM 16998318 ER PT J AU Crabbe, JC Rhodes, JS AF Crabbe, John C. Rhodes, Justin S. TI Drinking in the dark: A mouse model for high ethanol intake SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT World Congress on Alcohol Research CY SEP 10-13, 2006 CL Sydney, AUSTRALIA SP Int Soc Biomed Res Alcoholism C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2006 VL 30 IS 9 SU S BP 95A EP 95A PG 1 WC Substance Abuse SC Substance Abuse GA 075XE UT WOS:000239919900205 ER PT J AU Mikhak, Z AF Mikhak, Zamaneh TI Dose-response studies of fluticasone propionate and budesonide: Classification based on asthma severity SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 18-22, 2005 CL San Antonio, TX SP Amer Acad Allergy Asthma & Immunol ID TO-MODERATE ASTHMA; QUALITY-OF-LIFE; STEROID-DEPENDENT ASTHMA; INHALED BUDESONIDE; PERSISTENT ASTHMA; DOUBLE-BLIND; INHALATION SUSPENSION; YOUNG-CHILDREN; MILD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS AB There are discrepancies in the results of dose-response studies of inhaled steroids. Although some studies show a dose-response relationship, others show no change in outcome with increasing the dose of inhaled steroids. These discrepancies are partly caused by the heterogeneity of dose-response studies. One area of heterogeneity is the subjects' level of asthma severity at baseline. The objective of this study was to classify dose-response studies of two widely used inhaled steroids for asthma, fluticasone propionate (FP), and budesonide (BUD), according to the subjects' level of asthma severity at baseline. A PubMed search, limited to the English language and human subjects, was conducted from January of 1983 to January of 2004, using "dose response and budesonide" (331 articles) and "dose-response and fluticasone" (211 articles). Bibliographies of selected articles were searched for more references. Articles with at least two doses of the same inhaled steroid and one objective marker of asthma were included, resulting in 29 articles for FP and 32 articles for BUD. Studies vary widely in their assessment and reporting of indicators of asthma severity and control at baseline but could be classified according to the level of steroid use at baseline as an indicator of asthma severity. Studies with all or some patients on oral steroids at baseline consistently showed a dose response. Although heterogeneity of dose-response studies make their classification and interpretation difficult, a dose response was consistently noted when all or some patients were on oral steroids at baseline. C1 Massachusetts Gen Hosp, Childrens Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mikhak, Z (reprint author), Massachusetts Gen Hosp, Childrens Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM zmikhak@partners.org NR 68 TC 3 Z9 4 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 2006 VL 27 IS 5 BP 402 EP 411 DI 10.2500/aap.2006.27.2906 PG 10 WC Allergy SC Allergy GA 142QE UT WOS:000244663900014 PM 17063671 ER PT J AU Charytan, D Mauri, L Agarwal, A Servoss, S Scirica, B Kuntz, RE AF Charytan, David Mauri, Laura Agarwal, Anupam Servoss, Steven Scirica, Benjamin Kuntz, Richard E. TI The use of invasive cardiac procedures after acute myocardial infarction in long-term dialysis patients SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID STAGE RENAL-DISEASE; CORONARY REVASCULARIZATION PROCEDURES; ADMINISTRATIVE DATA; RANDOMIZED-TRIAL; UNSTABLE ANGINA; UNITED-STATES; SURVIVAL; COMORBIDITY; DYSFUNCTION; MORTALITY AB Background Dialysis patients have an excessive risk of cardiovascular death after myocardial infarction (MI). Underutilization of cardiac therapies may partially explain this risk, but whether patients on maintenance dialysis have differential rates of coronary angiography or revascularization during admission for MI compared with patients not on dialysis and whether these differences are explained by the presence of comorbid illness were uncertain. Methods We analyzed 154692 patients with a primary diagnosis of MI in the 2001 National Inpatient Sample, and we compared procedure use in patients on long-term dialysis, patients with non-dialysis-dependent chronic kidney disease (CKD), or normal renal function. Results Dialysis patients and patients with dialysis-independent CKD were significantly less likely to undergo coronary angiography than patients with normal renal function (39% and 34% vs 56%). They were also less likely to undergo coronary revascularization (19% and 23% vs 41%) or to have a coronary intervention after diagnostic angiography (46% and 62% vs 70%). After adjustment, these differences remained, with a lower likelihood of angiography (42% and 45% vs 56%), revascularization (22% and 31% vs 41%), orcoronary intervention after diagnostic angiography (52% and 66% vs 70%). Conclusions Despite a high mortality rate after MI, patients on dialysis are markedly less likely than patients with dialysis-independent CKD or normal renal function to undergo diagnostic angiography or coronary revascularization after admission for MI. Additional studies to determine how these disparities are related to mortality are warranted. C1 Brigham & Womens Hosp, Dept Med, Div Clin Biometr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Charytan, D (reprint author), Brigham & Womens Hosp, Dept Med, Div Clin Biometr, 1 Brigham Circle,3rd Floor, Boston, MA 02115 USA. EM cdcharytan@partners.org FU NIDDK NIH HHS [T32 DK007199, T32 DK007199-25, T32-DK07199-25] NR 26 TC 48 Z9 50 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2006 VL 152 IS 3 BP 558 EP 564 DI 10.1016/j.ahj.2006.02.021 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 084WJ UT WOS:000240564800030 PM 16923431 ER PT J AU Joffe, S AF Joffe, Steven TI Altruistic discourse and therapeutic misconception in research informed consent SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [CA 96872] NR 8 TC 6 Z9 6 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD SEP-OCT PY 2006 VL 6 IS 5 BP 53 EP 54 DI 10.1080/15265160600862924 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 096UE UT WOS:000241401500023 PM 16997830 ER PT J AU Cavusoglu, E Chopra, V Gupta, A Clark, LT Eng, C Marmur, JD AF Cavusoglu, Erdal Chopra, Vineet Gupta, Amit Clark, Luther T. Eng, Calvin Marmur, Jonathan D. TI Usefulness of anemia in men as an independent predictor of two-year cardiovascular outcome in patients presenting with acute coronary syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; DISEASE; ASSOCIATION; MORTALITY; HEART; RISK AB Anemia has been shown to be an independent risk factor for the development of adverse cardiovascular outcomes in a variety of patient populations. In the case of patients presenting with acute coronary syndrome (ACS), anemia has been demonstrated to be a powerful and independent predictor of 30-day outcomes. However, there are limited and conflicting data about the long-term independent predictive value of anemia in patients with ACS. This is in contrast to non-ACS populations in which anemia has been shown to be an independent predictor of long-term outcomes. The present study investigated the long-term prognostic significance of anemia in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography at a Veterans Affairs Medical Center. All patients were followed prospectively for the development of death or acute myocardial infarction (AMI), and follow-up data were available for all patients at 24 months. After controlling for a variety of baseline clinical, laboratory, and angiographic variables, hemoglobin (analyzed as a continuous variable and as a categorical variable using the World Health Organization cutoff of 13 g/dl for men) was a strong and independent predictor of the composite end point of death or AMI at 24 months when using a Cox proportional hazards model. At 24 months, the event-free survival was 64% in the group with a hemoglobin level < 13 g/dl compared with 81% in the group with a hemoglobin level 13 g/dl (p = 0.0065 by log-rank test). In conclusion, these data demonstrate that baseline anemia is a strong and independent predictor of death or AMI at 2 years in patients with ACS. (c) 2006 Elsevier Inc. C1 Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. Bronx Vet Affairs Med Ctr, Dept Med, New York, NY USA. RP Marmur, JD (reprint author), Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. EM jonathan@marmur.com NR 9 TC 38 Z9 45 U1 0 U2 1 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2006 VL 98 IS 5 BP 580 EP 584 DI 10.1016/j.amjcard.2006.03.031 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 081NM UT WOS:000240324300003 PM 16923440 ER PT J AU Lam, MM Clarridge, JE AF Lam, Maggie M. Clarridge, Jill E., III TI The other group G Streptococcus: Increased detection of Streptococcus canis ulcer infections in dog owners. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-and-Scientists CY JUN 01-03, 2006 CL Chicago, IL SP Acad Clin Lab Phys & Sci C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2006 VL 126 IS 3 MA 19 BP 459 EP 460 PG 2 WC Pathology SC Pathology GA 075UK UT WOS:000239910500034 ER PT J AU Chapman, J Pallin, D AF Chapman, Jacob Pallin, Daniel TI Popliteal air following penetrating trauma SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EXTREMITY TRAUMA; PHYSICAL-EXAMINATION; INJURIES; MANAGEMENT C1 Brigham & Womens Hosp, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Emergency Med, Boston, MA 02114 USA. RP Chapman, J (reprint author), Brigham & Womens Hosp, Div Emergency Med, 75 Francis St, Boston, MA 02115 USA. OI Pallin, Daniel/0000-0002-8517-9702 NR 7 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD SEP PY 2006 VL 24 IS 5 BP 638 EP 639 DI 10.1016/j.ajem.2006.01.002 PG 2 WC Emergency Medicine SC Emergency Medicine GA 083ID UT WOS:000240448700027 PM 16938616 ER PT J AU Jensen, DM Pace, SC Soffer, E Comer, GM AF Jensen, Dennis M. Pace, Samuel C. Soffer, Elaine Comer, Gail M. CA 315 Study Grp TI Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: A US Multicenter randomized, double-blind study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BLEEDING PEPTIC-ULCER; PROTON-PUMP INHIBITORS; UPPER GASTROINTESTINAL HEMORRHAGE; HEATER PROBE THERMOCOAGULATION; PLACEBO-CONTROLLED MULTICENTER; NONBLEEDING VISIBLE VESSELS; ENDOSCOPIC THERAPY; ACID SUPPRESSION; INTRAVENOUS OMEPRAZOLE; COMPARATIVE TRIAL AB OBJECTIVES: No North American randomized study has compared ulcer rebleeding rates after endoscopic hemostasis in high-risk patients treated with high-dose intravenous (IV) proton pump inhibitors (PPIs) or IV histamine-2 receptor antagonists. Our hypothesis was that ulcer rebleeding with IV pantoprazole (PAN) would be lower than with IV ranitidine (RAN). METHODS: This was a multicenter, randomized, double-blind, U.S. study. Patients with bleeding peptic ulcers and major stigmata of hemorrhage had endoscopic hemostasis with thermal probes with or without epinephrine injection, then were randomly assigned to IV PAN 80 mg plus 8 mg/h or IV RAN 50 mg plus 6.25 mg/h for 72 h, and subsequently had an oral PPI (1/day). Patients with signs of rebleeding had repeat endoscopy. Rebleeding rates up to 30 days were compared in an intention-to-treat analysis. RESULTS: The study was stopped early because of slow enrollment (total N = 149, PAN 72, RAN 77). Demographics, APACHE II scores, ulcer type/location, stigmata, and hemostasis used were similar. The 7- and 30-day rebleeding rate was 6.9% (5 of 72 patients) with PAN and 14.3% (11 of 77) for RAN (p = 0.19). Rebleeds occurred within 72 h in 56% and between 4 and 7 days in 44% of patients. The 30-day mortality rate was 4%. Nonbleeding severe adverse events were more common in the RAN than in the PAN group (14 [18.1%] vs 7 [9.7%], p = 0.16). CONCLUSIONS: Because of the small sample size of this study, there was an arithmetic but not significant difference in ulcer rebleeding rates. C1 CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Wyeth Pharmaceut, Collegeville, PA USA. RP Jensen, DM (reprint author), CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Bldg 115,Room 318, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [K24 DK02650, P30 DK41301] NR 47 TC 43 Z9 44 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 BP 1991 EP 1999 DI 10.1111/j.1572-0241.2006.00773.x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080ZM UT WOS:000240287000009 PM 16968504 ER PT J AU Kanwal, F Farid, M Martin, P Chen, G Gralnek, IM Dulai, GS Spiegel, BMR AF Kanwal, Fasiha Farid, Mary Martin, Paul Chen, Gary Gralnek, Ian M. Dulai, Gareth S. Spiegel, Brennan M. R. TI Treatment alternatives for hepatitis B cirrhosis: A cost-effectiveness analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID LONG-TERM LAMIVUDINE; LAMIVUDINE/INTERFERON COMBINATION THERAPY; SEVERELY DECOMPENSATED CIRRHOSIS; LIVER-TRANSPLANT RECIPIENT; IMMUNE GLOBULIN; ADEFOVIR DIPIVOXIL; HEPATOCELLULAR-CARCINOMA; NATURAL-HISTORY; NUCLEOSIDE-NAIVE; SURFACE-ANTIGEN AB BACKGROUND: Hepatitis B virus (HBV) patients with cirrhosis are at risk for developing costly, morbid, or mortal events, and therefore need highly effective therapies. Lamivudine is effective but is limited by viral resistance. In contrast, adefovir and entecavir have lower viral resistance, but are more expensive. The most cost-effective approach is uncertain. METHODS: We evaluated the cost-effectiveness of six strategies in HBV cirrhosis: (1) No HBV treatment ("do nothing"), (2) lamivudine monotherapy, (3) adefovir monotherapy, (4) lamivudine with crossover to adefovir on resistance ("adefovir salvage"), (5) entecavir monotherapy, or (6) lamivudine with crossover to entecavir on resistance ("entecavir salvage"). The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: The "do nothing" strategy was least effective yet least expensive. Compared with "do nothing," using adefovir cost an incremental $19,731. Entecavir was more effective yet more expensive than adefovir, and cost an incremental $25,626 per QALY gained versus adefovir. Selecting between entecavir versus adefovir was highly dependent on the third-party payer's "willingess-to-pay" (e.g., 45% and 60% of patients fall within budget if willing-to-pay $10K and $50K per QALY gained for entecavir, respectively). Both lamivudine monotherapy and the "salvage" strategies were not cost-effective. However, between the two salvage strategies, "adefovir salvage" was more effective and less expensive than "entecavir salvage." CONCLUSION: Both entecavir and adefovir are cost-effective in patients with HBV cirrhosis. Choosing between adefovir and entecavir is highly dependent on available budgets. In patients with HBV cirrhosis with previous lamivudine resistance, "adefovir salvage" appears more effective and less expensive than "entecavir salvage." C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,Div Gastroenterol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Digest Dis, David Geffen Sch Med, Los Angeles, CA 90073 USA. CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Mt Sinai Sch Med, New York, NY USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,Div Gastroenterol, 11301 Wilshire Blvd,Bldg 115,Room 215E, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [2P30 DK 041301-17] NR 109 TC 55 Z9 58 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 BP 2076 EP 2089 DI 10.1111/j.1572-0241.2006.00769.x PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080ZM UT WOS:000240287000022 PM 16968510 ER PT J AU Bressler, BL Korzenik, JR Sands, BE AF Bressler, Brian L. Korzenik, Joshua R. Sands, Bruce E. TI A recursive partitioning based clinical prediction rule for long term response to infliximab in patients with Crohn's disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 1110 BP S435 EP S435 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656102111 ER PT J AU Pimentel, M Chatterjee, S Chang, C Low, K Song, YL Liu, CX Lezcano, S Conklin, J Finegold, S AF Pimentel, Mark Chatterjee, Sownya Chang, Christopher Low, Kimberly Song, Yuli Liu, Chengxu Lezcano, Sheila Conklin, Jeffery Finegold, Sydney CA GI Motility Program TI Gastrointestinal infection with Campylobacter jejuni 81-176 produces altered bowel function and bacterial overgrowth in rats SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 Cedars Sinai Med Ctr, GI Motil Program, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Geffen Sch Med, Div Gastroenterol, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90073 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 1216 BP S472 EP S472 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656102217 ER PT J AU Sands, B Hass, S White, J Miller, D AF Sands, B. Hass, S. White, J. Miller, D. TI The impact of Crohn's disease on workforce participation and productivity in the workplace and household SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 1137 BP S444 EP S444 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656102138 ER PT J AU Siegel, CA Levy, C Mackenzie, TA Sands, BE AF Siegel, Corey A. Levy, Campbell Mackenzie, Todd A. Sands, Bruce E. TI Patient perceptions of the risks and benefits of infliximab for the treatment of inflammatory bowel disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 Dartmouth Hitchcock Med Ctr, Gastroenterol Sect, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 1120 BP S438 EP S438 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656102121 ER PT J AU Singal, AK Rosman, AS Post, JB Bauman, WA Korsten, MA AF Singal, Ashwani K. Rosman, Alan S. Post, James B. Bauman, William A. Korsten, Mark A. TI Effect of colonoscopy preparation on renal function: A retrospective comparison of oral sodium phosphate versus polyethylene glycol SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 James J Peters VA Med Ctr, Spinal Cord Ctr Excellence, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 512 BP S216 EP S217 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656101006 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Geographic and temporal variations in the mortality from Crohn's disease and ulcerative colitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 P3 GI, Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 1072 BP S421 EP S421 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656102073 ER PT J AU Stoffel, EM Mercado, R Ford, B Kohlmann, W Conrad, P Blanco, A Shannon, K Terdiman, J Gruber, S Chung, D Syngal, S AF Stoffel, Elena M. Mercado, Rowena Ford, Beth Kohlmann, Wendy Conrad, Peggy Blanco, Amie Shannon, Kristen Terdiman, Jonathan Gruber, Stephen Chung, Daniel Syngal, Sapna TI Low prevalence of prophylactic surgery among individuals with hereditary nonpolyposis colorectal cancer (HNPCC) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 1454 BP S553 EP S553 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656102455 ER PT J AU Webb, A Poy, I Patel, R Ali, O Page, R Kashi, M Herrera, A Schoolfield, J Brock, P Hoyumpa, A AF Webb, Amy Poy, Isela Patel, Rikin Ali, Olga Page, Robert Kashi, Maryam Herrera, Ana Schoolfield, John Brock, Paul Hoyumpa, Anastacio TI Comparison of ribavirin with PEG-interferon alpha-2a or with alpha-2b in treatment-naive patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-College-of-Gasroenterology CY OCT 20-25, 2006 CL Las Vegas, NV SP Amer Coll Gastroenterol C1 UT Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Healthcare Syst, Hepatol Clin, San Antonio, TX 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2006 VL 101 IS 9 SU S MA 412 BP S181 EP S182 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 086EH UT WOS:000240656100413 ER PT J AU Strom, JA Carabello, BA AF Strom, Joel A. Carabello, Blase A. TI Evaluation and treatment of valvular heart disease in the elderly SO AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Editorial Material C1 Univ S Florida, Dept Internal Med, Tampa, FL 33612 USA. Univ S Florida, Dept Chem Biomed Engn, Tampa, FL USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Strom, JA (reprint author), Univ S Florida, Dept Chem Engn, 4202 E Fowler Ave,ENB-118, Tampa, FL 33620 USA. EM jstrom@health.usf.edu NR 11 TC 0 Z9 0 U1 0 U2 3 PU LE JACQ LTD PI DARIEN PA 3 PARKLANDS DRIVE, DARIEN, CT 06820 USA SN 1076-7460 J9 AM J GERIATR CARDIOL JI Am. J. Geriatr. Cardiol. PD SEP-OCT PY 2006 VL 15 IS 5 BP 275 EP 276 DI 10.1111/j.1076-7460.2006.04882.x PG 2 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA 079ZN UT WOS:000240216500002 ER PT J AU Strom, JA VanAuker, MD Carabello, BA AF Strom, Joel A. VanAuker, Michael D. Carabello, Blase A. TI Effects of aging on the diagnostic assessment of valvular heart disease SO AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Review ID GRADIENT AORTIC-STENOSIS; REGURGITANT ORIFICE AREA; MITRAL REGURGITATION; PRESSURE RECOVERY; VALVE STENOSIS; SYSTEMIC HYPERTENSION; ECHOCARDIOGRAPHY; DOBUTAMINE; QUANTIFICATION; RESISTANCE AB The diagnostic assessment of the severity of valvular heart disease in the older population is impacted by the anatomic and physiologic changes that accompany normal aging and by the interposition of diseases prevalent in the elderly. In this paper, the impact of those changes on the assessment of valvular heart disease will be reviewed. Special attention will be paid to the effects of age and disease on the measurement of the pressure drop and orifice area. C1 Univ S Florida, Dept Internal Med, Tampa, FL 33612 USA. Univ S Florida, Dept Chem Biomed Engn, Tampa, FL USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Strom, JA (reprint author), Univ S Florida, Dept Chem Engn, 4202 E Fowler Ave,ENG-118, Tampa, FL 33620 USA. EM jstrom@health.usf.edu NR 39 TC 1 Z9 1 U1 0 U2 0 PU LE JACQ LTD PI DARIEN PA 3 PARKLANDS DRIVE, DARIEN, CT 06820 USA SN 1076-7460 J9 AM J GERIATR CARDIOL JI Am. J. Geriatr. Cardiol. PD SEP-OCT PY 2006 VL 15 IS 5 BP 286 EP 290 DI 10.1111/j.1076-7460.2006.04624.x PG 5 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA 079ZN UT WOS:000240216500004 PM 16957447 ER PT J AU Garshick, E Laden, F Hart, JE Smith, TJ Rosner, B AF Garshick, Eric Laden, Francine Hart, Jaime E. Smith, Thomas J. Rosner, Bernard TI Smoking imputation and lung cancer in railroad workers exposed to diesel exhaust SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE diesel exhaust; lung cancer; multiple imputation; smoking ID MULTIPLE IMPUTATION; RETROSPECTIVE COHORT; HEALTH; PREVALENCE; EXPOSURES; MORTALITY; VALIDITY AB Background: An association between diesel exhaust exposure and lung cancer mortality in a large retrospective cohort study of US railroad workers has previously been reported. However, specific information regarding cigarette smoking was unavailable. Methods: Birth cohort, age, job, and cause of death specific smoking histories from a companion case-control study were used to impute smoking behavior for 39,388 railroad workers who died 1959-1996. Mortality analyses incorporated the effect of smoking on lung cancer risk. Results: The smoking adjusted relative risk of lung cancer in railroad workers exposed to diesel exhaust compared to unexposed workers was 1.22 (95% CI = 1.12-1.32), and unadjusted for smoking the relative risk was 1.35 (95% CI = 1.24-1.46). Conclusions: These analyses illustrate the use of imputation in record-based occupational health studies to assess potential confounding due to smoking. In this cohort, small differences in smoking behavior between diesel exposed and unexposed workers did not explain the elevated lung cancer risk. C1 VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, W Roxbury, MA 02132 USA. Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM eric.garshick@med.va.gov FU NCI NIH HHS [R01 CA079725, CA79725]; PHS HHS [CCR115818] NR 32 TC 21 Z9 22 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD SEP PY 2006 VL 49 IS 9 BP 709 EP 718 DI 10.1002/ajim.20344 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 075DD UT WOS:000239862100001 PM 16767725 ER PT J AU Saint, S Kaufman, SR Rogers, MAM Baker, PD Boyko, EJ Lipsky, BA AF Saint, Sanjay Kaufman, Samuel R. Rogers, Mary A. M. Baker, Paul D. Boyko, Edward J. Lipsky, Benjamin A. TI Risk factors for nosocomial urinary tract-related bacteremia: A case-control study SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID BLOOD-STREAM INFECTION; 4-YEAR PROSPECTIVE EVALUATION; CATHETER-RELATED BACTERIURIA; CRITICALLY-ILL PATIENTS; PATIENT SAFETY; EPIDEMIOLOGY; MICROBIOLOGY; SMOKING; BLADDER; HOSPITALS AB Background: Risk factors for bacteremia in patients with hospital-acquired bacteriuria are largely unknown. Given the morbidity and costs associated with nosocomial bacteremia, determining risk factors could enhance the safety of hospitalized patients. Methods: We conducted a case-control study within the Veterans Affairs Puget Sound Health Care System. A patient hospitalized between 1984 and 1999 from whom a urine culture and a blood culture grew the same organism >= 48 hours after admission was considered a case. Control patients were those with significant bacteriuria detected 48 hours after admission who did not have a positive blood culture. We used logistic regression to determine independent risk factors for bacteremia. Results: There were 95 cases and 142 controls. Independent, statistically significant predictors of bacteremia included immunosuppressant therapy within 14 days of bacteriuria (odds ratio [OR], 8.13); history of malignancy (OR, 1.94); male sex (OR, 1.88); cigarette use in the past 5 years (OR, 1.26); number of hospital days before bacteriuria (OR, 1.03); and antibiotic use within 3 days of bacteriuria (OR, 0.76). corticosteroid use within 7 days of bacteriuria predicted bacteremia in patients < 70 years old (OR, 14.24). Similarly, patients < 70 years old were more likely to develop bacteremia if they had diabetes mellitus (OR, 6.19). Conclusion: Delineating risk factors for nosocomial urinary tract-related bacteremia can help target appropriate preventive practices at the highest risk patients. C1 Ann Arbor VA Hlth Serv Res & Dev Ctr Excellence, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Div Gen Med, Ann Arbor, MI 48109 USA. UM Patient Safety Enhancement Program, Ann Arbor, MI USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Saint, S (reprint author), Room 7E08,300 NIB,Campus Box 0429, Ann Arbor, MI 48109 USA. EM saint@umich.edu RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 FU AHRQ HHS [P20-HS11540] NR 39 TC 27 Z9 29 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD SEP PY 2006 VL 34 IS 7 BP 401 EP 407 DI 10.1016/j.ajic.2006.03.001 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 083HM UT WOS:000240447000001 PM 16945684 ER PT J AU Wiederkehr, MR Nicosia, RF Munschauer, C Moe, OW AF Wiederkehr, Michael R. Nicosia, Roberto F. Munschauer, Cary Moe, Orson W. TI An unusual case of urticaria and nephrotic syndrome SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE urticarial vasculitis; hypocomplementemia; nephrotic syndrome; membranous glomerulonephritis; mycophenolate mofetil; anti-C1q antibodies; angiodedema ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; VASCULITIS-SYNDROME; DISEASE; C1Q; AUTOANTIBODIES; ASSOCIATION; DEFICIENCY; NEPHRITIS; ARTHRITIS C1 Baylor Univ, Med Ctr, Dallas Nephrol Associates, Div Nephrol, Dallas, TX 75246 USA. Baylor Univ, Med Ctr, Div Vasc Surg, Dallas, TX 75246 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Seattle, WA USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Wiederkehr, MR (reprint author), Baylor Univ, Med Ctr, Dallas Nephrol Associates, Div Nephrol, 3500 Gaston Ave, Dallas, TX 75246 USA. EM wiederkehrm@dneph.com NR 21 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2006 VL 48 IS 3 BP 506 EP 512 DI 10.1053/j.ajkd.2006.03.087 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 084WY UT WOS:000240566300020 PM 16931227 ER PT J AU Levy, DE AF Levy, Douglas E. TI Employer-sponsored insurance coverage of smoking cessation treatments SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID SUSTAINED-RELEASE BUPROPION; COST-EFFECTIVENESS; DIFFERENT COMBINATIONS; BEHAVIORAL TREATMENT; CONTROLLED-TRIAL; NICOTINE PATCH; HEALTH; PERSPECTIVE; SERVICES; IMPACT AB Objective: To investigate the costs and benefits of covering smoking cessation interventions from insurers' and employers' perspectives. Study Design: A Monte Carlo model was used to simulate smoking status and health expenditures in a hypothetical population of employees over a period of 20 years. Methods: Population characteristics were drawn from the 19972002 National Health Interview surveys. Multivariate regressions using a number of publicly available datasets from 1996-2002 generated transition probabilities for the simulation. The costs and benefits of scenarios where smoking cessation treatments were covered were compared with a scenario where none were covered. Sensitivity to parameter estimates was evaluated. Results: By the final simulation year, insurers had benefit-cost ratios of 0.56 to 1.67 with per member per month costs of -$0.22 to $0.43. The earliest year at which savings were achieved for insurers was year 8. Employers saw benefit-cost ratios of 1.88 to 5.58 by the final simulation year with per member per month costs of -$1.23 to -$0.15. Employers achieved savings as early as year 3 and as late as year 8. Models were sensitive to the rate at which population members were assumed to exit the insurer or employer. Conclusion: Both insurers and employers may add smoking cessation benefits at minimal burden to their members and with potential savings, particularly where the population of interest is relatively stable. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Levy, DE (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM douglas_levy@post.harvard.edu FU AHRQ HHS [T32 HS 000020]; NIA NIH HHS [T32 AG 00186] NR 36 TC 9 Z9 9 U1 4 U2 7 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2006 VL 12 IS 9 BP 553 EP 562 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 084ZL UT WOS:000240572800006 PM 16961444 ER PT J AU Lieberman, D AF Lieberman, David TI Screening for colorectal cancer in average-risk populations SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE colorectal cancer; colonoscopy; fecal occult blood test; sigmoidoscopy; computed tomographic; colonography ID FECAL-OCCULT-BLOOD; COMPUTED TOMOGRAPHIC COLONOGRAPHY; CONTRAST BARIUM ENEMA; ASYMPTOMATIC ADULTS; FLEXIBLE SIGMOIDOSCOPY; VIRTUAL COLONOSCOPY; NATIONAL-SURVEY; TASK-FORCE; RECOMMENDATIONS; MORTALITY AB Screening average-risk populations for colorectal cancer can reduce the incidence and mortality of colorectal cancer. Effectiveness depends on programmatic adherence and quality. This review discusses the evidence supporting the use of currently available screening tests. The discussion specifically focuses on programmatic issues and highlights the importance of quality assurance in each program. (c) 2006 Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97239 USA. RP Lieberman, D (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol, P3-GI,POB 1034, Portland, OR 97239 USA. EM lieberma@ohsu.edu NR 47 TC 17 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2006 VL 119 IS 9 BP 728 EP 735 DI 10.1016/j.amjmed.2006.03.037 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 079TC UT WOS:000240199800004 PM 16945604 ER PT J AU Gregory, SA Akutsu, Y Perlstein, TS Yasuda, T Yurchak, PM AF Gregory, Shawn A. Akutsu, Yasushi Perlstein, Todd S. Yasuda, Tsunehiro Yurchak, Peter M. TI Inverted U waves SO AMERICAN JOURNAL OF MEDICINE LA English DT Article C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Dis,Dept Med, Boston, MA 02115 USA. RP Gregory, SA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Ctr, Dept Med, Suite 5800,55 Fruit St, Boston, MA 02114 USA. EM sagregory@partners.org FU NHLBI NIH HHS [5K30HL004095-06]; NIBIB NIH HHS [1T32EB001632-01] NR 2 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2006 VL 119 IS 9 BP 746 EP 747 DI 10.1016/j.amjmed.2006.07.017 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 079TC UT WOS:000240199800008 PM 16945608 ER PT J AU Bosworth, HB Rockey, DC Paulson, EK Niedzwiecki, D Davis, W Sanders, LL Yee, J Henderson, J Hatten, P Burdick, S Sanyal, A Rubin, DT Sterling, M Akerkar, G Bhutani, MS Binmoeller, K Garvie, J Bini, EJ McQuaid, K Foster, WL Thompson, WM Dachman, A Halvorsen, R AF Bosworth, Hayden B. Rockey, Don C. Paulson, Erik K. Niedzwiecki, Donna Davis, Wendy Sanders, Linda L. Yee, Judy Henderson, Jim Hatten, Paul Burdick, Steve Sanyal, Arun Rubin, David T. Sterling, Mark Akerkar, Geetanjali Bhutani, Manoop S. Binmoeller, Kenneth Garvie, John Bini, Edmund J. McQuaid, Kenneth Foster, William L. Thompson, William M. Dachman, Abe Halvorsen, Robert TI Prospective comparison of patient experience with colon imaging tests SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE air contrast barium enema; virtual colonoscopy; computed tomography; computed tomographic; colonography; colonoscopy; cancer screening; patient preference; colon cancer; satisfaction ID CONTRAST BARIUM ENEMA; COMPUTED TOMOGRAPHIC COLONOGRAPHY; CT COLONOGRAPHY; VIRTUAL COLONOSCOPY; COLORECTAL-CANCER; CONVENTIONAL COLONOSCOPY; PERFORMANCE; PREFERENCES; NEOPLASIA; POLYPS AB PURPOSE: Patient experience varies with the currently available colon imaging tests, including air contrast barium enema, computed tomographic colonography, and colonoscopy. We examined differences in patient experience with colon imaging tests and whether they varied with gender, age, and race. SUBJECTS AND METHODS: Patients with fecal occult blood, hematochezia, iron-deficiency anemia, or a family history of colon cancer underwent air contrast barium enema followed 7 to 14 days later by computed tomographic colonography and colonoscopy. Validated patient experience questionnaires that measured the experience for each test and a separate questionnaire that obtained an overall summary measure were administered after testing. Eleven patient experiences including pain, embarrassment, difficulty with bowel preparation, and satisfaction with tests were examined. RESULTS: A total of 614 subjects completed all 3 imaging tests. The test most patients were willing to repeat was colonoscopy; it also was reported to be the least painful procedure. Patients were least satisfied with air contrast barium enema, and fewer would undergo air contrast barium enema compared with computed tomographic colonography or colonoscopy. There were limited racial and gender differences in perceptions of the tests. Younger adults perceived air contrast barium enema to be more painful than older adults. CONCLUSION: Taking into account a wide variety of patient experience measures, patients preferred colonoscopy to air contrast barium enema and computed tomographic colonography. This finding has important implications for physicians considering different colon imaging tests. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Div Digest & Liver Dis, Dallas, TX 75390 USA. Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA. Duke Univ, Med Ctr, Durham VA Med Ctr, Durham, NC 27706 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Troy Internal Med, Troy, MI USA. Indian River Radiol, Vero Beach, FL USA. Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. Univ Chicago, Chicago, IL 60637 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Seacoast Gastroenterol, Exeter, NH USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Calif Pacific Med Ctr, San Francisco, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. NYU, New York, NY USA. RP Rockey, DC (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Div Digest & Liver Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM don.rockey@utsouthwestern.edu FU NCI NIH HHS [R01 CA82344] NR 24 TC 55 Z9 57 U1 0 U2 2 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2006 VL 119 IS 9 BP 791 EP 799 DI 10.1016/j.amjmed.2006.02.013 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 079TC UT WOS:000240199800015 PM 16945615 ER PT J AU Iordanova, B Rosenbaum, D Norman, D Weiner, M Studholme, C AF Iordanova, B. Rosenbaum, D. Norman, D. Weiner, M. Studholme, C. TI MR imaging anatomy in neurodegeneration: A robust volumetric parcellation method of the frontal lobe gyri with quantitative validation in patients with dementia SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID VOXEL-BASED MORPHOMETRY; PREFRONTAL CORTEX; SEGMENTATION METHOD; HUMAN BRAIN; SCHIZOPHRENIA; CINGULATE; SULCI AB BACKGROUND AND PURPOSE: Brain volumetry is widely used for evaluating tissue degeneration; however, the parcellation methods are rarely validated and use arbitrary planes to mark boundaries of brain regions. The goal of this study was to develop, validate, and apply an MR imaging tracing method for the parcellation of 3 major gyri of the frontal lobe, which uses only local landmarks intrinsic to the structures of interest, without the need for global reorientation or the use of dividing planes or lines. METHODS: Studies were performed on 25 subjects- healthy controls and subjects diagnosed with Lewy body dementia and Alzheimer disease-with significant variation in the underlying gyral anatomy and state of atrophy. The protocol was evaluated by using multiple observers tracing scans of subjects diagnosed with neurodegenerative disease and those aging normally, and the results were compared by spatial overlap agreement. To confirm the results, observers marked the same locations in different brains. We illustrated the variabilities of the key boundaries that pose the greatest challenge to defining consistent parcellations across subjects. RESULTS: The resulting gyral volumes were evaluated, and their consistency across raters was used as an additional assessment of the validity of our marking method. The agreement on a scale of 0-1 was found to be 0.83 spatial and 0.90 volumetric for the same rater and 0.85 spatial and 0.90 volumetric for 2 different raters. The results revealed that the protocol remained consistent across different neurodegenerative conditions. CONCLUSION: Our method provides a simple and reliable way for the volumetric evaluation of frontal lobe neurodegeneration and can be used as a resource for larger comparative studies as well as a validation procedure of automated algorithms. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Dept Radiol, Magnet Resonance Unit, San Francisco, CA USA. RP Iordanova, B (reprint author), Carnegie Mellon Univ, Mellon Inst 601, 4400 5th Av, Pittsburgh, PA 15213 USA. EM biordano@andrew.cmu.edu FU NIA NIH HHS [P01 AG012435, R01 AG10897, P01 AG19724, P01 AG019724, P01 AG12435, R01 AG010897]; NIAAA NIH HHS [P01 AA011493, P01 AA11493]; NIBIB NIH HHS [R01 EB00822, R01 EB000822]; NIMH NIH HHS [R01 MH065392, R01 MH65392] NR 27 TC 4 Z9 4 U1 1 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2006 VL 27 IS 8 BP 1747 EP 1754 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 086AJ UT WOS:000240645200039 PM 16971629 ER PT J AU De Freitas, D Martins, EN Adan, C Alvarenga, LS Pavan-Langston, D AF De Freitas, Denise Martins, Elisabeth N. Adan, Consuelo Alvarenga, Lenio S. Pavan-Langston, Deborah TI Herpes zoster ophthalmicus in otherwise healthy children SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ORAL ACYCLOVIR; POSTHERPETIC NEURALGIA; INTRAUTERINE EXPOSURE; VARICELLA VACCINE; ANTIVIRAL THERAPY; VIRUS-INFECTIONS; NATURAL-HISTORY; SIMPLEX VIRUS; INFANCY AB center dot PURPOSE: To evaluate the complications of herpes zoster ophthalmicus (HZO) in children. center dot DESIGN: Prospective-observational case series. center dot METHODS: Ten healthy patients (five boys, five girls) with HZO were prospectively followed. Data regarding best-corrected visual acuity, biomicroscopy, intraocular pressure, corneal sensitivity, and funduscopy were collected. The median duration of follow-up was 19 months (range eight to 78 months). center dot RESULTS: The mean age at presentation was 8.7 years (range two to 14 years +/- 3.95). At last visit, two patients (20%) had decreased visual acuity and nine (90%) had some degree of abnormal corneal sensitivity and corneal opacity despite good final visual acuity. center dot CONCLUSION: In general, HZO seems to have a good prognosis in healthy children; nonetheless, some cases can present severe eye complications causing visual loss. C1 Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Martins, EN (reprint author), Rua Itapeva 518 Cj 1208, BR-01332000 Sao Paulo, Brazil. EM beth@oftalmo.epm.br NR 67 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2006 VL 142 IS 3 BP 393 EP 399 DI 10.1016/j.ajo.2006.03.059 PG 7 WC Ophthalmology SC Ophthalmology GA 082MJ UT WOS:000240390600004 PM 16935582 ER PT J AU Adamian, M Pawlyk, BS Hong, DH Berson, EL AF Adamian, Michael Pawlyk, Basil S. Hong, Dong-Hyun Berson, Eliot L. TI Rod and cone opsin mislocalization in an autopsy eye from a carrier of X-linked retinitis pigmentosa with a Gly436Asp mutation in the RPGR gene SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RP2 AB PURPOSE: We investigated whether opsin mislocalization occurs in photoreceptors in a female carrier of X-linked retinitis pigmentosa with a Gly436Asp mutation in the retinitis pigmentosa GTPase regulator gene (RPGR). DESIGN: Histologic findings in autopsy eyes from a carrier were compared with those from a normal female. METHODS: Frozen retinal sections from the periphery of one eye of the carrier and the normal were stained with antibodies against either human red or green opsins, blue cone opsin, or rhodopsin and labeled with fluorochrome conjugated secondary antibodies. Cell nuclei were counterstained with Hoechst dye. Fellow eyes were evaluated with light microscopy. RESULTS: Fluorescent labeling showed mislocalized cone and rod opsins in photoreceptor cells only in the carrier. The carrier also showed some loss of photoreceptor nuclei. CONCLUSIONS: A defect in trafficking of opsins to outer segments exists in a carrier with the RPGR Gly436Asp mutation. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Boston, MA 02114 USA. Texas Q&M Univ, Dept Vet Pathobiol, College Stn, TX USA. RP Berson, EL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169] NR 5 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2006 VL 142 IS 3 BP 515 EP 518 DI 10.1016/j.ajo.2006.03.061 PG 4 WC Ophthalmology SC Ophthalmology GA 082MJ UT WOS:000240390600033 PM 16935610 ER PT J AU Kawai, T Matsuyama, T Hosokawa, Y Makihira, S Seki, M Karimbux, NY Goncalves, RB Valverde, P Dibart, S Li, YP Miranda, LA Ernst, CWO Izumi, Y Taubman, MA AF Kawai, Toshihisa Matsuyama, Takashi Hosokawa, Yoshitaka Makihira, Seicho Seki, Makoto Karimbux, Nadeem Y. Goncalves, Reginaldo B. Valverde, Paloma Dibart, Serge Li, Yi-Ping Miranda, Leticia A. Ernst, Cory W. O. Izumi, Yuichi Taubman, Martin A. TI B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID OSTEOCLASTOGENESIS INHIBITORY FACTOR; GINGIVAL CREVICULAR FLUID; OSTEOPROTEGERIN LIGAND; CELLS; DIFFERENTIATION; EXPRESSION; OSTEOPOROSIS; ANTIBODIES; TISSUES; ACTIVATION AB Receptor activator of nuclear factor-kappa B (RANKL)-mediated osteoclastogenesis plays a pivotal role in inflammatory bone resorption. The aim of this study was to identify the cellular source of RANKL in the bone resorptive lesions of periodontal disease. The concentrations of soluble RANKL, but not its decoy receptor osteoprotegerin, measured in diseased tissue homogenates; were significantly higher in diseased gingival tissues than in healthy tissues. Double-color confocal microscopic analyses demonstrated less than 20% of both B cells and T cells expressing RANKL in healthy gingival tissues. By contrast, in the abundant mononuclear cells composed of 45% T cells, 50% B cells, and 5% monocytes in diseased gingival tissues, more than 50 and 90% of T cells and B cells, respectively, expressed RANKL. RANKL production by nonlymphoid cells was not distinctly identified. Lymphocytes isolated from gingival tissues of patients induced differentiation of mature osteoclast cells in a RANKL-dependent manner in vitro. However, similarly isolated peripheral blood B and T cells did not induce osteoclast differentiation, unless they were activated in vitro to express RANKL; emphasizing the osteoclastogenic potential of activated RANKL-expressing lymphocytes in periodontal disease tissue. These results suggest that activated T and B cells can be the cellular source of RANKL for bone resorption in periodontal diseased gingival tissue. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Tufts Univ, Sch Dent Med, Dept Gen Dent, Boston, MA 02111 USA. Boston Univ, Goldman Sch Grad Dent, Dept Periodontol, Boston, MA 02215 USA. Kagoshima Univ, Dept Periodontol, Kagoshima 890, Japan. Mitsubishi Pharma, R&D Div, Tokyo, Japan. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 The Fenway, Boston, MA 02115 USA. EM mtaubman@forsyth.org RI Valverde, Paloma/A-9897-2008 FU NIDCR NIH HHS [DE-03420, DE-14551, DE-15722, K22 DE014551, R01 DE003420, R03 DE015722, R37 DE003420] NR 59 TC 228 Z9 234 U1 0 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2006 VL 169 IS 3 BP 987 EP 998 DI 10.2353/ajpath.2006.060180 PG 12 WC Pathology SC Pathology GA 077RY UT WOS:000240048900024 PM 16936272 ER PT J AU Paintlia, AS Paintlia, MK Singh, I Singh, AK AF Paintlia, Ajaib S. Paintlia, Manjeet K. Singh, Inderjit Singh, Avtar K. TI Immunomodulatory effect of combination therapy with lovastatin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside alleviates neurodegeneration in experimental autoimmune encephalomyelitis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; COA REDUCTASE INHIBITOR; REMITTING MULTIPLE-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; GLATIRAMER ACETATE; ENDOTHELIAL-CELLS; CONTROLLED-TRIAL; PROGRESSIVE MS; TH2 BIAS; EXPRESSION AB Combination therapy with multiple sclerosis (MS) therapeutics is gaining momentum over monotherapy for improving MS. Lovastatin, an HMG-CoA reductase inhibitor (statin), was immunomodulatory in an experimental autoimmune encephalomyelitis (EAE) model of MS. Lovastatin biases the immune response from Th1 to a protective Th2 response in EAE by a different mechanism than 5-aminoimidazole-4-carboxaniide-1-13-D-ribofuranoside, an immunomodulating agent that activates AMP-activated protein kinase. Here we tested these agents in combination in an EAE model of MS. Suboptimal doses of these drugs in combination were additive in efficacy against the induction of EAE; clinical symptoms were delayed and severity and duration of disease was reduced. in the central nervous system, the cellular infiltration and proinflammatory immune response was decreased while the anti-inflammatory immune response was increased. Combination treatment biased the class of elicited myelin basic protein antibodies from IgG2a to IgG1 and IgG2b, suggesting a shift from Th1 to Th2 response. In addition, combination therapy lessened inflammation-associated neurodegeneration in the central nervous system of EAE animals. These effects were absent in EAE animals treated with either drug alone at the same dose. Thus, our data suggest that agents with different mechanisms of action such as lovastatin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofruranoside, when used in combination, could improve therapy for central nervous system de-myelinating diseases and provide a rationale for testing them in MS patients. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NCRR NIH HHS [C06 RR018823, C06 RR015455, C06-RR015455, C06-RR018823]; NIA NIH HHS [AG-025307, R56 AG025307]; NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144, NS-40810, R01 NS022576, R01 NS034741, R01 NS037766, R01 NS040144, R01 NS040810, R37 NS022576] NR 52 TC 24 Z9 30 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2006 VL 169 IS 3 BP 1012 EP 1025 DI 10.2353/ajpath.2006.051309 PG 14 WC Pathology SC Pathology GA 077RY UT WOS:000240048900026 PM 16936274 ER PT J AU Weaver, FM Smith, B Evans, CT Kurichi, JE Patel, N Kapur, VK Burns, SP AF Weaver, F. M. Smith, B. Evans, C. T. Kurichi, J. E. Patel, N. Kapur, V. K. Burns, S. P. TI Outcomes of outpatient visits for acute respiratory illness in veterans with spinal cord injuries and disorders SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE respiratory care; infection; outcomes; spinal cord injuries; veterans ID COMMUNITY-ACQUIRED PNEUMONIA; MORTALITY; HOSPITALIZATION; DEATH; RISK; POPULATION; INFECTION; ETIOLOGY; TRENDS; IMPACT AB Objective: Respiratory complications are a leading cause of death in persons with spinal cord injuries and disorders (SCI&D). We examined same-day and 60-day hospitalizations and 60-day mortality after acute respiratory illness (ARI) outpatient visits. Design: A longitudinal study was conducted of 8775 ARI visits in the Veterans Health Administration (VA) (October. 1997-September 2002) by persons with SCI&D. ARIs included upper respiratory infections (URI), acute bronchitis, pneumonia, and influenza (P&I). Results: URIs accounted for almost half of all (49%) visits. A total of 14.9% of patients with ARIs were hospitalized the same day; 30.8% were hospitalized within 60 days. Predictors of hospitalization included diagnosis of either P&I or acute bronchitis, comorbid illness, level of injury, age, and VA SCI center visit. Overall 60-day mortality was 2.9% but was 7.9% for pneumonia. Mortality was related to diagnosis (P&I: odds ratio [OR] = 9.80, 95% confidence interval [CI]: 6.27-13.33; acute bronchitis: OR = 2.00, 95% CI: 1.08 -2.93), age (65+: OR = 3.96, 95%, CI: 2.23-5.70), and comorbid conditions (OR = 1.94, 95% Cl: 1.432.46). Conclusions: P&I and acute bronchitis were associated with increased VA hospitalization and mortality rates. The case fatality rate for pneumonia is higher for SCI&D than the general population. Level of injury predicted hospitalization but not death. Efforts to improve prevention and treatment of ARIs in persons with SCI&D are needed. C1 Hines VA Hosp, Midw Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Hines VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. Northwestern Univ, Inst Heathcare Studies, Chicago, IL 60611 USA. Univ Penn, Sch Med, Dept Rehabil Med, Philadelphia, PA 19104 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Div Pulm & Crit Care Med, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Harborview Injury Prevent & Res Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, SCI Serv, Seattle, WA USA. RP Weaver, FM (reprint author), Hines VA Hosp, Midw Ctr Hlth Serv & Policy Res, HSR&D,151H,Bldg 1,Room B260,5th & Roosevelt Rd, Hines, IL 60141 USA. RI Kapur, Vishesh/K-1054-2014 OI Kapur, Vishesh/0000-0002-5417-1097 NR 29 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP PY 2006 VL 85 IS 9 BP 718 EP 726 DI 10.1097/01.phm.0000223403.94148.67 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 077PV UT WOS:000240043000003 PM 16924184 ER PT J AU Yu, HY Hirshman, MF Fujii, N Pomerleau, JM Peter, LE Goodyear, LJ AF Yu, Haiyan Hirshman, Michael F. Fujii, Nobuharu Pomerleau, Jason M. Peter, Lauren E. Goodyear, Laurie J. TI Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase gamma 3-subunit differentially regulates glycogen accumulation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article ID PARKINSON-WHITE-SYNDROME; DOMINANT RETINITIS-PIGMENTOSA; GAMMA-SUBUNIT ISOFORMS; SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; CHLORIDE CHANNEL; FOOD-INTAKE; HYPERTROPHIC CARDIOMYOPATHY; VENTRICULAR PREEXCITATION; CARDIAC-HYPERTROPHY AB AMP-activated protein kinase ( AMPK) is a heterotrimeric complex that works as an energy sensor to integrate nutritional and hormonal signals. The naturally occurring R225Q mutation in the gamma 3-subunit in pigs is associated with abnormally high glycogen content in skeletal muscle. Becauses skeletal muscle accounts for most of the body's glucose uptake, and gamma 3 is specifically expressed in skeletal muscle, it is important to understand the underlying mechanism of this mutation in regulating glucose and glycogen metabolism. Using skeletal muscle-specific transgenic mice overexpressing wild type mu 3 (WT mu 3) and R225Q mutant mu 3 (MUT gamma 3), we show that both WT gamma 3 and MUT gamma 3 mice have 1.5- to 2-fold increases in muscle glycogen content. In WT gamma 3 mice, increased glycogen content was associated with elevated total glycogen synthase activity and reduced glycogen phosphorylase activity, whereas alterations in activities of these enzymes could not explain elevated glycogen in MUT gamma 3 mice. Basal, 5-aminoimidazole-AICAR- and phenformin-stimulated AMPK alpha 2 isoform-specific activities were decreased only in MUT gamma 3 mice. Basal rates of 2-DG glucose uptake were decreased in both WT gamma 3 and MUT gamma 3 mice. However, AICAR- and phenformin-stimulated 2-DG glucose uptake were blunted only in MUT gamma 3 mice. In conclusion, expression of either wild type or mutant gamma 3-subunit of AMPK results in increased glycogen concentrations in muscle, but the mechanisms underlying this alteration appear to be different. Furthermore, mutation of the gamma 3-subunit is associated with decreases in AMPK alpha 2 isoform-specific activity and impairment in AICAR- and phenformin-stimulated skeletal muscle glucose uptake. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Laurie.Goodyear@Joslin.Harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR-42338, AR-45670]; NIDDK NIH HHS [DK-36836] NR 56 TC 16 Z9 16 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2006 VL 291 IS 3 BP E557 EP E565 DI 10.1152/ajpendo.00073.2006 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 074CN UT WOS:000239790200017 PM 16638825 ER PT J AU Satoh, A Gukovskaya, AS Reeve, JR Shimosegawa, T Pandol, SJ AF Satoh, Akihiko Gukovskaya, Anna S. Reeve, Joseph R., Jr. Shimosegawa, Tooru Pandol, Stephen J. TI Ethanol sensitizes NF-kappa B activation in pancreatic acinar cells through effects on protein kinase C-epsilon SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE alcoholic pancreatitis; cholecystokinin; inflammatory response; protein kinase C-epsilon translocation activator ID CARDIAC PROTECTION; PKC-EPSILON; CHOLECYSTOKININ; ALCOHOL; DELTA; PHOSPHORYLATION; CCK; TRANSLOCATION; PENETRATIN; INCREASES AB Although ethanol abuse is the most common cause of pancreatitis, the mechanism of alcohol's effect on the pancreas is not well understood. Previously, we demonstrated that in vitro ethanol treatment of pancreatic acinar cells augmented the CCK-8-induced activation of NF-kappa B, a key signaling system involved in the inflammatory response of pancreatitis. In the present study, we determine the role for individual PKC isoforms in the sensitizing effect of ethanol on NF-kappa B activation. Dispersed rat pancreatic acini were treated with and without ethanol and then stimulated with CCK-8; 100 nM CCK-8 caused both NF-kappa B and PKC-delta, -epsilon, and -zeta activation, whereas 0.1 nM CCK-8 did not increase PKC-delta, PKC-delta, or NF-kappa B activity. CCK-8 (0.1 nM) did activate PKC-delta. PKC-epsilon activator alone did not cause NF-kappa B activation; however, together with 0.1 nM CCK-8, it caused NF-kappa B activation. Ethanol activated PKC-epsilon without affecting other PKC isoforms or NF-kappa B activity. Of note, stimulation of acini with ethanol and 0.1 nM CCK-8 resulted in the activation of PKC-epsilon, PKC-epsilon, and NF-kappa B. The NF-kappa B activation to 0.1 nM CCK-8 in ethanol-pretreated acini was inhibited by both PKC-delta inhibitor and PKC-epsilon inhibitor. Taken together, these results demonstrate the different modes of activation of PKC isoforms and NF-kappa B in acini stimulated with ethanol, high-dose CCK-8, and low-dose CCK-8, and furthermore suggest that activation of both PKC-epsilon and -delta is required for NF-kappa B activation. These results suggest that ethanol enhances the CCK-8 induced NF-kappa B activation at least in part through its effects on PKC-epsilon. C1 W LA Healthcare Ctr, VA Greater LA Healthcare Syst, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi 980, Japan. RP Pandol, SJ (reprint author), W LA Healthcare Ctr, VA Greater LA Healthcare Syst, Res Ctr Alcohol Liver & Pancreat Dis, Bldg 258,Rm 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM stephen.pandol@med.va.gov FU NIAAA NIH HHS [1 U56 AA-0114643]; NIDDK NIH HHS [R01-DK-59508]; PHS HHS [P50-A11999] NR 36 TC 38 Z9 41 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2006 VL 291 IS 3 BP G432 EP G438 DI 10.1152/ajpgi.00579.2005 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 072NH UT WOS:000239679600008 PM 16574982 ER PT J AU Janech, MG Fitzgibbon, WR Nowak, MW Miller, DH Paul, RV Ploth, DW AF Janech, Michael G. Fitzgibbon, Wayne R. Nowak, Mark W. Miller, Donald H. Paul, Richard V. Ploth, David W. TI Cloning and functional characterization of a second urea transporter from the kidney of the Atlantic stingray, Dasyatis sabina SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT Satellite Symposium of the 34th World Congress of the International-Union-of-Physiological-Sciences CY AUG 24, 2001 CL AUCKLAND COLL EDUC, AUCKLAND, NEW ZEALAND SP Int Union Physiol Sci HO AUCKLAND COLL EDUC DE elasmobranch; euryhaline; alternative splicing; osmoregulation ID AGONIST-INDUCED DESTABILIZATION; RECEPTOR MESSENGER-RNA; RAT-KIDNEY; MOLECULAR CHARACTERIZATION; MARINE ELASMOBRANCH; SQUALUS-ACANTHIAS; RAJA-ERINACEA; LOCALIZATION; UT-A3; OSMOREGULATION AB The cloning of cDNAs encoding facilitated urea transporters (UTs) from the kidneys of the elasmobranchs indicates that in these fish renal urea reabsorption occurs, at least in part, by passive processes. The previously described elasmobranch urea transporter clones from shark (shUT) and stingray (strUT-1) differ from each other primarily because of the COOH-terminus of the predicted strUT-1 translation product being extended by 51-amino acid residues compared with shUT. Previously, we noted multiple UT transcripts were present in stingray kidney. We hypothesized that a COOH terminally abbreviated UT isoform, homologous to shUT, would also be present in stingray kidney. Therefore, we used 5'/3' rapid amplification of cDNA ends to identify a 3'UTR-variant (strUT-1a) of the cDNA that encodes (strUT-1), as well as three, 3'UTR-variant cDNAs (strUT-2a, b, c) that encode a second phloretin-sensitive, urea transporter (strUT-2). The 5'UTR and the first 1,132 nucleotides of the predicted coding region of the strUT-2 cDNAs are identical to the strUT-1 cDNAs. The remainder of the coding region contains only five novel nucleotides. The strUT-2 cDNAs putatively encode a 379-amino acid protein, the first 377 amino acids identical to strUT-1 plus 2 additional amino acids. We conclude that 1) a second UT isoform is expressed in the Atlantic stingray and that this isoform is similar in size to the UT previously cloned from the kidney of the dogfish shark, and 2) at least five transcripts encoding the 2 stingray UTs are derived from a single gene product through alternative splicing and polyadenylation. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Marine Biomed & Environm Sci Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol & Expt Therapeut, Marine Biomed & Environm Sci Ctr, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Fitzgibbon, WR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Marine Biomed & Environm Sci Ctr, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM fitzgiwr@musc.edu OI Janech, Michael/0000-0002-3202-4811 NR 46 TC 14 Z9 14 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2006 VL 291 IS 3 BP R844 EP R853 DI 10.1152/ajpregu.00739.2005 PG 10 WC Physiology SC Physiology GA 072FH UT WOS:000239658800046 PM 16614049 ER PT J AU Schnoll, RA Rukstalis, M Wileyto, EP Shields, AE AF Schnoll, Robert A. Rukstalis, Margaret Wileyto, E. Paul Shields, Alexandra E. TI Smoking cessation treatment by primary care physicians - An update and call for training SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COUNSELING PRACTICES; MULTIPLE IMPUTATION; TOBACCO DEPENDENCE; UNITED-STATES; HEALTH; SMOKERS; PRACTITIONERS; INTERVENTIONS; DOCUMENTATION; DISPARITIES AB Background: Public health and government organizations have invested considerably to increase physician adherence to smoking-cessation practice guidelines. Methods: A random sample of 2000 U.S. primary care physicians was ascertained from the American Medical Association (AMA) in 2002. Respondents (n = 1120, 62.3 %) provided self-reported data about individual and practice characteristics and smoking-cessation practices. Data were analyzed in 2005. Results: Most primary care physicians (75%) advised cessation, 64% recommended nicotine patches, 67% recommended bupropion, 32% recommended nicotine gum, 10% referred to cessation experts, and 26% referred to cessation programs "often or always." Advising cessation was related to being older, having a faculty appointment, having trained staff for smoking counseling, and having confidence to counsel patients about smoking. Physicians who were internists, younger, and those with greater confidence to counsel patients about smoking recommended nicotine replacement more often. Prescribing bupropion was less common among older physicians, in the Northeast, with trained staff available for counseling, and with a greater proportion of minority or Medicaid patients. Prescribing bupropion was more common among AMA-member physicians and physicians with greater confidence to counsel patients about smoking. Providing a referral to an outside expert or program was more common among female physicians, and physicians in the Northeast or West, with larger clinical practices, and with trained staff for cessation counseling. Conclusions: Current physician self-reported practices for smoking cessation suggest opportunity for improvement. Targeted efforts to educate and support subsets of primary care physicians may improve physician adherence and smoking outcomes. C1 Univ Penn, Dept Psychiat, Transdisciplinary Tobacco Use Res Ctr, Philadelphia, PA 19104 USA. Geisinger Hlth Syst, Danville, PA USA. Harvard Univ, Massachusetts Gen Hosp, Inst Hlth Policy Res, Boston, MA 02114 USA. RP Schnoll, RA (reprint author), Univ Penn, Dept Psychiat, Transdisciplinary Tobacco Use Res Ctr, 3535 Market St,Suite 4100, Philadelphia, PA 19104 USA. EM schnoll@mail.med.upenn.edu FU PHS HHS [P50 84718] NR 57 TC 56 Z9 57 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2006 VL 31 IS 3 BP 233 EP 239 DI 10.1016/j.amepre.2006.05.001 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 077QM UT WOS:000240044800006 PM 16905034 ER PT J AU Nierenberg, AA Fava, M Trivedi, MH Wisniewski, SR Thase, ME McGrath, PJ Alpert, JE Warden, D Luther, JF Niederehe, G Lebowitz, B Shores-Wilson, K Rush, AJ AF Nierenberg, Andrew A. Fava, Maurizio Trivedi, Madhukar H. Wisniewski, Stephen R. Thase, Michael E. McGrath, Patrick J. Alpert, Jonathan E. Warden, Diane Luther, James F. Niederehe, George Lebowitz, Barry Shores-Wilson, Kathy Rush, A. John CA STAR D Study Team TI A comparison of lithium and T-3 augmentation following two failed medication treatments for depression: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE; INTERACTIVE VOICE RESPONSE; ILLNESS RATING-SCALE; REPORT QIDS-SR; TRIIODOTHYRONINE AUGMENTATION; REFRACTORY DEPRESSION; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS AB Objective: More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T-3) augmentation as a third-step treatment for patients with major depressive disorder. Method: A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T-3 (up to 50 mu g/day; N= 73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score <= 7 on the 17-item Hamilton Depression Rating Scale. Results: After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T-3 augmentation, although the difference between treatments was not statistically significant. Lithium was more frequently associated with side effects (p=0.045), and more participants in the lithium group left treatment because of side effects (23.2% versus 9.6%; p=0.027). Conclusions: Remission rates with lithium and T-3 augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. The lower side effect burden and ease of use of T-3 augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. NIMH, Bethesda, MD 20892 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St, Boston, MA 02114 USA. EM anierenberg@partners.org RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH-90003] NR 49 TC 205 Z9 209 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2006 VL 163 IS 9 BP 1519 EP 1530 DI 10.1176/appi.ajp.163.9.1519 PG 12 WC Psychiatry SC Psychiatry GA 079VD UT WOS:000240205100011 PM 16946176 ER PT J AU McGrath, PJ Stewart, JW Fava, M Trivedi, MH Wisniewski, SR Nierenberg, AA Thase, ME Davis, L Biggs, MM Shores-Wilson, K Luther, JF Niederehe, G Warden, D Rush, AJ AF McGrath, Patrick J. Stewart, Jonathan W. Fava, Maurizio Trivedi, Madhukar H. Wisniewski, Stephen R. Nierenberg, Andrew A. Thase, Michael E. Davis, Lori Biggs, Melanie M. Shores-Wilson, Kathy Luther, James F. Niederehe, George Warden, Diane Rush, A. John CA STAR D Study Team TI Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DIAGNOSTIC SCREENING QUESTIONNAIRE; SEQUENCED TREATMENT ALTERNATIVES; TREATMENT-RESISTANT DEPRESSION; INTERACTIVE VOICE RESPONSE; VAGUS NERVE-STIMULATION; ILLNESS RATING-SCALE; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; MAJOR DEPRESSION; QUICK INVENTORY AB Objective: The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials. Method: Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine (N=51). The primary outcome measure was whether patients achieved remission, which was defined as a score <= 7 at exit on the 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D was administered by telephone by raters to whom treatment was masked. Results: Remission rates were not significantly different between the two treatment groups (6.9% for the tranylcypromine group and 13.7% for the venlafaxine plus mirtazapine group). The mean daily dose at exit for tranylcypromine was 36.9 mg (SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and for mirtazapine, 35.7 mg (SD=17.6). Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance. Conclusions: Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments. C1 New York State Psychiat Inst & Hosp, Depress Evaluat Serv, New York, NY 10032 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Austin, TX USA. Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Columbia Coll Phys & Surg, Dept Psychiat, New York, NY USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15260 USA. NIMH, Bethesda, MD 20892 USA. RP McGrath, PJ (reprint author), New York State Psychiat Inst & Hosp, Depress Evaluat Serv, 1051 Riverside Dr,Unit 51, New York, NY 10032 USA. EM mcgrath@pi.cpmc.columbia.edu RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH-90003] NR 40 TC 171 Z9 177 U1 1 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2006 VL 163 IS 9 BP 1531 EP 1541 DI 10.1176/appi.ajp.163.9.1531 PG 11 WC Psychiatry SC Psychiatry GA 079VD UT WOS:000240205100012 PM 16946177 ER PT J AU McGrath, PJ Stewart, JW Quitkin, FM Ying, C Alpert, JE Nierenberg, AA Fava, M Cheng, JF Petkova, E AF McGrath, Patrick J. Stewart, Jonathan W. Quitkin, Frederic M. Ying Chen Alpert, Jonathan E. Nierenberg, Andrew A. Fava, Maurizio Cheng, Jianfeng Petkova, Eva TI Predictors of relapse in a prospective study of fluoxetine treatment of major depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PATTERN-ANALYSIS; RECURRENT DEPRESSION; MAINTENANCE THERAPIES; PREVENTION; CONTINUATION; PLACEBO; PAROXETINE; IMIPRAMINE; DISORDERS; UNIPOLAR AB Objective: Loss of response to a previously effective antidepressant is a common clinical problem. Retrospective analyses have shown that the pattern of response during antidepressant treatment (late onset and persistent versus other patterns) can be used to predict relapse during continuation and maintenance treatment and possibly to identify placebo responses to treatment. This study was designed to test the predictive value of response pattern prospectively and to examine the data for other predictors of relapse. Method: Five hundred seventy persons with major depressive disorder were treated with fluoxetine for 12 weeks and their pattern of response was determined. Those who responded (N=292) underwent random assignment, under double-blind conditions, to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse. Survival analysis was used to examine the effect of covariates on relapse. Results: Although fluoxetine was significantly more effective than placebo during maintenance treatment, this chronically ill group had a high rate of relapse. Contrary to previous findings, a pattern of acute response was not predictive of relapse. Chronicity, symptom severity, a neurovegetative symptom pattern, and female gender were all associated with a significantly greater risk of relapse, with no difference observed between fluoxetine and placebo. Conclusions: The pattern of response to acute treatment appears to be inconsistently predictive of relapse. There is a high rate of relapse with both active medication and placebo in patients with chronic depression. Illness characteristics predict loss of response both to fluoxetine and to placebo. No variable examined was predictive of differential relapse rates between fluoxetine and placebo. C1 New York State Psychiat Inst & Hosp, Depress Evaluat Serv, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McGrath, PJ (reprint author), New York State Psychiat Inst & Hosp, Depress Evaluat Serv, 1051 Riverside Dr,Unit 51, New York, NY 10032 USA. EM mcgrath@pi.cpmc.columbia.edu RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01-MH56058] NR 31 TC 60 Z9 64 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2006 VL 163 IS 9 BP 1542 EP 1548 DI 10.1176/appi.ajp.163.9.1542 PG 7 WC Psychiatry SC Psychiatry GA 079VD UT WOS:000240205100013 PM 16946178 ER PT J AU Kramer, BJ Wang, MM Hoang, T Harker, JO Finke, B Saliba, D AF Kramer, B. Josea Wang, Mingming Hoang, Tuyen Harker, Judith O. Finke, Bruce Saliba, Debra TI Identification of American Indian and Alaska native veterans in administrative data of the veterans health administration and the Indian health service SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB We sought to determine the extent to which the Indian Health Service (IHS) identified enrollees who also use the Veterans Health Administration (VHA) as veterans. We used a bivariate analysis of administrative data from fiscal years 20022003 to study the target population. Of the 32259 IHS enrollees who received care as veterans in the VHA, only 44% were identified by IHS as veterans. IHS data underestimates the number of veterans, and both IHS and VHA need mechanisms to recognize mutual beneficiaries in order to facilitate better coordination of strategic planning and resource sharing among federal health care agencies. C1 Vet Affairs Greater Los Angeles Healthcare Syst, GRECC, Dept Vet Affairs, North Hills, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. Ctr Geriatr Res Educ & Clin, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Indian Hlth Serv, Elder Care Initiat, Northampton, MA USA. RAND Corp, Los Angeles, CA USA. RP Kramer, BJ (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, GRECC, Dept Vet Affairs, 16 111 Plummer St,11E, North Hills, CA 91343 USA. EM josea.kramer@va.gov NR 8 TC 3 Z9 3 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2006 VL 96 IS 9 BP 1577 EP 1578 DI 10.2105/AJPH.2005.073205 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 079LY UT WOS:000240179100016 PM 16873744 ER PT J AU Bennett, GG Wolin, KY Viswanath, K Askew, S Puleo, E Emmons, KM AF Bennett, Gary G. Wolin, Kathleen Y. Viswanath, K. Askew, Sandy Puleo, Elaine Emmons, Karen M. TI Television viewing and pedometer-determined physical activity among multiethnic residents of low-income housing SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID TYPE-2 DIABETES-MELLITUS; HEALTH-PROFESSIONALS; AMERICAN CHILDREN; PUBLIC-HEALTH; UNITED-STATES; RISK-FACTORS; OBESITY; OVERWEIGHT; WOMEN; RECOMMENDATIONS AB Objectives. We evaluated the association between television viewing and pedometer-determined physical activity among predominantly racial/ethnic minority residents of low-income housing in metropolitan Boston in 2005. Methods. We used mixed models to analyze the association between reported hours of television viewing and pedometer-determined steps per day among 486 adults. We also examined whether television viewing was associated with the achievement of 10000 steps per day. Results. There was a mean 3.6 hours of average daily television watching. In multivariable analyses, each hour of television viewing on an average day was associated with 144 (95% confidence interval [CI] =-276, -12) fewer steps per day and a decreased likelihood of accumulating 10000 steps per day (odds ratio [OR] = 0.84; 95% Cl = 0.71, 0.99). Weekday and weekend television viewing were each also associated with fewer steps per day. Conclusions. Average daily television viewing was associated with reductions in total pedometer-determined physical activity levels (approximately 520 steps per day) in this lower-income sample. As part of a comprehensive physical activity promotion plan, recommendations to reduce television viewing should be made. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA USA. Univ Massachusetts, Dept Publ Hlth Biostat & Epidemiol Concentrat, Amherst, MA USA. RP Bennett, GG (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,Smith 256, Boston, MA 02115 USA. EM gary_bennett@dfci.harvard.edu FU NCI NIH HHS [3R01CA098864-02S1, 5R01CA098864-02, T32 CA009001, R01 CA098864, 5 T32 CA09001-28] NR 33 TC 21 Z9 23 U1 4 U2 8 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2006 VL 96 IS 9 BP 1681 EP 1685 DI 10.2105/AJPH.2005.080580 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 079LY UT WOS:000240179100034 PM 16873736 ER PT J AU Barker, GF Manzo, ND Cotich, KL Shone, RK Waxman, AB AF Barker, George F. Manzo, Nicholas D. Cotich, Kara L. Shone, Robin K. Waxman, Aaron B. TI DNA damage induced by hyperoxia - Quantitation and correlation with lung injury SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE 8-oxoguanine; acute lung injury; apoptosis; DNA damage; hyperoxia ID ENHANCES MURINE TOLERANCE; ALVEOLAR EPITHELIAL-CELLS; COMET ASSAY; 100-PERCENT OXYGEN; MAMMALIAN-CELLS; MOUSE LUNG; II CELLS; EXPRESSION; APOPTOSIS; DEATH AB Inspired oxygen, an essential therapy for cardiorespiratory disorders, has the potential to generate reactive oxygen species that damage cellular DNA. Although DNA damage is implicated in diverse pulmonary disorders, including neoplasia and acute lung injury, the type and magnitude of DNA lesion caused by oxygen in vivo is unclear. We used single-cell gel electrophoresis (SCGE) to quantitate two distinct forms of DNA damage, base adduction and disruption of the phosphodiester backbone, in the lungs of mice. Both lesions were induced by oxygen, but a marked difference between the two was found. With 40 h of oxygen exposure, oxidized base adducts increased 3- to 4-fold in the entire population of lung cells. This lesion displayed temporal characteristics (a progressive increase over the first 24 h) consistent with a direct effect of reactive oxygen species attack upon DNA. DNA strand breaks, on the other hand, occurred in < 10% of pulmonary cells, which acquired severe levels of the lesion; dividing cells were preferentially affected. Characteristics of these cells suggested that DNA strand breakage was secondary to cell death, rather than a primary effect of reactive oxygen species attack on DNA. By analysis of IL-6- and IL-11-overexpressing transgenic animals, which are resistant to hyperoxia, we found that DNA strand breaks, but not base damage, correlated with acute lung injury. Analysis of purified alveolar type 2 preparations from hyperoxic mice indicated that strand breaks preferentially affected this cell type. C1 Harvard Univ, Sch Med, Dept Med, Pulm & Crit Care Unit,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Barker, GF (reprint author), Harvard Univ, Sch Med, Dept Med, Pulm & Crit Care Unit,Massachusetts Gen Hosp, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM GBarker@Partners.org FU NHLBI NIH HHS [HL03888-01, HL074859] NR 41 TC 40 Z9 45 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 2006 VL 35 IS 3 BP 277 EP 288 DI 10.1165/rcmb.2005-0340OC PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 080PU UT WOS:000240260800001 PM 16574945 ER PT J AU Gervais, DA Arellano, RS Mueller, PR AF Gervais, Debra A. Arellano, Ronald S. Mueller, Peter R. TI Percutaneous radiofrequency ablation of ovarian cancer metastasis to the liver: Indications, outcomes, and role in patient management SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE oncology; ovarian neoplasm; percutaneous ablation; radiofrequency ablation ID SURGICAL CYTOREDUCTION; SURGERY; CARCINOMA; TUMORS AB OBJECTIVE. Stages III and IV ovarian cancer are treated with a combination of chemotherapy and resection, in some cases including second and third surgical procedures, to achieve cytoreduction. Percutaneous radiofrequency ablation has proved effective in local control of hepatic tumors. We report early experience with percutaneous radiofrequency ablation in the management of isolated foci of metastatic ovarian cancer and assess the efficacy of the technique in achieving and maintaining local control by percutaneous cytoreduction. CONCLUSION. Percutaneous radiofrequency ablation is effective in achieving local control in selected patients with metastasis from ovarian cancer. In patients with limited macroscopic disease, cytoreduction can be achieved without surgery. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 12 TC 13 Z9 13 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2006 VL 187 IS 3 BP 746 EP 750 DI 10.2214/AJR.05.1106 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 080PF UT WOS:000240259300026 PM 16928940 ER PT J AU Lee, SI AF Lee, Susanna I. TI Radiological reasoning: Imaging characterization of bilateral adnexal masses SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adnexa; genitourinary imaging; MRI; ovaries; pelvic imaging; sonography; uterus; women's imaging ID HEMORRHAGIC OVARIAN CYSTS; DEEP PELVIC ENDOMETRIOSIS; POSTMENOPAUSAL WOMEN; SONOGRAPHIC FINDINGS; GRAY-SCALE; PATHOLOGICAL CORRELATION/; TRANSVAGINAL SONOGRAPHY; COLOR DOPPLER; CANCER; DIAGNOSIS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lee, SI (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM slee0@partners.org NR 32 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2006 VL 187 IS 3 SU S BP S460 EP S466 DI 10.2214/AJR.05.2226 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 082RU UT WOS:000240405700002 PM 16928898 ER PT J AU Lee, SI AF Lee, Susanna I. TI Imaging evaluation of adnexal masses: Self-assessment module SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE adnexal masses; genitourinary tract imaging; MRI; reproductive organ imaging; sonography ID SONOGRAPHY; ENDOMETRIOSIS; CYSTS AB The educational objectives for this self-assessment module on adnexal masses are for the participant to exercise, self-assess, and improve his or her knowledge of the imaging evaluation of adnexal masses and to gain familiarity with the features of adnexal masses on sonography and MRI that characterize them as benign. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lee, SI (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM slee0@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2006 VL 187 IS 3 SU S BP S457 EP S459 DI 10.2214/AJR.06.0785 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 082RU UT WOS:000240405700001 ER PT J AU Johnson, ML Bush, RL Collins, TC Lin, PH Liles, DR Henderson, WG Khuri, SF Petersen, LA AF Johnson, Michael L. Bush, Ruth L. Collins, Tracie C. Lin, Peter H. Liles, Debra R. Henderson, William G. Khuri, Shukri F. Petersen, Laura A. TI Propensity score analysis in observational studies: outcomes after abdominal aortic aneurysm repair SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE outcomes; abdominal aortic aneurysm; endovascular ID RANDOMIZED CONTROLLED-TRIAL; ENDOVASCULAR REPAIR; RISK; MORTALITY; SURGERY; CARE AB Objective: Large databases composed of well-designed prospectively collected cohort data provide an opportunity to examine and compare healthcare treatments in actual clinical practice settings. Because the analysis of these data often leads to a retrospective cohort design, it is essential to adequately adjust for lack of balance in patient characteristics when making treatment comparisons. We used matched propensity scoring in a cohort of patients undergoing elective aneurysm repair as an illustrative example of this important statistical method that adjusts for baseline characteristics and selection bias by matching covariables. Methods: By using prospectively collected clinical data from the National Surgical Quality Improvement Program of the Department of Veterans Affairs, we studied 30-day mortality, I-year survival, and postoperative complications in 1904 patients who underwent elective AAA repair (endovascular aneurysm repair [EVAR], n = 717 (37.7%); open aneurysm repair, n = 1187 [62.3%]) at 123 Veterans Health Administration's hospitals between May 1, 2001, and September 30, 2003. In bivariate analysis, patient characteristics and operative and hospital variables were associated with both type of surgery and outcomes of surgery. Therefore, the predicted probability of receiving EVAR was tabulated for all patients by using multiple logistic regression to control for 32 independent demographic and clinical characteristics and then stratified into 5 groups. Patients were matched within strata based on similar levels of the independent measures (a propensity score technique), creating a pseudo-randomized control design. The proportion of patients with the morbidity and mortality outcomes was then compared between the EVAR and open procedures within strata to control for selection. Results: Patients undergoing EVAR had significantly lower unadjusted 30-day (3.1% versus 5.6%, P = .01) and 1-year mortality (8.7% versus 12.1%, P = .0 18) than patients undergoing open repair. By using propensity scoring, the proportions of EVAR patients experiencing 30-day mortality were equal or less than patients undergoing open procedures for all levels of probability and decreased as the probability of EVAR increased. Furthermore, propensity scoring also showed that patients having EVAR had lower 1-year mortality and experienced fewer perioperative complications. Conclusions: We used a propensity score approach to examine outcomes after,elective AAA repair to statistically control for many factors affecting both treatment selection and outcome. Patients who underwent elective EVAR had substantially lower perioperative mortality and morbidity rates compared with patients having open repair, which was not explained solely by patient selection in an observational dataset. (c) 2006 Excerpta Medica Inc. All rights reserved. C1 Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Houston VAMC, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Bush, RL (reprint author), Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. EM rbush@bcm.tmc.edu NR 24 TC 23 Z9 23 U1 0 U2 1 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2006 VL 192 IS 3 BP 336 EP 343 DI 10.1016/j.amjsurg.2006.03.009 PG 8 WC Surgery SC Surgery GA 079LD UT WOS:000240176900013 PM 16920428 ER PT J AU Ogino, S Odze, RD Kawasaki, T Brahmandam, M Kirkner, GJ Laird, PW Loda, M Fuchs, CS AF Ogino, Shuji Odze, Robert D. Kawasaki, Takako Brahmandam, Mohan Kirkner, Gregory J. Laird, Peter W. Loda, Massimo Fuchs, Charles S. TI Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE colon cancer; epigenetics; promoter; hypermethylation; histopathology ID TIME PCR ASSAY; COLON-CANCER; MICROSATELLITE INSTABILITY; PROMOTER REGION; HYPERMETHYLATION; ADENOCARCINOMA; MUTATION; TUMORS; EPIGENETICS; PROFILES AB Extensive gene promoter methylation in colorectal carcinoma has been termed the CpG island methylator phenotype (CIMP). Previous studies on CIMP used primarily methylation-specific polymerase chain reaction (PCR), which, unfortunately, may detect low levels of methylation that has little or no biological significance. Utilizing quantitative real-time PCR (MethyLight), we measured DNA methylation in a panel of 5 CIMP-specific gene promoters (CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 459 colorectal carcinomas obtained from 2 large prospective cohort studies. CIMP was defined as tumors that showed methylation in >= 4/5 promoters. CIMP was significantly associated with the presence of mucinous or signet ring cell morphology, marked Crohn's-like lymphoid reaction, tumor infiltrating lymphocytes, marked peritumoral lymphocytic reaction, tumor necrosis, tumor cell sheeting, and poor differentiation. All these features have previously been associated with microsatellite instability (MSI). Therefore, we divided the 459 colorectal carcinomas into 6 subtypes, namely, MSI-high (MSI-H)/CIMP, MSI-H/non-CIMP, MSI-low (MSI-L)/CIMP, MSI-L/non-CIMP, microsatellite stable/CIMP, and micro satellite sstable/non-CIMP. Compared with MSI-H/non-CIMP, MSI-H/CIMP was associated with marked tumor infiltrating lymphocytes, tumor necrosis, sheeting, and poor differentiation (all P <= 0.05). Compared with MSI-L/non-CIMP, MSI-L/CIMP was associated with tumors that had < 50% signet ring cell component, marked tumor infiltrating lymphocytes, and poor differentiation (all P < 0.05). In conclusion, several pathologic features that have previously been shown to be associated with MST are also significantly associated with CIMP. Both MSI and CIMP appear to play a role in the pathogenesis of specific morphologic patterns of colorectal carcinoma. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu RI Laird, Peter/G-8683-2012 FU NCI NIH HHS [P01 CA55075-13, P01 CA87969-03, R01 CA075090] NR 43 TC 60 Z9 62 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2006 VL 30 IS 9 BP 1175 EP 1183 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 082TL UT WOS:000240410000014 PM 16931963 ER PT J AU Fudaba, Y Spitzer, TR Shaffer, J Kawai, T Fehr, T Delmonico, F Preffer, F Tolkoff-Rubin, N Dey, BR Saidman, SL Kraus, A Bonnefoix, T McAfee, S Power, K Kattleman, K Colvin, RB Sachs, DH Cosimi, AB Sykes, M AF Fudaba, Y. Spitzer, T. R. Shaffer, J. Kawai, T. Fehr, T. Delmonico, F. Preffer, F. Tolkoff-Rubin, N. Dey, B. R. Saidman, S. L. Kraus, A. Bonnefoix, T. McAfee, S. Power, K. Kattleman, K. Colvin, R. B. Sachs, D. H. Cosimi, A. B. Sykes, M. TI Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: In vivo and in vitro analyses SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE bone marrow transplantation; kidney; limiting dilution assay; mixed chimerism; multiple myeloma; tolerance ID STEM-CELL TRANSPLANTATION; REFRACTORY HEMATOLOGIC MALIGNANCIES; MIXED LYMPHOHEMATOPOIETIC CHIMERISM; RECIPIENT LEUKOCYTE INFUSIONS; RENAL-ALLOGRAFT REJECTION; LIMITING DILUTION ASSAYS; DONOR-SPECIFIC TOLERANCE; BONE-MARROW; MULTIPLE-MYELOMA; CYNOMOLGUS MONKEYS AB Six patients with renal failure due to multiple myeloma (MM) received simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical sibling donors following nonmyeloablative conditioning, including cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic irradiation. Cyclosporine (CyA) was given for approximately 2 months posttransplant, followed by donor leukocyte infusions. All six patients accepted their kidney grafts long-term. Three patients lost detectable chimerism but accepted their kidney grafts off immunosuppression for 1.3 to > 7 years. One such patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in association with marrow rejection. Two patients achieved full donor chimerism, but resumed immunosuppression to treat graft-versus-host disease. Only one patient experienced rejection following CyA withdrawal. He responded to immunosuppression, which was later successfully withdrawn. The rejection episode was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness to cultured donor renal tubular epithelial cells. Initially recovering T cells were memory cells and were enriched for CD4(+)CD25(+) cells. Three patients are in sustained complete remissions of MM, despite loss of chimerism in two. Combined kidney/BMT with nonmyeloablative conditioning can achieve renal allograft tolerance and excellent myeloma responses, even in the presence of donor marrow rejection and antidonor alloresponses in vitro. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH E, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Unit, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Bone Marrow Transplant Unit, Boston, MA 02115 USA. INSERM, U353, Inst Albert Bonniot, F-38000 Grenoble, France. Univ Grenoble 1, F-38000 Grenoble, France. CHRU, Federat Oncohematol, Hop Michallon, F-38000 Grenoble, France. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH E, Dept Surg,Transplantat Biol Res Ctr, Bldg 149-5102,13th St, Boston, MA 02115 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL63474]; NIAID NIH HHS [R01 AI037692, R01 AI037692-09, R01 AI037692-10, R21 AI037692, R21 AI037692-06] NR 45 TC 188 Z9 200 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2006 VL 6 IS 9 BP 2121 EP 2133 DI 10.1111/j.1600-6143.2006.01434.x PG 13 WC Surgery; Transplantation SC Surgery; Transplantation GA 071QX UT WOS:000239617800015 PM 16796719 ER PT J AU Hill, DR Baird, JK Parise, ME Lewis, LS Ryan, ET Magill, AJ AF Hill, David R. Baird, J. Kevin Parise, Monica E. Lewis, Linda S. Ryan, Edward T. Magill, Alan J. TI Primaquine: Report from CDC expert meeting on malaria chemoprophylaxis I SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Review ID PLASMODIUM-VIVAX MALARIA; PNEUMOCYSTIS-CARINII PNEUMONIA; PLACEBO-CONTROLLED TRIAL; NONIMMUNE COLOMBIAN SOLDIERS; DRUG-INDUCED ENDOCYTOSIS; HUMAN LIVER-MICROSOMES; ANTI-RELAPSE THERAPY; ANTIMALARIAL-DRUGS; TRIMETHOPRIM-SULFAMETHOXAZOLE; INDUCED METHEMOGLOBINEMIA AB Primaquine phosphate has been used for preventing relapse of Plasmodium vivax and P. ovate malaria since the early 1950s, based on its ability to kill latent (hypnozoite) and developing liver stages of these parasites. There are three uses for primaquine in malaria: radical cure of established infection with P. vivax or P. ovate malaria; presumptive anti-relapse therapy (PART; terminal prophylaxis) in persons with extensive exposure to these parasites; and primary prophylaxis against all malaria species. All persons for whom primaquine is being considered must have a glucose-6-phosphate dehydrogenase (G6PD) enzyme level checked before use, and persons who have a deficiency of G6PD must not take primaquine for prophylaxis or PART. The recommended adult dose for PART based on clinical trials and expert opinion is 30 mg base daily for 14 days, started on return from a malarious region and overlapping with a blood schizonticide. The adult dose for primary prophylaxis is 30 mg daily begun 1 day before travel and continued for 7 days after return. This review will examine the evidence for these recommendations. C1 Natl Travel Hlth Network, DTM&H, London WC1E 6AU, England. London Sch Hyg & Trop Med, London WC1E 6AU, England. ALERTAsia Fdn, Jakarta 10430, Indonesia. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, US Publ Hlth Serv, Atlanta, GA 30341 USA. Butte Cty Dept Publ Hlth, Oroville, CA 95965 USA. Massachusetts Gen Hosp, Trop & Geog Med Ctr, Div Infect Dis, Boston, MA 02114 USA. Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. RP Hill, DR (reprint author), Natl Travel Hlth Network, DTM&H, Capper St, London WC1E 6AU, England. EM david.hill@uclh.org NR 170 TC 149 Z9 153 U1 0 U2 9 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2006 VL 75 IS 3 BP 402 EP 415 PG 14 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 083RR UT WOS:000240476400006 PM 16968913 ER PT J AU McFall, M Atkins, DC Yoshimoto, D Thompson, CE Kanter, E Malte, CA Saxon, AJ AF McFall, Miles Atkins, David C. Yoshimoto, Dan Thompson, Charles E. Kanter, Evan Malte, Carol A. Saxon, Andrew J. TI Integrating tobacco cessation treatment into mental health care for patients with posttraumatic stress disorder SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID PREDICTING SMOKING CESSATION; PLACEBO-CONTROLLED TRIAL; VIETNAM COMBAT VETERANS; MAJOR DEPRESSION; FOLLOW-UP; DEPENDENCE TREATMENT; NICOTINE DEPENDENCE; SCHIZOPHRENIA; SMOKERS; INTERVENTION AB The integration of tobacco cessation treatment into mental health care for posttraumatic stress disorder (PTSD), known as Integrated Care (IC), was evaluated in an uncontrolled feasibility and effectiveness study. Veterans (N = 107) in PTSD treatment at two outpatient clinics received IC delivered by mental health practitioners. Outcomes were seven-day point prevalence abstinence measured at two, four, six, and nine months post-enrollment and repeated seven-day point prevalence abstinence (RPPA) obtained across three consecutive assessment intervals (four, six, and nine months). Abstinence rates at the four assessment intervals were 28%, 23%, 25%, and 18%, respectively, and RPPA was 15%. The number of IC sessions and a previous quit history greater than six months predicted RPPA. Stopping smoking was not associated with worsening PTSD or depression. C1 NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. RP McFall, M (reprint author), VA Puget Sound Hlth Care Syst, PTSD Programs S116 MHC, 1660 S Columbian Way, Seattle, WA 98108 USA. EM miles.mcfall@va.gov OI Atkins, David/0000-0002-5781-9880 NR 60 TC 27 Z9 27 U1 2 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2006 VL 15 IS 5 BP 336 EP 344 DI 10.1080/10550490600859892 PG 9 WC Substance Abuse SC Substance Abuse GA 083DN UT WOS:000240436200002 PM 16966189 ER PT J AU Harned, MS Najavits, LM Weiss, RD AF Harned, Melanie S. Najavits, Lisa M. Weiss, Roger D. TI Self-harm and suicidal behavior in women with comorbid PTSD and substance dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DISORDER; REASONS; SAMPLE AB This study examined the frequency, methods, and correlates of self-harm and suicidal behavior in 65 outpatient women with comorbid posttraumatic stress disorder (PTSD) and substance dependence (SD). Results showed high rates of suicide attempts, self-harm, suicidal ideation, and self-harm ideation for the prior three months. The most common methods were overdosing and cutting/scratching. Both PTSD and SD were perceived as contributing to self-harm and suicidal behavior. Women who had and had not engaged in such behavior differed in SD diagnoses and reasons for staying safe, but not in the number or type of traumatic experiences, age at first trauma, or substance abuse diagnoses. C1 Univ Washington, Dept Psychol, Seattle, WA 98195 USA. McLean Hosp, Trauma Res Program, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. McLean Hosp, Alcohol & Drug Abuse Treatment Program, Belmont, MA 02178 USA. RP Harned, MS (reprint author), Univ Washington, Dept Psychol, BOX 351525, Seattle, WA 98195 USA. EM mharned@brtc.psych.washington.edu FU NIDA NIH HHS [K02-DA00326, R01-DA08631, K02-DA00400, R01-DA15968] NR 12 TC 30 Z9 31 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2006 VL 15 IS 5 BP 392 EP 395 DI 10.1080/10550490600860387 PG 4 WC Substance Abuse SC Substance Abuse GA 083DN UT WOS:000240436200009 PM 16966196 ER PT J AU Velmahos, GC AF Velmahos, George C. TI The current status of thromboprophylaxis after trauma: A story of confusion and uncertainty SO AMERICAN SURGEON LA English DT Article ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; INTERMITTENT PNEUMATIC COMPRESSION; LOW-DOSE HEPARIN; VENA-CAVAL FILTERS; VENOUS THROMBOEMBOLISM; MAJOR TRAUMA; PULMONARY-EMBOLISM; MANAGEMENT GUIDELINES; COST-EFFECTIVENESS AB It is difficult to support a standard of care for venous thromboprophylaxis after trauma when there is no convincing research that any of the currently used methods is consistently effective. Because many conclusions from the nontrauma literature have been misleadingly extrapolated to trauma patients, this review focuses exclusively on trauma articles. These articles present variable results. The rates of deep venous thrombosis and pulmonary embolism are widely different even among similar trauma populations. The heparin-unfractionated or low-molecular-weight and calf compression methods fail to show a reproducible effect in decreasing venous thromboembolic events. The current methods of venous thromboprophylaxis after trauma are inadequate and further research in this area is direly needed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 53 TC 13 Z9 13 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD SEP PY 2006 VL 72 IS 9 BP 757 EP 763 PG 7 WC Surgery SC Surgery GA 082IB UT WOS:000240378800001 PM 16986383 ER PT J AU Qureshi, MM Hayden, D Urbinelli, L Ferrante, K Newhall, K Myers, D Hilgenberg, S Smart, R Brown, RH Cudkowicz, ME AF Qureshi, M. Muddasir Hayden, Douglas Urbinelli, Leo Ferrante, Kimberly Newhall, Kristyn Myers, Daniela Hilgenberg, Sarah Smart, Ryan Brown, Robert H., Jr. Cudkowicz, Merit E. TI Analysis of factors that modify susceptibility and rate of progression in amyotrophic lateral sclerosis (ALS) SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE amyotrophic lateral sclerosis; motor neuron disease; epidemiology; risk factors; disease progression ID MOTOR-NEURON-DISEASE; HYDROXYLASE GENE POLYMORPHISM; FUNCTIONAL RATING-SCALE; GULF-WAR VETERANS; RISK-FACTORS; NATURAL-HISTORY; ANTECEDENT EVENTS; CIGARETTE-SMOKING; POPULATION; TRAUMA AB We conducted case-control and prospective longitudinal studies to examine risk factors and predictors of disease progression for ALS. Ninety-five subjects with ALS and 106 healthy control subjects were enrolled. All subjects completed a risk factor questionnaire at enrollment. The ALS subjects were prospectively followed for one year to define factors that influence the rate of disease progression, measured by rate of change in percent predicted forced vital capacity (%FVC) and the ALS functional rating scale (ALSFRS) score. The association of each potential risk factor with ALS was determined using univariate logistic regression. A random slope model was used to determine the association of each risk factor with disease progression. The demographic characteristics of ALS subjects and controls at enrollment did not differ. Significant risk factors for ALS included reported exposure to lead (p=0.02) and pesticides (p=0.03). Disease progression was faster in the ALS subjects having bulbar onset and a shorter time period between onset of symptoms and diagnosis. Pertinent variables not associated with either causation or progression of ALS included physical activity, cigarette smoking and a history of physical trauma or other clinical disorders. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Biostat Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Boston, MA USA. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, East Bldg 14,13th St,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org OI Ferrante, Kimberly/0000-0002-6069-9226 FU NINDS NIH HHS [K08 NS001896] NR 90 TC 64 Z9 66 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD SEP PY 2006 VL 7 IS 3 BP 173 EP 182 DI 10.1080/14660820600640596 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 093FQ UT WOS:000241153900007 PM 16963407 ER PT J AU Zhang, JH Kawashima, S Yokoyama, M Huang, P Hill, CE AF Zhang, Jian Hong Kawashima, Seinosuke Yokoyama, Mitsuhiro Huang, Paul Hill, Caryl E. TI Increased eNOS accounts for changes in connexin expression in renal arterioles during diabetes SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article DE eNOS; connexin; renal arterioles; diabetes ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL NO SYNTHASE; EFFERENT ARTERIOLES; GAP-JUNCTIONS; ANGIOTENSIN-II; BLOOD-FLOW; CELLS; MICE; RAT; STREPTOZOTOCIN AB Previous studies have shown that connexin (Cx) expression is considerably higher in the preglomerular compared to postglomerular vasculature and that these differences are accentuated during diabetes. Since nitric oxide (NO) has been reported to alter Cx expression in endothelial cells and muscle cells and NO bioavailability is altered in diabetes, we hypothesized that NO may be responsible for the changes during diabetes. Cx expression was studied using immunohistochemistry in mice in which eNOS expression was either upregulated (eNOS transgenic) or downregulated (eNOS knockout). Diabetes was induced intraperitoneally with a single dose of alloxan or multiple low doses of streptozotocin. Expression of Cx40 in smooth muscle cells of afferent arterioles was increased, while expression of Cx43 in endothelial cells of efferent arterioles was absent in eNOS transgenic mice, similar to the changes occurring in wild-type mice during diabetes. Expression of Cx40 and Cx43 in eNOS knockout mice was not different from control; however, induction of diabetes in eNOS knockout mice failed to produce any changes in Cx40 or Cx43 in either afferent or efferent arterioles. Immunohistochemistry showed that eNOS expression was increased in the endothelium of renal arterioles in wild-type diabetic and eNOS transgenic mice, but absent from arterioles of eNOS knockout mice. We conclude that changes occurring in Cx expression in afferent and efferent arterioles during diabetes may result from increased eNOS. C1 Australian Natl Univ, Div Neurosci, John Curtin Sch Med Res, Canberra, ACT 2602, Australia. Kobe Univ, Sch Med, Dept Internal Med 1, Kobe, Hyogo 650, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Hill, CE (reprint author), Australian Natl Univ, Div Neurosci, John Curtin Sch Med Res, Canberra, ACT 2602, Australia. EM caryl.hill@anu.edu.au RI Hill, Caryl/D-8972-2011 NR 43 TC 17 Z9 18 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4884 J9 ANAT REC PART A JI Anat. Rec. Part A PD SEP PY 2006 VL 288A IS 9 BP 1000 EP 1008 DI 10.1002/ar.a.20369 PG 9 WC Anatomy & Morphology SC Anatomy & Morphology GA 081CS UT WOS:000240295400009 PM 16892422 ER PT J AU Forman, SA AF Forman, Stuart A. TI Of mice and nematodes SO ANESTHESIOLOGY LA English DT Editorial Material ID D-ASPARTATE RECEPTOR; CAENORHABDITIS-ELEGANS; VOLATILE-ANESTHETICS; CONTROLS-SENSITIVITY C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM saforman@partners.org NR 13 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2006 VL 105 IS 3 BP 442 EP 444 DI 10.1097/00000542-200609000-00003 PG 3 WC Anesthesiology SC Anesthesiology GA 078OE UT WOS:000240112300002 PM 16931973 ER PT J AU Montero-Huerta, P Hess, DR Head, A AF Montero-Huerta, Pedro Hess, Dean R. Head, Alvin TI Inhaled nitric oxide for treatment of sickle cell stroke SO ANESTHESIOLOGY LA English DT Article ID CEREBRAL VASCULOPATHY; TRANSCRANIAL DOPPLER; OXYGEN-AFFINITY; DISEASE; ANEMIA; ERYTHROCYTES; SYNTHASE; BIOAVAILABILITY; HEMOGLOBIN; MECHANISMS AB STROKE is a highly fatal complication of sickle cell disease (SCD) in children, particularly between the ages of 4 and 15 yr. Children with SCD carry a 300-fold increased risk for stroke; consequently, sickle cell anemia is the most common cause of childhood stroke.(1) We report the case of a 13-yr-old African-American boy diagnosed at age 6 months old with hemoglobin SS disease, who had a nonhemorrhagic stroke after a routine anesthetic and was treated with inhaled nitric oxide (INO). C1 Med Coll Georgia, Augusta, GA 30912 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Head, A (reprint author), Med Coll Georgia, 1120 15th St,BIW 2144, Augusta, GA 30912 USA. EM ahead@mcg.edu NR 21 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2006 VL 105 IS 3 BP 619 EP 621 DI 10.1097/00000542-200609000-00028 PG 3 WC Anesthesiology SC Anesthesiology GA 078OE UT WOS:000240112300026 PM 16931997 ER PT J AU Collins, SP Mielniczuk, LM Whittingham, HA Boseley, ME Schramm, DR Storrow, AB AF Collins, Sean P. Mielniczuk, Lisa M. Whittingham, Heather A. Boseley, Mark E. Schramm, David R. Storrow, Alan B. TI The use of noninvasive ventilation in emergency department patients with acute cardiogenic pulmonary edema: A systematic review SO ANNALS OF EMERGENCY MEDICINE LA English DT Review ID POSITIVE AIRWAY PRESSURE; CONGESTIVE-HEART-FAILURE; ACUTE RESPIRATORY-FAILURE; SUPPORT VENTILATION; RANDOMIZED-TRIAL; FACE MASK; OXYGEN-THERAPY; BILEVEL; METAANALYSES; PERFORMANCE AB Study objective: Acute cardiogenic pulmonary edema is a common cause of respiratory distress in emergency department (ED) patients. Noninvasive ventilation by noninvasive positive pressure ventilation or continuous positive airway pressure has been studied as a treatment strategy. We critically evaluate the evidence for the use of noninvasive ventilation on rates of hospital mortality and endotracheal intubation. Methods: We searched the databases of MEDLINE, EMBASE, and the Cochrane Library from 1980 to 2005. Additional sources included key journals, bibliographies of selected articles, and expert contact. We included studies that incorporated a randomized design; patients older than 18 years and with acute cardiogenic pulmonary edema; diagnosis and treatment initiated in the ED; noninvasive ventilation in addition to standard medical therapy compared to standard medical therapy alone, or noninvasive positive pressure ventilation compared to continuous positive airway pressure (both in addition to standard medical therapy); and data on hospital mortality or intubation. A random-effects model was used to obtain the summary risk ratios (RRs) and 95% confidence intervals (Cis) for hospital mortality and intubation. Results: A pooled analysis of 494 patients suggested that noninvasive ventilation in addition to standard medical therapy significantly reduced hospital mortality compared to standard medical therapy alone (RR 0.61; [95% Cl 0.41, 0.91]). Similarly, a meta-analysis of 436 patients suggested that noninvasive ventilation was associated with a significant decrease in intubation rates (RR 0.43; [95% Cl 0.21, 0.87]). Conclusion: Our results suggest that noninvasive ventilation with standard medical therapy is advantageous over standard medical therapy alone in ED patients with acute cardiogenic pulmonary edema. Future studies, powered appropriately for mortality and intubation rates, are necessary to confirm these findings. C1 Univ Cincinnati, Dept Emergency Med, Cincinnati, OH 45267 USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Univ Toronto, Univ Hlth Network, Div Pulm Crit Care, Toronto, ON, Canada. Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Univ Ottawa, Dept Otolaryngol, Ottawa, ON, Canada. Vanderbilt Univ, Dept Emergency Med, Nashville, TN USA. RP Collins, SP (reprint author), Univ Cincinnati, Dept Emergency Med, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM sean.collins@uc.edu NR 27 TC 73 Z9 79 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2006 VL 48 IS 3 BP 260 EP 269 DI 10.1016/j.annemergmed.2006.01.038 PG 10 WC Emergency Medicine SC Emergency Medicine GA 080OD UT WOS:000240256400007 PM 16934647 ER PT J AU Strehlow, MC Emond, SD Shapiro, NI Pelletier, AJ Camargo, CA AF Strehlow, Matthew C. Emond, Stephen D. Shapiro, Nathan I. Pelletier, Andrea J. Camargo, Carlos A., Jr. TI National study of emergency department visits for sepsis, 1992 to 2001 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT American-College-of-Emergency-Physicians Research Forum CY SEP-OCT -, 2005 CL Washington, DC SP Amer Coll Emergency Phys ID UNITED-STATES; EPIDEMIOLOGY; DEFINITIONS; GUIDELINES; INFECTION AB Study objective: Epidemiologic data on emergency department (ED) patients with sepsis are limited. Inpatient discharge records from 1979 to 2000 show that hospitalizations for sepsis are increasing. We examine the epidemiology of sepsis in US EDs and the hypothesis that sepsis visits are increasing. Methods: The National Hospital Ambulatory Medical Care Survey data (1992 to 2001) provided nationally representative estimates of frequency and disposition in adult ED visits for sepsis. Sepsis visits were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes; severe sepsis was defined as sepsis in conjunction with organ failure. Results: Of 712 million adult visits during the 10-year period, approximately 2.8 million (0.40%, 95% confidence interval [CI] 0.33% to 0.46%) were related to sepsis. We found no significant increase in overall ED visits for sepsis from 1992 to 2001 (P for trend=.09). ED patients with sepsis were more likely to be elderly, non-Hispanic, and publicly insured and to arrive by ambulance compared with nonsepsis patients (all P<.01). The overall admission rate was 87% (95% Cl 82% to 92%), with only 12% (95% Cl 8% to 16%) of patients admitted to the ICU. The most frequent codiagnoses were pneumonia (13%), urinary tract infection (13%), and dehydration (11%). Severe sepsis accounted for 8% (95% Cl 5% to 11%) of sepsis visits, for an annual incidence of 0.01%; 98% of patients with severe sepsis were admitted. Conclusion: In contrast to data from hospital discharges, ED visits for sepsis demonstrated no increase. Most ED visits for sepsis resulted in admission to non-critical care units. C1 Stanford Univ, Sch Med, Stanford Kaiser Emergency Med Residency Program, Palo Alto, CA 94304 USA. Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Strehlow, MC (reprint author), 701 Welch Rd Bldg C, Palo Alto, CA 94025 USA. EM strehlow@stanford.edu RI Shapiro, Nathan/F-1718-2016 NR 12 TC 81 Z9 84 U1 0 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2006 VL 48 IS 3 BP 326 EP 331 DI 10.1016/j.annemergmed.2006.05.003 PG 6 WC Emergency Medicine SC Emergency Medicine GA 080OD UT WOS:000240256400016 PM 16934654 ER PT J AU Clark, S Gaeta, TJ Kamarthi, GS Camargo, CA AF Clark, Sunday Gaeta, Theodore J. Kamarthi, Geeta S. Camargo, Carlos A. TI ICD-9-CM coding of emergency department visits for food and insect sting allergy SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE food allergy; insect sting allergy; International Classification of Diseases; Ninth Revision; Clinical Modification (ICD-9-CM) codes; emergency department ID MULTICENTER; ACCURACY; CLASSIFICATION; DISORDERS; DIAGNOSIS; CODES AB PURPOSE: Little is known about the role of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identification of specific allergic reactions in the emergency department (ED). METHODS: Investigators in 10 EDs reviewed 1395 charts of consecutive patients presenting with food allergy (ICD-9-CM codes 693.1 and 995.60 to 995.69) and insect sting allergy (code 989.5). They also reviewed charts of patients with "unspecified" allergic reactions (codes 995.0 [other anaphylactic shock] and 995.3 [allergy, unspecified]) to identify additional patients with food or insect sting allergy. RESULTS: Of 406 patients with food allergy, 216 patients (53%) were coded as food allergy, whereas the remaining 190 patients (47%) were not. Of 394 patients with insect sting allergy, 341 (87%) were coded as insect sting allergy, whereas 53 patients (13%) were not. Characteristics of ICD-9-CM-identified compared with chart-review-identified patients differed for both food and insect sting allergy. ICD-9-CM-identified patients with food allergy were less likely to experience anaphylaxis. CONCLUSIONS: Almost half the patients with food allergy would have been missed by using food-specific ICD-9-CM codes alone, whereas only 13% of patients with insect sting allergy would have been missed. Furthermore, characteristics of these allergy patients would have been biased by studying only patients identified by using the allergen-specific ICD-9-CM codes. C1 Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. New York Methodist Hosp, Dept Emergency Med, Brooklyn, NY USA. RP Clark, S (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM sclark3@partners.org FU NIAID NIH HHS [AI52338]; NIEHS NIH HHS [T32 ES07069] NR 10 TC 60 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2006 VL 16 IS 9 BP 696 EP 700 DI 10.1016/j.annepidem.2005.12.003 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 080MZ UT WOS:000240253300008 PM 16516491 ER PT J AU Dunn, JS Mlynarski, WM Pezzolesi, MG Borowiec, M Powers, C Krolewski, AS Doria, A AF Dunn, J. S. Mlynarski, W. M. Pezzolesi, M. G. Borowiec, M. Powers, C. Krolewski, A. S. Doria, A. TI Examination of PPP1R3B as a candidate gene for the type 2 diabetes and MODY loci on chromosome 8p23 SO ANNALS OF HUMAN GENETICS LA English DT Article DE type 2 diabetes; MODY; protein phosphatase ID GLYCOGEN-TARGETING SUBUNIT; SUSCEPTIBILITY LOCUS; PROTEIN PHOSPHATASE-1; INDEPENDENT REPLICATION; INSULIN-RESISTANCE; GENOMEWIDE SEARCH; SIB PAIRS; LINKAGE; POLYMORPHISM; MELLITUS AB The product of the PPP1R3B gene (G(L)) is the regulatory subunit of PP1 - a serine/threonine phosphatase involved in the modulation of glycogen synthesis in the liver and skeletal muscle. The PPP1R3B gene is located on chromosome 8p23 in a region that has been linked with type 2 diabetes and maturity-onset diabetes of the young (MODY). We examined whether sequence variants at the PPP1R3B locus are responsible for the linkage with diabetes observed at this location. RT-PCR analysis revealed the existence of two alternative promoters. These and the two exons of this gene were sequenced in the probands of 13 Joslin families showing the strongest evidence of linkage at 8p23. A total of 20 variants were observed: two in the 5' flanking region, one in the intron (9 bp 5' of exon 2), and 17 in the 3' UTR. The intronic variant generated a new acceptor splice site, resulting in an alternative splice variant with a longer 5' UTR. However, neither this nor other variants segregated with diabetes in the 13 'linked' families. Furthermore, allele frequencies were similar in 90 family probands from the Joslin Study and 347 unrelated controls. Thus, genetic variability in the PPP1R3B gene does not appear to contribute to diabetes in our mostly Caucasian families. However, a role cannot be excluded in other populations such as the Japanese, among whom linkage to diabetes is also observed at 8p23 and a non-synonymous mutation has been detected in the PPP1R3B gene. C1 Joslin Diabet Ctr, Sect Gent & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Med Univ Lodz, Dept Pediat, Lodz, Poland. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Gent & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu RI Borowiec, Maciej/S-9220-2016 FU NIDDK NIH HHS [DK-36836, DK-47475, DK-55523] NR 34 TC 9 Z9 9 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD SEP PY 2006 VL 70 BP 587 EP 593 DI 10.1111/j.1469-1809.2005.00248.x PN 5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 070JV UT WOS:000239518900004 PM 16907705 ER PT J AU Giantonio, BJ Levy, DE O'Dwyer, PJ Meropol, NJ Catalano, PJ Benson, AB AF Giantonio, B. J. Levy, D. E. O'Dwyer, P. J. Meropol, N. J. Catalano, P. J. Benson, A. B., III TI A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the eastern cooperative oncology group study E2200 SO ANNALS OF ONCOLOGY LA English DT Article DE first-line therapy; high-dose bevacizumab; IFL; metastatic colorectal cancer ID ENDOTHELIAL GROWTH-FACTOR; HUMANIZED MONOCLONAL-ANTIBODY; RANDOMIZED-TRIAL; 1ST-LINE TREATMENT; PLUS FLUOROURACIL; LIVER METASTASIS; COLON-CANCER; ANGIOGENESIS; OXALIPLATIN; EXPRESSION AB Aim: Patients with untreated advanced colorectal cancer were enrolled to this single arm phase II multi-center cooperative group trial of bevacizumab combined with IFL. The first 20 patients received irinotecan (125 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and leucovorin (20 mg/m(2)) weekly for four of six weeks and high-dose bevacizumab (10 mg/kg) every other week. Following a toxicity review of other trials using IFL, subsequent patients were enrolled at reduced doses of irinotecan (100 mg/m(2)) and 5-fluorouracil (400 mg/m(2)). Results: Of the 92 patients accrued to the study, toxicity data are available for 87 patients and efficacy data for 81 patients. At a median follow-up of 37.5 months, median overall survival is 26.3 months, median progression free survival is 10.7 months and 1-year survival is 85%. The overall response rate is 49.4% (6.2% complete responses). A reduction in the starting doses of irinotecan and 5-fluorouracil decreased the occurrence of vomiting, diarrhea and neutropenia related complications. Bleeding occurred in 37 patients; all events but two were grade 1 or grade 2. There were nine reports of grade 3 or grade 4 thrombo-embolic events. Hypertension of any grade occurred in 13% of patients and proteinuria was infrequent. Conclusion: High-dose bevacizumab added to IFL is a well-tolerated and highly active regimen in patients with previously untreated metastatic colorectal cancer. C1 Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Giantonio, BJ (reprint author), Univ Penn, 3400 Spruce St,12 Penn Tower, Philadelphia, PA 19104 USA. EM giantonio.bruce@jimmy.harvard.edu FU NCI NIH HHS [CA66636, CA27525, CA23318, CA17145, CA15488, CA21115] NR 27 TC 91 Z9 98 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2006 VL 17 IS 9 BP 1399 EP 1403 DI 10.1093/annonc/mdl161 PG 5 WC Oncology SC Oncology GA 085FC UT WOS:000240587900009 PM 16873427 ER PT J AU Zeitels, SM Akst, LM Burns, JA Hillman, RE Broadhurst, MS Anderson, RR AF Zeitels, Steven M. Akst, Lee M. Burns, James A. Hillman, Robert E. Broadhurst, Matthew S. Anderson, R. Rox TI Office-based 532-nm pulsed KTP laser treatment of glottal papillomatosis and dysplasia SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the American-Broncho-Esophagological-Association CY MAY 19-20, 2006 CL Chicago, IL SP Amer Broncho Esophagol Assoc DE dysphonia; dysplasia; glottis; hoarseness; keratosis; KTP laser; laryngoscopy; papillomatosis; vocal cord; vocal fold ID DYE-LASER AB Objectives: Treatment of glottal papillomatosis and dysplasia was mirror-guided and done in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. The primary treatment goals, which are disease regression and voice restoration and/or maintenance, are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. To obviate general anesthesia, office-based laser laryngeal surgery was first done in 2001 with the 585-nm pulsed dye laser (PDL), because it employs a fiber delivery system and its energy is selectively absorbed by oxyhemoglobin. Since then, this new angiolytic laser treatment paradigm has become a mainstay of management for many surgeons; however, there are a number of shortcomings of the PDL. To further develop this concept and address the limitations of the PDL, we used a 532-nm pulsed potassium titanyl phosphate (KTP) laser. Methods: A prospective assessment was performed on 48 patients in 72 cases of recurrent glottal dysplasia (36) or papillomatosis (36). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation. Results: Two dysplasia patients did not tolerate the procedure. Of the treatable dysplasia cases, there was follow-up in 29 of 34. Disease regression was at least 75% in 18 of 29 cases (62%), 50% to 75% in 7 of 29 (24%), and 25% to 50% in the remaining 4 of 29 (14%). Papilloma patients returned for treatment when symptoms recurred, so disease regression could not be assessed accurately. Similar to data obtained with the PDL, these data confirmed that dysplastic mucosa could normalize without resection. Conclusions: Our observations revealed that the 532-nm pulsed KTP laser provided enhanced performance over the PDL laser in a number of ways. The ability to use smaller glass fibers precluded mechanical trauma to the channels of the flexible laryngoscopes and allowed for improved suctioning of secretions. Oxyhemoglobin absorbs energy better at 532 nm than at 585 nm, and the KTP laser can be delivered through a longer pulse width. These factors provide enhanced hemostasis and improved intralesional energy absorbance. Finally, unlike the PDL, the KTP laser is a solid-state laser and is not prone to mechanical failure. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 13 TC 62 Z9 64 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2006 VL 115 IS 9 BP 679 EP 685 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 086KH UT WOS:000240671700005 PM 17044539 ER PT J AU Shrank, WH Asch, SM Joseph, GJ Young, HN Ettner, SL Kholodenko, Y Glassman, P Kravitz, RL AF Shrank, William H. Asch, Steven M. Joseph, George J. Young, Henry N. Ettner, Susan L. Kholodenko, Yelena Glassman, Peter Kravitz, Richard L. TI Physicians' perceived knowledge of and responsibility for managing patients' out-of-pocket costs for prescription drugs SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE out-of-pocket costs; pharmacy benefit design; prescription drugs ID PHARMACEUTICALS; INCENTIVES; ADHERENCE; CARE AB BACKGROUND: Most insurers in the US have implemented incentive-based formularies that rely on out-of-pocket costs to influence prescription drug utilization. Medicare Part D plans have broadly adopted such benefit designs. OBJECTIVE: To evaluate physicians' perceptions of their knowledge of formularies and out-of-pocket costs, factors that influence knowledge of costs, physicians' perceived responsibility for helping patients manage their out-of-pocket costs for prescription drugs, and physicians' perceptions of the role of pharmacists in managing these costs. METHODS: A multiple-choice survey was mailed to a random sample of 1200 physician members of the California Medical Association; a phone survey of nonresponders was then conducted. RESULTS: Of 1027 surveys delivered to correct addresses, 509 (49.6%) responses were received. Thirty-three percent of physicians reported that they were usually or always aware of patients' formularies and 20% were usually or always aware of patients' out-of-pocket costs for medications. Surgeons, emergency department physicians, and physicians that prescribe from more formularies than other physicians are less likely to be aware of patients' out-of-pocket costs, while physicians in large practices and those who use computers to prescribe are more aware. While 91% of physicians agreed that it is important that patients' out-of-pocket costs be managed, 40% somewhat or strongly agreed that it is their responsibility to help. Sixty-five percent of physicians believed that it is the responsibility of the pharmacist to be familiar with patients' out-of-pocket costs. CONCLUSIONS: Physicians often lack the knowledge to assist patients in the management of their out-of-pocket costs for prescription drugs and they depend on pharmacists to help patients manage those costs. Computer order entry and resources available in large physician organizations improve physicians' awareness of out-of-pocket costs when prescribing. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidmiol & Pharmacoecon, Boston, MA 02120 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. RAND Hlth, Div Gen Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Wisconsin, Sch Pharm, Social Adm Sci Div, Madison, WI 53706 USA. Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Hlth Serv, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Gen Internal Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA. Univ Calif Davis, Ctr Hlth Serv Res Primary Care, Sacramento, CA 95817 USA. RP Shrank, WH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidmiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. EM wshrank@partners.org OI Kravitz, Richard/0000-0001-5575-529X NR 25 TC 26 Z9 27 U1 1 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD SEP PY 2006 VL 40 IS 9 BP 1534 EP 1540 DI 10.1345/aph.1H158 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078OG UT WOS:000240112500005 PM 16912246 ER PT J AU Garcia, JA Driscoll, DN Donelan, MB AF Garcia, Jesus A. Driscoll, Daniel N. Donelan, Matthias B. TI Pursestring thigh lift - Direct approach for a problematic deformity SO ANNALS OF PLASTIC SURGERY LA English DT Article DE purse-string; closure; thigh lift ID PURSE-STRING SUTURE; SKIN DEFECTS; CLOSURE; RECONSTRUCTION; REDUCTION; EXCISION; SCAR AB Extreme thigh lipodystrophy localized in a "saddlebag" distribution can be difficult to treat with conventional body-lift approaches. We present a case of extreme thigh lipodystrophy treated with suction lipectomy and direct excision of skin and fat. The circular defects were closed with pursestring sutures and yielded a greatly improved contour and minimal iatrogenic deformity or scarring. In properly selected patients, the pursestring thigh-lift can provide a superior esthetic result. C1 Shriners Burn Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Donelan, MB (reprint author), Shriners Burn Hosp, Div Plast Surg, 51 Blossom St, Boston, MA 02114 USA. EM mdonelan@partners.org NR 14 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD SEP PY 2006 VL 57 IS 3 BP 330 EP 332 DI 10.1097/01.sap.0000216261.41085.29 PG 3 WC Surgery SC Surgery GA 077PT UT WOS:000240042800019 PM 16929204 ER PT J AU Kang, WD Gomez, FE Lan, JG Sano, Y Ueno, C Kudsk, KA AF Kang, Woodae Gomez, F. Enrique Lan, Jinggang Sano, Yoshifumi Ueno, Chikara Kudsk, Kenneth A. TI Parenteral nutrition impairs gut-associated lymphoid tissue and mucosal immunity by reducing lymphotoxin beta receptor expression SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 126th Annual Meeting of the American-Surgical-Association CY APR 20-22, 2006 CL Boston, MA SP Amer Surg Assoc ID UPPER RESPIRATORY-TRACT; MAJOR ABDOMINAL-TRAUMA; SEPTIC COMPLICATIONS; ENTERAL NUTRITION; ENHANCING DIET; IGA SYNTHESIS; ROUTE; CELLS; MORBIDITY; BENEFITS AB Objective: To determine the effects of parenteral nutrition (PN) on LT beta R in gut-associated lymphoid tissue (GALT), particularly the intestine and Peyer's patches (PP). Summary Background Data: Lack of enteral stimulation with PN impairs mucosal immunity and reduces IgA levels through depression of GALT cytokines (IL-4 and IL-10) and GALT specific adhesion molecules. We have shown that each is critical to intact mucosal immunity through effects on lymphocyte homing, IgA production, and resistance to antibacterial and antiviral immunity. IgA is the principal specific immunologic mucosal defense. LT beta R stimulation controls production of IL-4, the adhesion molecule MAdCAM-1, and other key components of GALT, all of which are important in increasing IgA levels and maintaining mucosal defenses. Methods: Experiment 1: LT beta R expression in intestine and PP was analyzed by Western blot after 5 days of chow, a complex enteral diet (CED), or PN. Diets were isocaloric and isonitrogenous except for chow. Experiment 2: After completing pilot experiments to determine the appropriate dose of the LT beta R agonistic antibody, mice received chow, PN + 5 mu g of anti-LT beta R mAb (2 times/d, i.v.) or PN + isotype control antibody. PP lymphocytes and intestinal IgA levels were measured after 2 days. Results: Lack of enteral stimulation with PN significantly decreased LT beta R expression in intestine and PP compared with chow and CED. LT beta R stimulation with an agonistic anti-LT beta R mAb significantly increased PP lymphocyte counts and intestinal IgA in PN fed-mice. Conclusions: LT beta R expression is critical for GALT control mechanisms and intact mucosal immunity. PN reduces LT beta R expression, PP lymphocytes, and intestinal IgA production. Exogenous LT beta R stimulation reverses PN-induced depression of gut mucosal immunity. C1 Univ Wisconsin, Coll Med & Publ Hlth, Dept Surg, Madison, WI USA. 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, R01 GM53439-06A1] NR 30 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2006 VL 244 IS 3 BP 392 EP 399 DI 10.1097/01.sla.0000234797.42935.46 PG 8 WC Surgery SC Surgery GA 080QB UT WOS:000240261500007 PM 16926565 ER PT J AU Brewster, DC Jones, JE Chung, TK Lamuraglia, GM Kwolek, CJ Watkins, MT Hodgman, TM Cambria, RP AF Brewster, David C. Jones, John E. Chung, Thomas K. Lamuraglia, Glenn M. Kwolek, Christopher J. Watkins, Michael T. Hodgman, Thomas M. Cambria, Richard P. TI Long-term outcomes after endovascular abdominal aortic aneurysm repair - The first decade SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 126th Annual Meeting of the American-Surgical-Association CY APR 20-22, 2006 CL Boston, MA SP Amer Surg Assoc ID RANDOMIZED CONTROLLED-TRIAL; OPEN SURGICAL REPAIR; LIFE-TABLE ANALYSIS; CLINICAL-TRIAL; STENT-GRAFT; EUROSTAR EXPERIENCE; SECONDARY INTERVENTIONS; INITIAL-EXPERIENCE; ENDOLUMINAL REPAIR; FOLLOW-UP AB Objective: The proper role of endovascular abdominal aortic aneurysm repair (EVAR) remains controversial, largely due to uncertain late results. We reviewed a 12-year experience with EVAR to document late outcomes. Methods: During the interval January 7, 1994 through December 31, 2005, 873 patients underwent EVAR utilizing 10 different stent graft devices. Primary outcomes examined included operative mortality, aneurysm rupture, aneurysm-related mortality, open surgical conversion, and late survival rates. The incidence of endoleak, migration, aneurysm enlargement, and graft patency was also determined. Finally, the need for reintervention and success of such secondary procedures were evaluated. Kaplan-Meier and multivariate methodology were used for analysis. Results: Mean patient age was 75.7 years (range, 49-99 years); 81.4% were male. Mean follow-up was 27 months; 39.3% of patients had 2 or more major comorbidities, and 19.5% would be categorized as unfit for open repair. On an intent-to-treat basis, device deployment was successful in 99.3%. Thirty-day mortality was 1.8%. By Kaplan-Meier analysis, freedom from AAA rupture was 97.6% at 5 years and 94% at 9 years. Significant risk factors for late AAA rupture included female gender (odds ratio OR, 6.9; P = 0.004) and device-related endoleak (OR, 16.06; P = 0.009). Aneurysm-related death was avoided in 96.1% of patients, with the need for any reintervention (OR, 5.7 P = 0.006), family history of aneurysmal disease (OR, 9.5; P = 0.075), and renal insufficiency (OR, 7.1; P = 0.003) among its most important predictors. 87 (10%) patients required reintervention, with 92% of such procedures being catheter-based and a success rate of 84%. Significant predictors of reintervention included use of first-generation devices (OR, 1.2; P < 0.01) and late onset endoleak (OR, 64; P < 0.001). Current generation stent grafts correlated with significantly improved outcomes. Cumulative freedom from conversion to open repair was 93.3% at 5 through 9 years, with the need for prior reintervention (OR, 16.7; P = 0.001) its most important predictor. Cumulative survival was 52% at 5 years. Conclusions: EVAR using contemporary devices is a safe, effective, and durable method to prevent AAA rupture and aneurysm-related death. Assuming suitable AAA anatomy, these data justify a broad application of EVAR across a wide spectrum of patients. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brewster, DC (reprint author), Massachusetts Gen Hosp, 1 Hawthorne Pl, Boston, MA 02114 USA. EM dcbrewster@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 64 TC 146 Z9 150 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2006 VL 244 IS 3 BP 426 EP 438 DI 10.1097/01.sla.0000234893.88045.dc PG 13 WC Surgery SC Surgery GA 080QB UT WOS:000240261500011 PM 16926569 ER PT J AU Finckh, A Choi, HK Wolfe, F AF Finckh, A. Choi, H. K. Wolfe, F. TI Progression of radiographic joint damage in different eras: trends towards milder disease in rheumatoid arthritis are attributable to improved treatment SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID BECOMING LESS SEVERE; LONG-TERM OUTCOMES; PROPENSITY SCORE; CLINICAL-TRIALS; RADIOLOGICAL PROGRESSION; INCLUSION CRITERIA; DISABILITY; MORTALITY; CARE; PREDICTORS AB Background: Severity of rheumatoid arthritis and progression of radiographic joint damage have decreased over the last decades. Aim: To examine whether this trend is attributable to an underlying trend towards milder disease or to improved treatment. Methods: The study used an inception cohort of patients with early rheumatoid arthritis seen at the Wichita Arthritis Center, Wichita, Kansas, USA, since 1973 and monitored prospectively since their first clinic visit through clinical, radiographic, laboratory, demographic and self-reported data. The radiographic disease progression in patients with disease onset in the 1970s, 1980s and 1990s was compared using a multivariate regression model for longitudinal data. The analysis was adjusted for differences in baseline predictors, type of disease-modifying antirheumatic drugs (DMARDs) and steroid use. Results: 418 patients with rheumatoid arthritis with radiographic follow-up were included. Patients in earlier decades used fewer DMARDs, had longer disease durations and higher tender joint counts at their first visit. Other important predictors of disease progression did not differ significantly between decades of disease onset. The unadjusted rates of radiographic progression differed between decades (analysis of variance, p = 0.01), with a significant trend towards less radiographic progression in more recent times (trend, p < 0.001). However, after adjusting for DMARD use, steroid use and baseline predictors, differences between decades vanished (analysis of variance, p = 0.40) and the trend towards less radiographic progression disappeared (trend, p = 0.45). Conclusion: These results suggest that the observed trend towards milder disease in rheumatoid arthritis is attributable to more effective antirheumatic treatment and not to a secular trend. C1 Univ Geneva, Div Rheumatol, CH-1211 Geneva 14, Switzerland. Massachusetts Gen Hosp, Dept Med, Arthrit Unit, Boston, MA 02114 USA. Univ Kansas, Sch Med, Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA. RP Finckh, A (reprint author), Univ Geneva, Div Rheumatol, Av Beau Sejour 26, CH-1211 Geneva 14, Switzerland. EM afinckh@post.harvard.edu OI Finckh, Axel/0000-0002-1210-4347 NR 45 TC 62 Z9 63 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD SEP PY 2006 VL 65 IS 9 BP 1192 EP 1197 DI 10.1136/ard.2005.049338 PG 6 WC Rheumatology SC Rheumatology GA 073DI UT WOS:000239722600014 PM 16540549 ER PT J AU Mitsiades, CS Bogdanos, J Karamanolakis, D Milathianakis, C Dimopoulos, T Koutsilieris, M AF Mitsiades, Constantine S. Bogdanos, John Karamanolakis, Dimitrios Milathianakis, Constantine Dimopoulos, Theodoros Koutsilieris, Michael TI Randomized controlled clinical trial of a combination of somatostatin analog and dexamethasone plus zoledronate vs. zoledronate in patients with androgen ablation-refractory prostate cancer SO ANTICANCER RESEARCH LA English DT Article DE prostate cancer; androgen ablation-refractory; osteoblastic metastasis; somatostatin analog; dexamethasone; zoledronate ID GLUCOCORTICOID RECEPTOR FUNCTION; TUMOR-CELL-INTERACTIONS; GROWTH-FACTORS; PERIPHERAL-BLOOD; BONE METASTASES; LHRH ANALOG; PHASE-II; THERAPY; CHEMOTHERAPY; CARCINOMA AB Background: As previously shown, the combination of standard androgen ablation therapy with somatostatin analog and dexamethasone in metastatic androgen ablation-refractory (stage D-3) prostate cancer (PrCa) patients has a favorable profile of side-effects., durable objective antitumor activity (up to 60% partial response rate) and palliative effects. Bisphosphonates interfere with bone remodeling at the sites of PrCa bone metastases and have been postulated to have indirect and/or direct anti-PrCa activity. Materials and Methods: A randomized controlled clinical trial was conducted to compare a combination of somatostatin analog (octreotide 20 mg i.m. every 28 days) and oral dexamethasone (4 mg daily for I month, gradually reduced to 1 mg daily by the fourth month, with a I mg daily maintenance dose thereafter) plus zoledronate (4 mg i.v. every 4 weeks) vs. zoledronate only. All patients in both arms remained in basic androgen blockade throughout the study. Results: Thirty-eight stage D3 patients (mean age 72.8 +/- 6.8 years) were randomized to either treatment ann of the study. The trial was stopped after a pre-specified interim analysis met the criteria for early closure., i.e. significant difference in outcomes between the two treatment arms. Partial responses (PR, >= 50% PSA decline) were observed in 13 out of 20 patients with combination therapy vs. none with zoledronate. Tire combination therapy arm had signiflcantly better outcome with respect to median progression-free survival (7.0 vs. 1.0 months, p < 0.0001), median overall survival (OS) (12.0 vs. 9.0 months, p = 0.0027), median PrCa-specific OS (defined as time from onset of therapy until PrCa-related death) (16 vs. 9.0 months, p=0.0005) and median duration of bone pain improvement (> 14 vs. 4 months p=0.00001 by log-rank tests). Conclusion: For androgen ablation-refractory metastatic PrCa patients under androgen ablation, the combination of dexamethasone, somatostatin analog and zoledronate offered superior objective and palliative clinical responses than zoledronate alone. C1 Univ Athens, Sch Med, Dept Expt Physiol, GR-11527 Athens, Greece. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. METAXA Anticanc Hosp, Urol Clin, Piraeus, Greece. PANAGIA Gen Hosp, Urol Clin, Thessaloniki, Greece. RP Koutsilieris, M (reprint author), Univ Athens, Sch Med, Dept Expt Physiol, 75 Micras Asias St, GR-11527 Athens, Greece. EM mkouts@medscape.com NR 39 TC 25 Z9 28 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2006 VL 26 IS 5B BP 3693 EP 3700 PG 8 WC Oncology SC Oncology GA 100ZA UT WOS:000241707500012 PM 17094387 ER PT J AU Pumbwe, L Glass, D Wexler, HM AF Pumbwe, Lilian Glass, Daniel Wexler, Hannah M. TI Efflux pump overexpression in multiple-antibiotic-resistant mutants of Bacteroides fragilis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FLUOROQUINOLONE RESISTANCE; ANTIMICROBIAL RESISTANCE; SELECTION WINDOW; ACTIVE EFFLUX; BACTERIA; MUTATIONS AB Multidrug-resistant mutants of a wild-type Bacteroides fragilis strain (strain ADB77) and a quadruple resistance nodulation division family efflux pump deletion mutant (ADB77 Delta bmeB1 Delta bmeB3 Delta bmeB12 Delta bmeB15) were selected with antimicrobials. Ampicillin, doripenem, imipenem, levofloxacin, and metronidazole selected for mutants from both strains; cefoxitin selected for mutants from strain ADB77 only; and sodium dodecyl sulfate selected mutants from ADB77 Delta bmeB1 Delta bmeB3 Delta bmeB12 Delta bmeB15 only. The mutants overexpressed one or more efflux pumps. C1 Univ Calif Los Angeles, Sch Med, Wadsworth Anaerobe Lab, Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Wexler, HM (reprint author), Univ Calif Los Angeles, Sch Med, Wadsworth Anaerobe Lab, Greater Los Angeles Vet Adm Healthcare Syst, Bldg 304,Room E3-224,GLAVAHCS 691-151J, Los Angeles, CA 90073 USA. EM hwexler@ucla.edu NR 16 TC 24 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2006 VL 50 IS 9 BP 3150 EP 3153 DI 10.1128/AAC.00141-06 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 081DI UT WOS:000240297000036 PM 16940115 ER PT J AU Block, K Rcono, JM Lee, DY Bhandari, B Choudhury, GG Abboud, HE Gorin, Y AF Block, Karen Rcono, Jill M. Lee, Duck-Yoon Bhandari, Basant Choudhury, Goutam Ghosh Abboud, Hanna E. Gorin, Yves TI Arachidonic acid-dependent activation of a p22(phox)-based NAD(P)H oxidase mediates angiotensin II-induced mesangial cell protein synthesis and fibronectin expression via Akt/PKB SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID SMOOTH-MUSCLE-CELLS; AKT/PROTEIN KINASE-B; NADPH OXIDASE; MESSENGER-RNA; DIABETIC-NEPHROPATHY; NOX FAMILY; HYPERTROPHY; MECHANISMS; PATHWAYS; GROWTH AB Angiotensin 11 (Ang 11) induces protein synthesis and hypertrophy through arachidonic acid (AA)- and redox-dependent activation of the serine-threonine kinase Akt/PKB in mesangial cells (MCs). The role of NAD(P)H oxidase component p22(phox) was explored in this signaling pathway and in Ang II-induced expression of the extracellular matrix protein fibronectin. Ang 11 causes activation of Akt/PKB and induces fibronectin protein expression, effects abrogated by phospholipase A 2 inhibition and mimicked by AA. Ang 11 and AA also elicited an increase in fibronectin expression that was reduced with a dominant negative mutant of Akt/PKB. Exposure of the cells to hydrogen peroxide stimulates Akt/PKB activity and fibronectin synthesis. The antioxidant N-acetylcysteine abolished Ang II- and AA-induced Akt/PKB activation and fibronectin expression. Western blot analysis revealed high levels of p22(phox) in MCs. Antisense (AS) but not sense oligonucleotides for p22(phox) prevented ROS generation in response to Ang 11 and AA. AS p22(phox) inhibited Ang II- or AA-induced Akt/PKB as well as protein synthesis and fibronectin expression. These data provide the first evidence, in MCs, of activation by AA of a p22(phox)-based NAD(P)H oxidase and subsequent generation of ROS. Moreover, this pathway mediates the effect of Ang 11 on Akt/PKB-induced protein synthesis and fibronectin expression. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol MC 7882, San Antonio, TX 78229 USA. Audie L Murphy Mem Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Gorin, Y (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol MC 7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gorin@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU NIDDK NIH HHS [P50 DK 61597, DK 55815, DK 33665, DK 50190, DK 43988] NR 43 TC 28 Z9 28 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD SEP-OCT PY 2006 VL 8 IS 9-10 BP 1497 EP 1508 DI 10.1089/ars.2006.8.1497 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 084HL UT WOS:000240523900008 PM 16987006 ER PT J AU Caplan, D Dede, G Michaud, J AF Caplan, David Dede, Gayle Michaud, Jennifer TI Task-independent and task-specific syntactic deficits in aphasic comprehension SO APHASIOLOGY LA English DT Article ID SENTENCE COMPREHENSION; LANGUAGE COMPREHENSION AB We present 42 case studies of aphasic syntactic comprehension performances in sentence - picture matching and object manipulation, examining the data for the existence of deficits referable to particular syntactic structures, or such structures in a single sentence form, in both tasks. No deficits affected performance on all sentence types that contained a particular structure in both tasks. Most deficits affected single sentence forms in only one task, and no isolated deficits occurred. The implications of the pattern of performance for the nature of aphasic deficits are discussed. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, 175 Cambridge St,Suite 340,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org NR 13 TC 20 Z9 20 U1 0 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD SEP-NOV PY 2006 VL 20 IS 9-11 BP 893 EP 920 DI 10.1080/02687030600739273 PG 28 WC Clinical Neurology SC Neurosciences & Neurology GA 077MP UT WOS:000240033800005 ER PT J AU Lewis, D Goldztein, H Deschler, D AF Lewis, David Goldztein, Hernan Deschler, Daniel TI Use of hyperbaric oxygen to enhance auricular composite graft survival in the rabbit model SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID NO-REFLOW PHENOMENON; MYOCARDIAL-ISCHEMIA; REPERFUSION INJURY; THERAPY; RECONSTRUCTION; MICROCIRCULATION; GRANULOCYTES; INHIBITION; RATS; DOG AB Objective: To evaluate the efficacy of using hyperbaric oxygen to enhance auricular composite graft survival via a prospective, randomized, placebo-controlled, double-blind study. Design: Eighteen New Zealand White rabbits were randomly assigned to treatment (n=9) and control (n=9) groups after amputation and reattachment of 20 x 10-mm auricular composite grafts. The treatment group received twice-daily hyperbaric oxygen treatments for 5 days. The control group received twice-daily hyperbaric room-air treatments for 5 days. After 21 days, digital photographs of the composite grafts were taken and compared with photographs taken on the day of surgery. From these photographs, digital imaging software was used to calculate the percentage of graft survival. Results: The treated group ( 18 ears) had a mean +/- SD graft survival area of 80.67% +/- 19%, whereas the control group (18 ears) had a mean +/- SD graft survival area of 26.33% +/- 29%. Variance analysis with the Snedecor test allowed the comparison of the groups. The paired, 2-tailed t test proved a significant difference ( P <. 001) between groups. Conclusion: Hyperbaric oxygen therapy is an effective way to enhance the survival of 2-cm auricular composite grafts. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Div Head & Neck Surg Oncol, Boston, MA 02114 USA. RP Deschler, D (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Div Head & Neck Surg Oncol, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu NR 34 TC 6 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD SEP-OCT PY 2006 VL 8 IS 5 BP 310 EP 313 DI 10.1001/archfaci.8.5.310 PG 4 WC Surgery SC Surgery GA 085GY UT WOS:000240593300004 PM 16982986 ER PT J AU Murray, TG Sobrin, L AF Murray, Timothy G. Sobrin, Lucia TI The case for observational management of suspected small choroidal melanoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID COLLABORATIVE OCULAR MELANOMA; INITIAL MORTALITY FINDINGS; COMS RANDOMIZED-TRIAL; THICKNESS C1 Univ Miami, Ocular Oncol Serv, Bascom Palmer Eye Inst, Sch Med, Miami, FL 33136 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Murray, TG (reprint author), Univ Miami, Ocular Oncol Serv, Bascom Palmer Eye Inst, Sch Med, 90 NW 17th St, Miami, FL 33136 USA. EM tmurray@med.miami.edu NR 18 TC 10 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2006 VL 124 IS 9 BP 1342 EP 1344 DI 10.1001/archopht.124.9.1342 PG 3 WC Ophthalmology SC Ophthalmology GA 083DD UT WOS:000240435200018 PM 16966633 ER PT J AU Melanson, SEF Laposata, M Camargo, CA Chen, AA Tung, R Krauser, D Anwaruddin, S Baggish, A Cameron, R Sluss, P Lewandrowski, KB Lee-Lewandrowski, E Januzzi, JL AF Melanson, Stacy E. F. Laposata, Michael Camargo, Carlos A., Jr. Chen, Annabel A. Tung, Roderick Krauser, Dan Anwaruddin, Saif Baggish, Aaron Cameron, Renee Sluss, Patrick Lewandrowski, Kent B. Lee-Lewandrowski, Elizabeth Januzzi, James L. TI Combination of D-dimer and amino-terminal pro-B-type natriuretic peptide testing for the evaluation of dyspneic patients with and without acute pulmonary embolism SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DEEP VENOUS THROMBOSIS; CLINICAL PROBABILITY; DIAGNOSIS; EXCLUSION; EMERGENCY AB Context.-D-dimer concentration can be used to exclude a diagnosis of acute pulmonary embolism. However, clinicians frequently order unnecessary supplemental testing in patients with low concentrations of D-dimer. Elevations in natriuretic peptides have also been described in the setting of pulmonary embolism. Objective.-We investigated the integrative role of D-dimer with amino-terminal pro-B-type natriuretic peptide for the evaluation of patients with and without acute pulmonary embolism. Design.-Patients were selected for analysis from a previous study in which levels of D-dimer and amino-terminal pro-B-type natriuretic peptide were measured. The presence of pulmonary embolism was determined by computed tomographic angiography. Results.-The median levels of D-dimer were significantly higher in patients with acute pulmonary embolism. Similarly, the median levels of amino-terminal pro-B-type natriuretic peptide were higher in patients with pulmonary embolism. Conclusions.-The Roche Tina-quant D-Dimer immuno-turbidimetric assay provides a high negative predictive value and can be used to exclude acute pulmonary embolism in patients with dyspnea. Measurement of amino-terminal pro-B-type natriuretic peptide in addition to D-dimer improves specificity for acute pulmonary embolism without sacrificing negative predictive value. A combination of both markers may offer reassurance for excluding acute pulmonary embolism, and thus avoid redundant, expensive confirmatory tests. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Physiol, Div Clin Labs, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5894,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 17 TC 9 Z9 9 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2006 VL 130 IS 9 BP 1326 EP 1329 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 084IZ UT WOS:000240527900015 PM 16948519 ER PT J AU Patel, S Ho, JT Kumar, R Lai, K Ahangar, B Burgar, CG Scremin, AE AF Patel, Sheila Ho, Jeffrey T. Kumar, Rajeswari Lai, Khang Ahangar, Brian Burgar, Charles G. Scremin, Antonia E. TI Changes in motoneuron excitability in hemiplegic subjects after passive exercise when using a robotic arm SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Academy-of-Physical-Medicine-and-Rehabilitation CY OCT, 2004 CL Phoenix, AZ SP Amer Acad Phys Med & Rehabil DE cerebrovascular accident; H-reflex; rehabilitation; robotics ID MOTOR EVOKED-POTENTIALS; H-REFLEX; HOFFMANN REFLEX; SPASTICITY; HUMANS; STROKE AB Objective: To test the hypothesis that motoneuron excitability in stroke subjects is influenced by peripheral sensory input through passive exercise to the hemiplegic upper extremity. Design: Case-control prospective study. Setting: Physical medicine and rehabilitation inpatient and outpatient clinic at a tertiary Veterans Affairs medical center. Participants: Nineteen hemiplegic adult subjects with a history of a cerebrovascular event. Intervention: A standardized passive exercise program was performed on the right upper extremity by using a robotic arm. Nerve conduction study of the median nerve was obtained before and after the exercise. Maximum onset and peak amplitudes of the Hoffmann reflex (Hmax) and motor response (Mmax) wave were recorded. Main Outcome Measures: Hmax, Mmax, and Hmax/Mmax ratio. Results: Immediately after passive exercise, there was no significant alteration in the Hmax (P=.94), Mmax (P=.60), or Hmax/Mmax ratio (P=.53) as compared with pre-exercise evoked responses. Conclusions: Peripheral proprioceptive input with passive exercise does not cause appreciable change in the Hmax/Mmax ratio, suggesting that motoneuron excitability of the affected upper extremity in stroke subjects is not influenced by passive robotic intervention. C1 Univ Calif Los Angeles, Dept Phys Med & Rehabil, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Cent Texas Vet Hlth Care Syst, Temple, TX USA. RP Scremin, AE (reprint author), Univ Calif Los Angeles, Dept Phys Med & Rehabil, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 500,Mailcode 117, Los Angeles, CA 90073 USA. EM Antonio.Scremin@va.gov NR 24 TC 3 Z9 3 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2006 VL 87 IS 9 BP 1257 EP 1261 DI 10.1016/j.apmr.2006.05.026 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 082SO UT WOS:000240407700016 PM 16935064 ER PT J AU Jobe, BA Kim, CY Minjarez, RC O'Rourke, R Chang, EY Hunter, JG AF Jobe, Blair A. Kim, Charles Y. Minjarez, Renee C. O'Rourke, Robert Chang, Eugene Y. Hunter, John G. TI Simplifying minimally invasive transhiatal esophagectomy with the inversion approach - Lessons learned from the first 20 cases SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 17-20, 2006 CL San Francisco, CA SP Pacific Coast Surg Assoc ID PYLOROPLASTY; ANASTOMOSIS; CANCER; LEAK AB Hypothesis: The laparoscopic transhiatal esophagectomy can be simplified and performed safely and effectively by using a novel esophageal inversion technique. Design: Case series describing technique, initial experience, and learning curve with laparoscopic inversion esophagectomy. Setting: Tertiary care university hospital and veteran's hospital. Patients: Twenty consecutive patients with high-grade dysplasia (n = 16) and esophageal adenocarcinoma (n=4). Intervention: Laparoscopic inversion esophagectomy, a totally laparoscopic approach to transhiatal esophagectomy that incorporates distal to proximal inversion to improve mediastinal exposure and ease of dissection. Main Outcome Measures: Perioperative end points and complications, compared between the first and second groups of 10 patients. Results: There were 19 men and 1 woman. Median operative time was 448 minutes. Median blood loss was 175 cull. Median intensive care unit stay was 4 days, and median total hospital stay was 9 days. Overall anastomotic leak rate was 20%. Five patients developed an anastomotic stricture, all successfully managed with endoscopic dilation. There were 2 recurrent laryngeal nerve injuries, which resolved. There was no intraoperative or 30-day mortality. Between the first 10 consecutive cases and last 10 procedures, the incidence of anastomotic leak and stricture formation decreased from 30% to 10% and 40% to 10%, respectively. During this period, the number of lymph nodes harvested increased 9-fold, and duration of intensive care unit stay decreased from 8.00 to 2.50 days. Conclusions: Laparoscopic inversion esophagectomy is a safe procedure. The learning curve for the inversion approach is approximately 10 operations in the hands of esophageal surgeons with advanced laparoscopic expertise. C1 Oregon Hlth & Sci Univ, Dept Surg, Portland, OR USA. Portland VA Med Ctr, Surg Serv, Portland, OR USA. RP Jobe, BA (reprint author), Vet Adm Med Ctr, Surg Serv P3GS, POB 1034, Portland, OR 97207 USA. EM jobeb@ohsu.edu FU NIDDK NIH HHS [K23 DK066165-01] NR 15 TC 26 Z9 26 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 2006 VL 141 IS 9 BP 857 EP 865 DI 10.1001/archsurg.141.9.857 PG 9 WC Surgery SC Surgery GA 081XN UT WOS:000240351000003 PM 16983029 ER PT J AU Bartels, CM Bell, CL Bridges, AJ Shinki, K AF Bartels, Christie M. Bell, Carolyn L. Bridges, Alan J. Shinki, Kazuhiko TI Declining rates of serious extra-articular RA among US veteran inpatients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Wisconsin, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S208 EP S208 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200466 ER PT J AU Brey, RL Naqibuddin, M Holliday, SL Padilla, PA Fox, PT Narayana, S Franklin, C Samerdro, M Wallace, DJ Weissman, MH Petri, M AF Brey, Robin L. Naqibuddin, Mohammad Holliday, Stephen L. Padilla, Patricia A. Fox, Peter T. Narayana, Shalini Franklin, Crystal Samerdro, Margaret Wallace, Daniel J. Weissman, Michael H. Petri, Michelle TI Matrix metalloproteinase-9 (MMP-9) level, brain imaging findings and cognitive dysfunction in an SLE inception cohort: Brain CONECTIONS. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UTHSCSA, San Antonio, TX USA. Johns Hopkins Univ, Baltimore, MD USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S552 EP S552 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203048 ER PT J AU Collier, DS Grant, RW Estey, G Surrao, D Kay, J AF Collier, Deborah S. Grant, Richard W. Estey, Greg Surrao, Dominic Kay, Jonathan TI Outpatient rheumatologic care is facilitated and improved by an integrated informatics-based application. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S801 EP S801 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204323 ER PT J AU Collier, DS Kay, J Estey, G Surrao, D Grant, RW AF Collier, Deborah S. Kay, Jonathan Estey, Greg Surrao, Dominic Grant, Richard W. TI An electronic medical record-based DAS28 calculator improves office-based care of rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S801 EP S801 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204322 ER PT J AU Diaz-Torne, C Schumacher, HR Gomez-Vaquero, C Yu, XX Chen, LX Clayburne, G Einhorn, E Pessler, F AF Diaz-Torne, Cesar Schumacher, H. Ralph Gomez-Vaquero, C. Yu, Xiao-Xia Chen, Lan X. Clayburne, Gilda Einhorn, Eugene Pessler, Frank TI Absence of inflammation in synovial biopsies from patients with "Gulf War Syndrome" and joint pain. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Bellvitge Hosp, Barcelona, Spain. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 2 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 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S121 EP S122 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200230 ER PT J AU Firooz, N Taylor, CE Nouvong, A Masih, S Yentes, JM Perell, KL Fang, MA AF Firooz, Nazanin Taylor, Connie E. Nouvong, Aksone Masih, Sulabha Yentes, Jennifer M. Perell, Karen L. Fang, Meika A. TI Effects of footwear on medial knee osteoarthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Calif State Univ Fullerton, Fullerton, CA 92634 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S670 EP S670 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203391 ER PT J AU Hughes, LB Moreland, LW Howard, G Alarcon, GS Allison, DB Westfall, AO Conn, DL Jonas, BL Callahan, LF Smith, EA Gilkeson, GS Fraser, P Reich, D Bridges, SL AF Hughes, Laura B. Moreland, Larrt W. Howard, George Alarcon, Graciela S. Allison, David B. Westfall, Andrew O. Conn, Doyt L. Jonas, Beth L. Callahan, Leigh F. Smith, Edwin A. Gilkeson, Gary S. Fraser, Pat Reich, David Bridges, S. Louis, Jr. TI The HLA DRB1 shared epitope is associated with rheumatoid arthritis in African-Americans and correlates with higher estimated admixture of European ancestry: Results from the CLEAR registry. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Alabama, Birmingham, AL USA. Emory Univ, Atlanta, GA 30322 USA. Univ N Carolina, Chapel Hill, NC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. MIT, Broad Inst, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S392 EP S392 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202036 ER PT J AU Kannian, P Glickstein, LJ Drouin, EE Kwok, WW Nepom, GT Steere, AC AF Kannian, Priya Glickstein, Lisa J. Drouin, Elise E. Kwok, William W. Nepom, Gerald T. Steere, Allen C. TI Frequencies of Borrelia burgdorferi OspA(161-175)-specific T cells in HLA-DRB1*0401-positive patients with Lyme rthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Benaroya Res Inst, Seattle, WA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S546 EP S547 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203036 ER PT J AU Kay, J Matteson, EL Dasgupta, B Nash, P Durez, P Hall, S Hsia, EC Chiruvolu, P Han, J Rahman, MU AF Kay, J. Matteson, E. L. Dasgupta, B. Nash, P. Durez, P. Hall, S. Hsia, E. C. Chiruvolu, P. Han, J. Rahman, M. U. TI One-year results of golimumab compared with placebo in patients with active RA despite treatment with methotrexate: A phase II, randomized, double-blind, placebo-controlled, dose-ranging trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Coll Med, Rochester, MN USA. Sixth Ave Specialist Ctr, Cotton Tree, Australia. Clin Univ St Luc, St Luc, Belgium. Cabrini Med Ctr, Melbourne, Vic, Australia. Centocor R&D Inc, Malvern, PA USA. NR 0 TC 5 Z9 6 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S833 EP S833 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877204405 ER PT J AU Matzkies, FG Daikh, DI AF Matzkies, Franziska G. Daikh, David I. TI Development of lupus nephritis and IgG autoantibodies in NZB/W lupus prone mice is dependent on T-bet. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S283 EP S283 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201172 ER PT J AU Naqibuddin, M Carson, KA Sampedro, MM Wallace, DJ Weisman, MH Brey, RL Holliday, SL Narayana, S Fox, PT Franklin, C Padilla, PA Petri, M AF Naqibuddin, Mohammad Carson, Kathryn A. Sampedro, Margaret M. Wallace, Daniel J. Weisman, Michael H. Brey, Robin L. Holliday, Stephen L. Narayana, Shalini Fox, Peter T. Franklin, Crystal Padilla, Patricia A. Petri, Michelle TI Brain imaging (MRI and FDG-PET) and cognitive function in newly diagnosed SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S623 EP S623 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203256 ER PT J AU Naqibuddin, M Carson, KA Sampedro, MM Brey, RL Holliday, SL Narayana, S Fox, PT Franklin, C Padilla, PA Petri, M AF Naqibuddin, Mohammad Carson, Kathryn A. Sampedro, Margaret M. Brey, Robin L. Holliday, Stephen L. Narayana, Shalini Fox, Peter T. Franklin, Crystal Padilla, Patricia A. Petri, Michelle TI Anti-ds DNA and antiphospholipid antibodies are associated with abnormal brain MRI in newly diagnosed SLE patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S554 EP S554 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203053 ER PT J AU Pessler, F Diaz-Tome, C Dai, L Gomez-Vaquero, C Yu, XX Ralph Schumacher, H AF Pessler, Frank Diaz-Tome, Cesar Dai, Lie Gomez-Vaquero, C. Yu, Xiao-Xia Ralph Schumacher, H. TI How inflamed are "Non-Inflamed" surgical synovia? A quantitative immunohistochemical analysis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Bellvitge Hosp, Barcelona, Spain. Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou, Guangdong, Peoples R China. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S568 EP S568 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203095 ER PT J AU Pessler, F Gay, S Pandolfi, PP Schumacher, HR AF Pessler, Frank Gay, Steffen Pandolfi, Pier-Paolo Schumacher, H. Ralph TI Immunohistochemical localization of the proto-oncogene product FBI-1 (ZBTB7) in RA synovium and pannus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Zurich, Zurich, Switzerland. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S219 EP S219 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201001 ER PT J AU Pessler, F Dai, L Diaz-Torne, C Menetski, J Lu, M Schumacher, HR AF Pessler, Frank Dai, Lie Diaz-Torne, Cesar Menetski, Joseph Lu, Min Schumacher, H. Ralph TI Widespread expression of the zinc finger transcription factor Egr-1 in RA Synovium. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Sun Yat Sen Univ, Hosp 2, Guangzhou, Peoples R China. Bellvitge Hosp, Barcelona, Spain. Merck Res Labs, Rahway, NJ USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S219 EP S219 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201002 ER PT J AU Scalapino, KJ Daikh, DI AF Scalapino, Kenneth J. Daikh, David I. TI Suppression of lupus glomerulonephritis by exogenously expanded regulatory T cells in NZB/W mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S524 EP S525 PG 2 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877202400 ER PT J AU Shin, JJ Glickstein, LJ Steere, AC AF Shin, Junghee J. Glickstein, Lisa J. Steere, Allen C. TI Sustained, high levels of pro-inflammatory chemokines and cytokines in joint fluid and synovial tissue during the course of antibiotic-refractory lyme arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S94 EP S94 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877200157 ER PT J AU Panuzio, J O'Farrell, TJ Marshall, AD Murphy, CM Murphy, M Taft, CT AF Panuzio, Jillian O'Farrell, Timothy J. Marshall, Amy D. Murphy, Christopher M. Murphy, Marie Taft, Casey T. TI Intimate partner aggression reporting concordance and correlates of agreement among men with alcohol use disorders and their female partners SO ASSESSMENT LA English DT Article; Proceedings Paper CT SYMP IN HONOR OF MARCEL BESSIS CY FEB, 1986 CL LA JOLLA, CA DE physical aggression; psychological aggression; concordance; alcohol use disorders; relationship adjustment; antisocial personality disorder characteristics; psychopathic personality features ID BEHAVIORAL COUPLES THERAPY; MARITAL-STATUS INVENTORY; CONFLICT TACTICS SCALE; PHYSICAL AGGRESSION; GENDER DIFFERENCES; SOCIALIZATION SCALE; ANTISOCIAL-BEHAVIOR; DOMESTIC VIOLENCE; SUBSTANCE-ABUSERS; SPOUSAL VIOLENCE AB This study examined relationship aggression reporting concordance among 303 men with alcohol use disorders and their female partners enrolled in couples-based alcohol abuse treatment. Agreement for physical and psychological aggression was generally consistent with, or higher than, concordance rates reported among other populations. Men's antisocial personality disorder characteristics were the strongest predictor of higher concordance for male- and female-perpetrated aggression. Higher alcohol problem severity; poorer relationship adjustment, and higher psychopathic personality features were associated with better concordance in some analyses. Women reported experiencing more physical aggression than men reported perpetrating, and women reported perpetrating more psychological aggression than men reported experiencing. Findings highlight the importance of obtaining aggression reports from both partners and the need for research investigating methods for improving concordance. C1 VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM taft@bu.edu FU NIAAA NIH HHS [AA08637, AA10356, K02AA0234, R21AA12433] NR 95 TC 27 Z9 27 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD SEP PY 2006 VL 13 IS 3 BP 266 EP 279 DI 10.1177/1073191106287792 PG 14 WC Psychology, Clinical SC Psychology GA 076MN UT WOS:000239962500005 PM 16880279 ER PT J AU Koontz, AM Yang, YS Boninger, TDS Kanaly, J Cooper, RA Boninger, ML Dieruf, K Ewer, L AF Koontz, Alicia M. Yang, Yusheng Boninger, David S. Kanaly, John Cooper, Rory A. Boninger, Michael L. Dieruf, Kathy Ewer, Lynette TI Investigation of the performance of an ergonomic handrim as a pain-relieving intervention for manual wheelchair users SO ASSISTIVE TECHNOLOGY LA English DT Article DE ergonomic intervention; wheelchair handrims; carpal tunnel syndrome; propulsion biomechanics; manual wheelchair ID CARPAL-TUNNEL-SYNDROME; BEARING UPPER EXTREMITY; FORCE APPLICATION; PUSHRIM FORCES; PARAPLEGIC PATIENTS; TECHNICAL NOTE; 2 SPEEDS; PROPULSION; WEIGHT; BIOMECHANICS AB Manual wheelchair users commonly experience pain in their hands and wrists associated with the repetitive stress of propulsion. The objective of this research was to examine the effect of an ergonomic wheelchair handrim as an intervention designed to reduce pain in the hands and wrists and improve functional outcomes for manual wheelchair users. Three studies were conducted to achieve this objective. In the first study, 10 individuals with paraplegia underwent a biomechanical analysis before and after a 2-week practice period with a Natural-Fit (NF) prototype ergonomic handrim. The biomechanical results showed that grip moments were reduced with the NF handrim prototype as compared with the subjects' current handrim (p < .1). Other biomechanical findings were mixed. In the second study, 46 manual wheelchair users who replaced their standard handrim with the commercially available NF handrim completed a questionnaire of retrospective measures of symptom severity. Average duration of use of the NF was 6 months. When asked to compare propelling with the NF to propelling with their prior handrims, 85% of respondents reported less pain in their hands and 80% reported less pain in their wrists. The third study was a replication and extension of Study 2:82 manual wheelchair users who replaced their standard handrim with the NF completed retrospective symptom severity and functional status scales after using the NF for an average of 9 months. Results again confirmed that using the NF led to a reduction in the severity of symptoms and to improved functional outcomes. C1 VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Three Rivers Holdings LLC, Mesa, AZ USA. Univ Pittsburgh, Med Ctr Hlth Syst, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ New Mexico, Phys Therapy Program, Albuquerque, NM 87131 USA. RP Koontz, AM (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Yang, Yu-Sheng/0000-0002-2767-9354; Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [1R43-HD39962-01] NR 41 TC 9 Z9 9 U1 1 U2 4 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD FAL PY 2006 VL 18 IS 2 BP 123 EP 145 PG 23 WC Rehabilitation SC Rehabilitation GA 109CJ UT WOS:000242285200001 PM 17236472 ER PT J AU Ohnabe, H AF Ohnabe, Hisaichi TI Current trends in rehabilitation engineering in Japan SO ASSISTIVE TECHNOLOGY LA English DT Article; Proceedings Paper CT 28th International RESNA Conference CY JUN 23-27, 2005 CL Atlanta, GA DE rehabilitation engineering; assistive technology; elderly; disability; trend; Japan ID SYNCHRONIZATION AB In 2005, the elderly generation comprised 20% of the Japanese population. This percentage will grow to approximately 30% in 2030, meaning that nearly one in three people in Japan will be 65 years of age or older. Japan is the first nation in the world to face this situation. This article uses the context of Japanese society to give an overview of the elderly and people with disabilities; the International Classification of Functioning, Disability, and Health model; rehabilitation engineering-related policy; and education. In addition, we examine how governmental programs and Japanese law regarding technical aids may evolve by 2030. Partner robots, intelligent powered wheelchairs, nursing robots, and other technologies are introduced as examples of rehabilitation engineering and assistive technology. We also discuss the volunteer activities of the Rehabilitation Engineering Society of Japan (RESJA) in response to the Asian tsunami disaster and the achievements of a group of students from a Japanese senior high school of industry. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Sch Hlth & Rehabil Sci, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. RP Ohnabe, H (reprint author), Niigata Univ Hlth & Welf, Dept Prosthet & Orthot & Assist Technol, Sch Hlth Sci, 1398 Simami Cho, Niigata 9503198, Japan. NR 30 TC 5 Z9 5 U1 1 U2 2 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD FAL PY 2006 VL 18 IS 2 BP 220 EP 232 PG 13 WC Rehabilitation SC Rehabilitation GA 109CJ UT WOS:000242285200010 PM 17236481 ER PT J AU Cooper, RA AF Cooper, Rory A. TI Recent advances in structural joints and repairs for composite materials. SO ASSISTIVE TECHNOLOGY LA English DT Book Review C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Pittsburgh, PA USA. EM rcooper@pitt.edu NR 2 TC 0 Z9 0 U1 0 U2 2 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD FAL PY 2006 VL 18 IS 2 BP 233 EP 234 PG 2 WC Rehabilitation SC Rehabilitation GA 109CJ UT WOS:000242285200011 ER PT J AU Fu, YC Luo, LH Luo, NL Garvey, WT AF Fu, Yuchang Luo, Liehong Luo, Nanlan Garvey, W. Timothy TI Lipid metabolism mediated by adipocyte lipid binding protein (ALBP/aP2) gene expression in human THP-1 macrophages SO ATHEROSCLEROSIS LA English DT Article DE lipid binding protein; oxLDL; macrophage; foam cell; atherosclerosis ID FATTY-ACID-BINDING; LOW-DENSITY-LIPOPROTEIN; PPAR-GAMMA; OXIDIZED LDL; CHOLESTEROL EFFLUX; FOAM CELLS; ATHEROSCLEROSIS; RECEPTOR; OXIDATION; PATHWAY AB The critical initiating event in atherogenesis involves the invasion of monocytes through the endothelial wall of arteries, and their transformation from macrophages into foam cells. Human THP-1 monocytic cells can be induced to differentiate into macrophages by phorbol myristate acetate (PMA) treatment, and can then be converted into foam cells by exposure to oxidized low-density lipoprotein (oxLDL). We previously reported that adipocyte lipid binding protein (ALBP/aP2) is a gene that is highly up-regulated in foam cells in response to oxLDL. Here, we showed that overexpression of the ALBP gene using a lentiviral construct in macrophage foam cells enhanced the accumulations of cholesterol and triglyceride, probably due to an increased expression of the scavenger receptor type AI (SR-AI), which plays an important role in cell lipid metabolism. Moreover, we determined that the expression of acyl-coenzyme A: cholesterol-acyltransferase 1 (ACAT1) gene was up-regulated by the overexpression of ALBP gene, and on the other hand, the ATP-binding cassette A1 (ABCA1) gene and hormone sensitive lipase (HSL) gene, which mediate separately cholesterol efflux and cholesterol ester hydrolysis in the macrophage cells, were down-regulated by the overexpression of ALBP gene in these cells. Finally, our data indicated that oxLDL regulates expression of ALBP related to two peroxisome proliferator-responsive elements (PPREs) which are located in ALBP promoter region. These results have determined that ALBP gene expression accelerates cholesterol and triglyceride accumulation in macrophage foam cells and affects some key gene expression for lipid metabolism, suggesting some pivotal roles of ALBP in lipid metabolism for macrophage foam cell formation. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Fu, YC (reprint author), Univ Alabama, Dept Nutr Sci, 1676 Univ Blvd, Birmingham, AL 35294 USA. EM yfu@uab.edu FU NCRR NIH HHS [P20 RR16434]; NHLBI NIH HHS [P01-HL55782]; NIDDK NIH HHS [DK38764] NR 37 TC 33 Z9 44 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2006 VL 188 IS 1 BP 102 EP 111 DI 10.1016/j.atherosclerosis.2005.10.041 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 079LP UT WOS:000240178200013 PM 16313911 ER PT J AU Fried-Oken, M Fox, L Rau, MT Tullman, J Baker, G Hindal, M Wile, N Lou, JS AF Fried-Oken, Melanie Fox, Lynn Rau, Marie T. Tullman, Jill Baker, Glory Hindal, Mary Wile, Nancy Lou, Jau-Shin TI Purposes of AAC device use for persons with ALS as reported by caregivers SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE augmentative and alternative communication; amyotrophic lateral sclerosis; communication purposes; caregivers ID QUALITY-OF-LIFE AB Thirty-four informal caregivers who support 26 persons with ALS reported on AAC technology use. Each caregiver completed the Communication Device Use Checklist, a survey tool developed for this study based on Light's (1988) classification of the purposes of social interaction (Augmentative and Alternative Communication, 4, 66-82). The checklist includes 17 purposes of communication and asks participants to judge importance, mode, and frequency of use for each purpose. Results show that the three communication purposes used most frequently and valued as important by caregivers involve regulating the behavior of others for basic needs and wants ( getting needs met; giving instructions or directions to others; and clarifying needs). Consistent reports of use and frequency for the purposes of staying connected ( social closeness) and discussing important issues ( information transfer) indicate that AAC technology can assist the dyad in maintaining previous relationships. The face-to-face spontaneous conversation mode is used most frequently, despite the slow rate of production, the lack of permanence, and the demands on conversational partners during message generation. Clinical and research implications are discussed. C1 Oregon Hlth & Sci Univ, Oregon Inst Disabil & Dev, Portland, OR 97207 USA. Portland State Univ, Portland, OR 97207 USA. Portland VA Med Ctr, Portland, OR USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Fried-Oken, M (reprint author), Oregon Hlth & Sci Univ, Oregon Inst Disabil & Dev, POB 574, Portland, OR 97207 USA. EM friedm@ohsu.edu FU NICHD NIH HHS [R24HD39629] NR 23 TC 22 Z9 22 U1 1 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0743-4618 EI 1477-3848 J9 AUGMENT ALTERN COMM JI Augment. Altern. Commun. PD SEP PY 2006 VL 22 IS 3 BP 209 EP 221 DI 10.1080/07434610600650276 PG 13 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA 098AO UT WOS:000241492300005 PM 17114164 ER PT J AU Simon, NM Smoller, JW McNamara, KL Maser, RS Zalta, AK Pollack, MH Nierenberg, AA Fava, M Wong, KK AF Simon, Naomi M. Smoller, Jordan W. McNamara, Kate L. Maser, Richard S. Zalta, Alyson K. Pollack, Mark H. Nierenberg, Andrew A. Fava, Maurizio Wong, Kwok-Kin TI Telomere shortening and mood disorders: Preliminary support for a chronic stress model of accelerated aging SO BIOLOGICAL PSYCHIATRY LA English DT Article DE aging; bipolar; major depressive disorder; mood disorder; stress; telomere ID DEPRESSIVE SYMPTOMS; BIPOLAR DISORDER; MAJOR DEPRESSION; RISK; CANCER; LENGTH; HEALTH; CELLS; PATHOPHYSIOLOGY; MORTALITY AB Background: Little is known about the biological mechanisms underlying the excess medical morbidity and mortality associated with mood disorders. Substantial evidence supports abnormalities in stress-related biological systems in depression. Accelerated telomere shortening may reflect stress-related oxidative damage to cells and accelerated aging, and severe psychosocial stress has been linked to telomere shortening. We propose that chronic stress associated with mood disorders may contribute to excess vulnerability for diseases of aging such as cardiovascular disease and possibly some cancers through accelerated organismal aging. Methods. Telomere length was measured by Southern Analysis in 44 individuals with chronic mood disorders and 44 nonpsychiatrically ill age-matched control subjects. Results. Telomere length was significantly shorter in those with mood disorders, representing as much as 10 years of accelerated aging. Conclusions: These results provide preliminary evidence that mood disorders are associated with accelerated aging and may suggest a novel mechanism for mood disorder-associated morbidity and mortality. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM NSIMON@Partners.org RI Maser, Richard/B-2970-2012; OI Zalta, Alyson/0000-0002-5159-8431; wong, kwok kin/0000-0001-6323-235X FU NIA NIH HHS [K08AG2400401]; NIMH NIH HHS [K08-MH01770, MH01831-01] NR 27 TC 237 Z9 244 U1 5 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2006 VL 60 IS 5 BP 432 EP 435 DI 10.1016/j.biopsych.2006.02.004 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 084BH UT WOS:000240506000002 PM 16581033 ER PT J AU Parkman, R Cohen, G Carter, SL Weinberg, KI Masinsin, B Guinan, E Kurtzberg, J Wagner, JE Kernan, NA AF Parkman, Robertson Cohen, Geoff Carter, Shelly L. Weinberg, Kenneth I. Masinsin, Bernadette Guinan, Eva Kurtzberg, Joanne Wagner, John E. Kernan, Nancy A. TI Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE immune reconstitution; tumor immunity ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; IMMUNODEFICIENCY-VIRUS TYPE-1; HOST-DISEASE; THYMIC FUNCTION; T-CELLS; ADULT PATIENTS AB Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival. 2006 American Society for Blood and Marrow Transplantation. C1 Childrens Hosp Los Angeles, Saban Res Inst, Div Res Immunol Bone Marrow Transplantat, Los Angeles, CA 90027 USA. EMMES Corp, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Minnesota, Minneapolis, MN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Parkman, R (reprint author), Childrens Hosp Los Angeles, Saban Res Inst, Div Res Immunol Bone Marrow Transplantat, 4650 Sunset Blvd,Mail Stop 62, Los Angeles, CA 90027 USA. EM rparkman@chla.usc.edu OI Kernan, Nancy/0000-0003-1417-1823 FU NCI NIH HHS [P01-CA100265]; NHLBI NIH HHS [N01-HB-67113, N01-HB-67132, N01-HB-67135, N01-HB-67138, N01-HB-67139] NR 36 TC 82 Z9 87 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2006 VL 12 IS 9 BP 919 EP 927 DI 10.1016/j.bbmt.2006.05.008 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 082AK UT WOS:000240358500004 PM 16920557 ER PT J AU Yeo, Y Highley, CB Bellas, E Ito, T Marini, R Langer, R Kohane, DS AF Yeo, Yoon Highley, Christopher B. Bellas, Evangelia Ito, Taichi Marini, Robert Langer, Robert Kohane, Daniel S. TI In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model SO BIOMATERIALS LA English DT Article DE post-operative adhesion; in situ cross-linkable hydrogel; hyaluronic acid; barrier; rabbit sidewall defect-cecum abrasion model ID POSTSURGICAL ADHESIONS; PLASMINOGEN-ACTIVATOR; REDUCTION; INHIBITION; BARRIERS; OXYGEN; GEL AB We studied the efficacy of an in situ cross-linked hyaluronic acid hydrogel (HAX) in preventing post-surgical peritoneal adhesions, using a rabbit sidewall defect-cecum abrasion model. Two cross-linkable precursors were prepared by modifying hyaluronic acid with adipic dihydrazide and aldehyde, respectively. The hydrogel precursors cross-linked to form a flexible hydrogel upon mixing. The hydrogel was biodegradable and provided a durable physical barrier, which was highly effective in reducing the formation of postoperative adhesions. Ten out of 12 animals in the untreated control group developed fibrous adhesions requiring sharp dissection, while only 2 out of 8 animals treated with HAX gels showed such adhesions, and those occurred in locations that were not covered by the hydrogel. We also studied means by which gel degradation time can be modulated by varying the precursor concentration and molecular weight. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, Pediat Intens Care Unit, Ellison 317,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM073626] NR 32 TC 103 Z9 107 U1 3 U2 46 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2006 VL 27 IS 27 BP 4698 EP 4705 DI 10.1016/j.biomaterials.2006.04.043 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 067HA UT WOS:000239291300004 PM 16750564 ER PT J AU Karp, JM Yeo, Y Geng, WL Cannizarro, C Yan, K Kohane, DS Vunjak-Novakovic, G Langer, RS Radisic, M AF Karp, Jeffrey M. Yeo, Yoon Geng, Wenlinag Cannizarro, Christopher Yan, Kenny Kohane, Daniel S. Vunjak-Novakovic, Gordana Langer, Robert S. Radisic, Milica TI A photolithographic method to create cellular micropatterns SO BIOMATERIALS LA English DT Article DE photolithography; chitin/chitosan; micropatterning; osteoblast; cardiomyocyte; fibroblast ID CARDIAC TISSUE; IN-VITRO; LIVING CELLS; MICROSTRUCTURES; CHITOSAN; COCULTURES; HYDROGELS; MYOCYTES; GROWTH; FABRICATION AB Here we describe a simple and rapid system for creation of patterned cell culture substrates. This technique is based on (1) printing a mask on a standard overhead transparency, (2) coating a thin layer of a photocrosslinkable chitosan on a slide, (3) exposing the slide and mask to ultraviolet (UV) light, and (4) rinsing the uncrosslinked polymer to expose the underlying cell-repellent patterns. Photocross-linkable chitosan does not require photoinitiators, it is non-toxic and forms flexible, biocompatible hydrogel upon short (similar to min) UV exposure. Patterns of various shapes (lanes, squares, triangles, circles) were created on two surfaces commonly used for cell culture: glass and tissue culture polystyrene. The pattern size could be varied with a pm resolution using a single mask and varying UV exposure time. Cardiac fibroblasts formed stable patterns for up to 18 days in culture. Cardiomyocytes, patterned in lanes 68-99 mu m wide, exhibited expression of cardiac Troponin I, well developed contractile apparatus and they contracted synchronously in response to electrical field stimulation. Osteoblasts (SAOS-2) localized in the exposed glass regions (squares, triangles, or circles; 0.063-0.5 mm(2)). They proliferated to confluence in 5 days, expressed alkaline phosphatase and produced a mineralized matrix. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Toronto, Inst Biomat & Biomat Engn, Toronto, ON M5S 3G9, Canada. Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3E5, Canada. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Radisic, M (reprint author), Univ Toronto, Inst Biomat & Biomat Engn, 164 Coll St,Rm 407, Toronto, ON M5S 3G9, Canada. EM milica@chem-eng.utoronto.ca OI Vunjak-Novakovic, Gordana/0000-0002-9382-1574 NR 30 TC 65 Z9 67 U1 3 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2006 VL 27 IS 27 BP 4755 EP 4764 DI 10.1016/j.biomaterials.2006.04.028 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 067HA UT WOS:000239291300010 PM 16730059 ER PT J AU Murthy, SK Sethu, P Vunjak-Novakovic, G Toner, M Radisic, M AF Murthy, Shashi K. Sethu, Palaniappan Vunjak-Novakovic, Gordana Toner, Mehmet Radisic, Milica TI Size-based microfluidic enrichment of neonatal rat cardiac cell populations SO BIOMEDICAL MICRODEVICES LA English DT Article ID SHEAR-STRESS; MUSCLE; TISSUE; SEPARATION; OXYGEN AB Native heart consists of myocytes and non-myocytes. We demonstrate here the feasibility of a size-based microfluidic separation of myocytes and non-myocytes from the neonatal rat myocardium. The device consists of a middle channel (50 mu m wide, 200 mu m tall, and 4 cm long) connected to adjacent side channels by microsieves (80 mu m wide, 5 mu m tall and 40 mu m in length). The side channels increase in width in a flared shape along the length of the device to ensure constant pressure gradient across all sieves. In the first step, non-myoctes were removed from the myocytes by a conventional pre-plating method for 75 min. Subsequently, the non-myocytes were further enriched in a microfludic device at 20 mu l/min. We demonstrated that the cells in the middle and side channels maintained viability during sorting and the ability to attach and grow in culture. Upon culture for 48 h cardiomyocytes from the reservoir (control) and middle channel stained positive for cardiac Troponin I, exhibited a well developed contractile apparatus and contracted spontaneously and in response to electrical field stimulation. Most of the cells in the side channel expressed a non-myocyte marker vimetin. Fluorescent activated cell sorting indicated significant enrichment in the side channel (p < 0.001) for non-myocytes. Original cell suspension had a bimodal cell size distribution with the peaks in the range from 7-9 mu m and 15-17 mu m. Upon cell sorting the distribution was Gaussian in both side channel and middle channel with the peaks in the range 7-9 mu m and 9-11 mu m respectively, indicating that the separation by size occurred. C1 Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3G9, Canada. RP Radisic, M (reprint author), Univ Toronto, Inst Biomat & Biomed Engn, 164 Coll St RS 407, Toronto, ON M5S 3G9, Canada. EM milica@chem-eng.utoronto.ca OI Vunjak-Novakovic, Gordana/0000-0002-9382-1574 FU NHLBI NIH HHS [R01 HL 076485]; NIBIB NIH HHS [P41 EB 02503, P41 EB 002520-01A1, P41 EB002503, P41 EB002520] NR 22 TC 45 Z9 46 U1 0 U2 18 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD SEP PY 2006 VL 8 IS 3 BP 231 EP 237 DI 10.1007/s10544-006-8169-5 PG 7 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 072HN UT WOS:000239664600006 PM 16732418 ER PT J AU Shin, M King, K Matsuda, K Ishii, O Terai, H Weinberg, E Kaazempur-Mofrad, M Borenstein, J Detmar, M Vacanti, J AF Shin, Michael King, Kevin Matsuda, Kant Ishii, Osamu Terai, Hidetomi Weinberg, Eli Kaazempur-Mofrad, Mohammed Borenstein, Jeffrey Detmar, Michael Vacanti, Joseph TI Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane) (vol 6, pg 269, 2004) SO BIOMEDICAL MICRODEVICES LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Charles Stark Draper Lab Inc, MEMS Technol Grp, Cambridge, MA 02139 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Ctr Integrat Med & Innovat Technol, Cambridge, MA 02139 USA. RP Shin, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 1 TC 3 Z9 3 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD SEP PY 2006 VL 8 IS 3 BP 271 EP 271 DI 10.1007/s10544-006-9598-x PG 1 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 072HN UT WOS:000239664600011 ER PT J AU Masaki, K Weiss, TF Freeman, DM AF Masaki, Kinuko Weiss, Thomas F. Freeman, Dennis M. TI Poroelastic bulk properties of the tectorial membrane measured with osmotic stress SO BIOPHYSICAL JOURNAL LA English DT Article ID POLYELECTROLYTE GEL MODEL; CONNECTIVE-TISSUE; EQUILIBRIUM BEHAVIOR; ISOSMOTIC SOLUTIONS; COCHLEAR ENDOLYMPH; CA2+ CONCENTRATION; INNER-EAR; BODY WALL; CARTILAGE; MORPHOLOGY AB The equilibrium stress-strain relation and the pore radius of the isolated tectorial membrane (TM) of the mouse were determined. Polyethylene glycol (PEG), with molecular mass (MM) in the range 20-511 kDa, added to the TM bathing solution was used to exert an osmotic pressure. Strain on the TM induced by isosmotic PEG solutions of different molecular masses was approximately the same for MM >= 200 kDa. However, for MM <= 100 kDa, the TM strain was appreciably smaller. We infer that for the smaller molecular mass, PEG entered the TM and exerted a smaller effective osmotic pressure. The pore radius of the TM was estimated as 22 nm. The equilibrium stress-strain relation of the TM was measured using PEG with a molecular mass of 511 kDa. This relation was nonlinear and was fit with a power function. In the radial cochlear direction, the transverse stiffness of the TM was 20% stiffer in the inner than in the outer region. TM segments from the basal region had a larger transverse stiffness on average compared to sections from the apical-middle region. These measurements provide a quantitative basis for a poroelastic model of the TM. C1 MIT, Harvard MIT Speech & Hearing Sci Program, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Freeman, DM (reprint author), MIT, Harvard MIT Speech & Hearing Sci Program, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM freeman@mit.edu FU NIDCD NIH HHS [R01 DC000238, R01 DC 00238] NR 64 TC 15 Z9 15 U1 3 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2006 VL 91 IS 6 BP 2356 EP 2370 DI 10.1529/biophysj.105.078121 PG 15 WC Biophysics SC Biophysics GA 078US UT WOS:000240130500041 PM 16815909 ER PT J AU Tefferi, A Barosi, G Mesa, RA Cervantes, F Deeg, HJ Reilly, JT Verstovsek, S Dupriez, B Silver, RT Odenike, O Cortes, J Wadleigh, M Solberg, LA Camoriano, JK Gisslinger, H Noel, P Thiele, J Vardiman, JW Hoffman, R Cross, NCP Gilliland, DG Kantarjian, H AF Tefferi, Ayalew Barosi, Giovanni Mesa, Ruben A. Cervantes, Francisco Deeg, H. Joachim Reilly, John T. Verstovsek, Srdan Dupriez, Brigitte Silver, Richard T. Odenike, Olatoyosi Cortes, Jorge Wadleigh, Martha Solberg, Lawrence A., Jr. Camoriano, John K. Gisslinger, Heinz Noel, Pierre Thiele, Juergen Vardiman, James W. Hoffman, Ronald Cross, Nicholas C. P. Gilliland, D. Gary Kantarjian, Hagop TI International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT) SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; LOW-DOSE THALIDOMIDE; LEUKEMIA GROUP-B; MYELODYSPLASTIC SYNDROMES; IDIOPATHIC MYELOFIBROSIS; INTERFERON-ALPHA; CYTOGENETIC ABNORMALITIES; MARROW-TRANSPLANTATION; LENALIDOMIDE CC-5013; CIRCULATING CD34(+) AB Myelofibrosis with myeloid metaplasia (MMM) is a clinicopathologic entity characterized by stem cell-derived clonal myeloproliferation, ineffective erythropoiesis, extramedullary hematopoiesis, and bone marrow fibrosis and osteosclerosis. Patients with MMM have shortened survival and their quality of life is compromised by progressive anemia, marked hepatosplenomegaly, and severe constitutional symptoms including cachexia. After decades of frustration with ineffective therapy, patients are now being served by promising treatment approaches that include allogeneic hematopoietic stem cell transplantation and immunomodulatory drugs. Recent information regarding disease pathogenesis, including a contribution to the myeloproliferative disorder phenotype by a gain-of-function JAK2 mutation (JAK2(V617F)), has revived the prospect of targeted therapeutics as well as molecular monitoring of treatment response. Such progress calls for standardization of response criteria to accurately assess the value of new treatment modalities, to allow accurate comparison between studies, and to ensure that the definition of response reflects meaningful health outcome. Accordingly, an international panel of experts recently convened and delineated 3 response categories: complete remission (CR), partial remission (PR), and clinical improvement (CI). Bone marrow histologic and hematologic remissions characterize CR and CR/PR, respectively. The panel agreed that the CI response category is applicable only to patients with moderate to severe cytopenia or splenomegaly. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Policlin San Matteo, Ist Ric & Curo Carattere Sci, I-27100 Pavia, Italy. Hosp Clin Barcelona, Inst Invest Biomed August Pi I Sunyer, E-08036 Barcelona, Spain. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cornell Univ, Med Ctr, New York, NY 10021 USA. Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. Univ Vienna, Dept Hematol & Blood Coagulat, Vienna, Austria. NIH, Bethesda, MD 20892 USA. Univ Cologne, Inst Pathol, D-5000 Cologne, Germany. Univ Illinois, Chicago, IL USA. Wessex Reg Genet Lab, Salisbury, Wilts, England. RP Tefferi, A (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu RI Cross, Nicholas/B-4817-2009; Solberg, Lawrence/A-3824-2014 OI Cross, Nicholas/0000-0001-5481-2555; Solberg, Lawrence/0000-0001-9550-5180 NR 53 TC 196 Z9 210 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2006 VL 108 IS 5 BP 1497 EP 1503 DI 10.1182/blood-2006-03-009746 PG 7 WC Hematology SC Hematology GA 080TO UT WOS:000240271500018 PM 16675707 ER PT J AU Zorn, E Nelson, EA Mohseni, M Porcheray, F Kim, H Litsa, D Bellucci, R Raderschall, E Canning, C Soiffer, RJ Frank, DA Ritz, J AF Zorn, Emmanuel Nelson, Erik A. Mohseni, Mehrdad Porcheray, Fabrice Kim, Haesook Litsa, Despina Bellucci, Roberto Raderschall, Elke Canning, Christine Soiffer, Robert J. Frank, David A. Ritz, Jerome TI IL-2 regulates FOXP3 expression in human CD4(+)CD25(+) regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; DOSE RECOMBINANT INTERLEUKIN-2; NATURAL-KILLER-CELLS; TRANSCRIPTION FACTOR FOXP3; CONTINUOUS-INFUSION; PROLONGED INFUSION; TOLERANCE; MELANOMA; RECEPTOR AB IL-2 plays a critical role in the maintenance of CD4(+)CD25(+) FOXP3(+) regulatory T cells (Tregs) in vivo. We examined the effects of IL-2 signaling in human Tregs. In vitro, IL-2 selectively up-regulated the expression of FOXP3 in purified CD4(+)CD25(+) T cells but not in CD4(+)CD25(-) cells. This regulation involved the binding of STAT3 and STAT5 proteins to a highly conserved STAT-binding site located in the first intron of the FOXP3 gene. We also examined the effects of low-dose IL-2 treatment in 12 patients with metastatic cancer and 9 patients with chronic myelogenous leukemia after allogeneic hematopoietic stem cell transplantation. Overall, IL-2 treatment resulted in a 1.9 median fold increase in the frequency of CD4(+)CD25(+) cells in peripheral blood as well as a 9.7 median fold increase in FOXP3 expression in CD3(+) T cells. CD56(+)CD3(-) natural killer (NK) cells also expanded during IL-2 therapy but did not express FOXP3. In vitro treatment of NK cells with 5-aza-2'-deoxycytidine restored the IL-2 signaling pathway leading to FOXP3expression, suggesting that this gene was constitutively repressed by DNA methylation in these cells. Our findings support the clinical evaluation of low-dose IL-2 to selectively modulate CD4(+)CD25+ Tregs and increase expression of FOXP3in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Maligancies, Boston, MA 02115 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Maligancies, 44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu FU NHLBI NIH HHS [HL70149]; NIAID NIH HHS [AI29530] NR 52 TC 341 Z9 372 U1 1 U2 13 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2006 VL 108 IS 5 BP 1571 EP 1579 DI 10.1182/blood-2006-02-004747 PG 9 WC Hematology SC Hematology GA 080TO UT WOS:000240271500029 PM 16645171 ER PT J AU Chan, IT Kutok, JL Williams, IR Cohen, S Moore, S Shigematsu, H Ley, TJ Akashi, K Le Beau, MM Gilliland, DG AF Chan, Iris T. Kutok, Jeffery L. Williams, Ifor R. Cohen, Sarah Moore, Sandra Shigematsu, Hirokazu Ley, Timothy J. Akashi, Koichi Le Beau, Michelle M. Gilliland, D. Gary TI Oncogenic K-ras cooperates with PML-RAR alpha to induce an acute promyelocytic leukemia-like disease SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; RECURRING CHROMOSOMAL-ABNORMALITIES; TRANSGENIC MICE; RETINOIC ACID; MOUSE MODEL; CONDITIONAL EXPRESSION; SOMATIC ACTIVATION; ARSENIC TRIOXIDE; PML/RAR-ALPHA; N-RAS AB Most patients with acute promyelocytic leukemia (APL) express PML-RAR alpha, the fusion product of t(15;17)(q22;q11.2). Transgenic mice expressing PML-RAR alpha develop APL with long latency, low penetrance, and acquired cytogenetic abnormalities. Based on observations that 4% to 10% of APL patients harbor oncogenic ras mutations, we coexpressed oncogenic K-ras from its endogenous promoter with PML-RARa to generate a short-latency, highly penetrant mouse model of APL. The APL disease was characterized by splenomegaly, leukocytosis, extramedullary hematopoiesis (EMH) in spleen and liver with an increased proportion of immature myeloperoxidase-expressing myeloid forms; transplantability to secondary recipients; and lack of cytogenetic abnormalities. Bone marrow cells showed enhanced self-renewal in vitro. This model establishes a role for oncogenic ras in leukemia pathogenesis and thus validates the oncogenic RAS signaling pathway as a potential target for therapeutic inhibition in leukemia patients. This mouse model should be useful for investigating signaling pathways that promote self-renewal in APL and for testing the in vivo efficacy of RAS signaling pathway inhibitors in conjunction with other targeted therapies such as ATRA (all trans retinoic acid) and arsenic trioxide. C1 Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Emory Univ, Dept Pathol, Sch Med, Atlanta, GA 30322 USA. Washington Univ, Sch Med, Div Oncol, Dept Med,Siteman Canc Ctr, St Louis, MO USA. Washington Univ, Sch Med, Div Oncol, Dept Genet,Siteman Canc Ctr, St Louis, MO USA. Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. RP Chan, IT (reprint author), Karp Family Res Bldg,1 Blackfan Circle,5th Floor, Boston, MA 02115 USA. EM iris_chan@dfci.harvard.edu; ggilliland@rics.bwh.harvard.edu RI Williams, Ifor/D-3648-2011 OI Williams, Ifor/0000-0002-8810-2911 FU NCI NIH HHS [CA66996, K08 CA109117, U01 CA84221]; NIDDK NIH HHS [DK51564] NR 44 TC 34 Z9 38 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 SEP 1 PY 2006 VL 108 IS 5 BP 1708 EP 1715 DI 10.1182/blood-2006-04-015040 PG 8 WC Hematology SC Hematology GA 080TO UT WOS:000240271500046 PM 16675706 ER PT J AU Viswanathan, A Guichard, JP Gschwendtner, A Buffon, F Cumurcuic, R Boutron, C Vicaut, E Holtmannspotter, M Pachai, C Bousser, MG Dichgans, M Chabriat, H AF Viswanathan, Anand Guichard, Jean-Pierre Gschwendtner, Andreas Buffon, Frederique Cumurcuic, Rodica Boutron, Carole Vicaut, Eric Holtmannspoetter, Markus Pachai, Chahin Bousser, Marie-Germaine Dichgans, Martin Chabriat, Hugues TI Blood pressure and haemoglobin AIc are associated with microhaemorrhage in CADASIL: a two-centre cohort study SO BRAIN LA English DT Article DE CADASIL; cerebral microhaemorrhage; lacunes; white matter damage; haemogloblin A I c ID AUTOSOMAL-DOMINANT ARTERIOPATHY; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; CEREBRAL AMYLOID ANGIOPATHY; CARDIOVASCULAR RISK-FACTORS; STATE-EXAMINATION MMSE; ACUTE ISCHEMIC-STROKE; SUBCORTICAL INFARCTS; DISEASE PROGRESSION; NOTCH3 MUTATIONS; GLUCOSE LEVEL AB Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The risk factors for cerebral microhaemorrhages (CM), their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined. Our purpose was to examine the frequency, number and location of microhaemorrhages in a multicentre cohort study, defining predisposing factors and associated radiographic markers in CADASIL patients. We collected clinical data from 147 consecutive patients enrolled in an ongoing prospective cohort study. Degree of neurological disability and cognitive impairment were assessed by standardized scales. T-1-weighted, FLAIR and T-2*-weighted gradient-echo (GE) MRI sequences were performed. Volume and location of lacunar infarcts and white matter hyperintensity (WMH) were assessed. Number and location of CM were recorded. CM were present in 35% patients, most commonly occurring in the thalamus, brainstem and basal ganglia. The location of CM qualitatively differed from areas of lacunar infarction and WMH. There was a significant association between the presence of CM and a history of hypertension (P = 0.005), systolic blood pressure (SBP) (P = 0.014), haemoglobin Alc (HbAlc) (P = 0.004) and the volume of lacunar infarcts (P = 0.010) and WMHs (P = 0.046). The number of CM was independently associated with SBP (P = 0.005), the diagnosis of hypertension (P = 0.0004), volume of WMH (P = 0.0005) and lacunar infarcts (P = 0.004). In contrast, no association was found between blood pressure or HbA1c and the load of WMH or lacunar infarcts. The presence of CM was independently associated with increased modified Rankin scores. CM are independently associated with blood pressure and HbA1c as well as with lacunar infarct and WMH volume in CADASIL. Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers, suggesting a distinct pathological process. These lesions have a potential clinical impact in CADASIL. These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease. C1 CHU Lariboisiere, Assistance Publ Hop Paris, Dept Neurol, Paris, France. CHU Lariboisiere, Assistance Publ Hop Paris, Dept Neuroradiol, Paris, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Munich, Klinikum Grosshadern, Dept Neurol, D-8000 Munich, Germany. Univ Munich, Klinikum Grosshadern, Dept Neuroradiol, D-8000 Munich, Germany. THERALYS, Lyon, France. RP Chabriat, H (reprint author), Hop Lariboisiere, Neurol Serv, 2 Rue Ambroise Pare, F-75010 Paris, France. EM hugues.chabriat@lrb.ap-hop-paris.fr RI Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 57 TC 82 Z9 84 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2006 VL 129 BP 2375 EP 2383 DI 10.1093/brain/awl177 PN 9 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 086NG UT WOS:000240679700013 PM 16844717 ER PT J AU Aldape, K Phillips, H Zhang, L Nutt, C Louis, D Jenkins, R Feuerstein, B Colman, H AF Aldape, Ken Phillips, Heidi Zhang, Li Nutt, Catherine Louis, David Jenkins, Robert Feuerstein, Burt Colman, Howard TI Meta-analysis of microarray data from glioblastoma samples identifies a robust multigene predictor of outcome SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 004 BP S2 EP S2 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600005 ER PT J AU Billiards, SS Folkerth, RD Haynes, RL Borenstein, NS Trachtenberg, FL Rowitch, DH Ligon, KL Volpe, JJ Kinney, HC AF Billiards, Saraid S. Folkerth, Rebecca D. Haynes, Robin L. Borenstein, Natalia S. Trachtenberg, Felicia L. Rowitch, David H. Ligon, Keith L. Volpe, Joseph J. Kinney, Hannah C. TI Oligodendrocyte analysis in periventricular leukomalacia in the human brain SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 190 BP S87 EP S87 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600191 ER PT J AU Chan, JA Nazemi, KJ Choi, Y Segal, RA AF Chan, Jennifer A. Nazemi, Kellie J. Choi, Yoojin Segal, Rosalind A. TI Heparan sulfate proteoglycans spatially restrict the sonic hedgehog mitogen response SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurobiol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 357 BP S160 EP S160 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600358 ER PT J AU Freeman, SH Raju, S Hyman, BT Frosch, MP Irizarry, MC AF Freeman, Stefanie H. Raju, Susan Hyman, Bradley T. Frosch, Matthew P. Irizarry, Michael C. TI Plasma AB levels do not reflect brain AB levels SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 276 BP S124 EP S124 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600277 ER PT J AU Gejman, R Swearingen, B Hedley-Whyte, ET AF Gejman, Roger Swearingen, Brooke Hedley-Whyte, E. Tessa TI Role of Ki67 proliferation index and p53 expression in predicting progression of pituitary adenomas SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 242 BP S110 EP S110 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600243 ER PT J AU Gray, F Baudrimont, M Viswanathan, A Chabriat, H Mikol, J AF Gray, Francoise Baudrimont, Marie Viswanathan, Anand Chabriat, Hughes Mikol, Jacqueline TI Neuronal apoptosis in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Univ Paris 07, APHP, Hop Lariboisiere, F-75221 Paris 05, France. CHU Brest, F-29285 Brest, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 197 BP S90 EP S90 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600198 ER PT J AU Kulich, SM Horbinski, C Chu, CT AF Kulich, Scott M. Horbinski, Craig Chu, Charleen T. TI Characterization of 6-OHDA-elicited superoxide in cytotoxicity SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 140 BP S64 EP S64 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600141 ER PT J AU Louis, DN Cahill, D Futreal, A Stratton, M AF Louis, David N. Cahill, Daniel Futreal, Andy Stratton, Mike TI Somatic mutations of the mismatch repair gene MSH6 in human glioblastomas recurrent after temozolomide chemotherapy SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 001 BP S1 EP S1 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600001 ER PT J AU Rousseau, A Nutt, CL Betensky, RA Iafrate, AJ Ligon, KL Rowitch, DH Louis, DN AF Rousseau, Audrey Nutt, Catherine L. Betensky, Rebecca A. Iafrate, A. J. Ligon, Keith L. Rowitch, David H. Louis, David N. TI Expression of oligodendroglial and astrocytic lineage markers in diffuse gliomas SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Harvard Univ, Sch Med, Mol Pathol Unit, MGH,INSERM,U495, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Mol Pathol Unit, MGH, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RI Nutt, Catherine/K-8794-2012; Rousseau, Audrey/L-3193-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 080 BP S37 EP S37 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600081 ER PT J AU Saad, AG Chi, S Kieran, M DeGirolami, U AF Saad, Ali G. Chi, Susan Kieran, Mark DeGirolami, Umberto TI The role of hypercellular nodules and MIB-1 labeling index in pediatric who grade II ependymomas SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 053 BP S25 EP S25 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600054 ER PT J AU William, CM Louis, DN Nutt, C AF William, Christopher M. Louis, David N. Nutt, Catherine TI Molecular characterization of common genetically defined subtypes of glioblastoma SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 060 BP S28 EP S28 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600061 ER PT J AU Xun, Z Gejman, R Ansell, P Batista, D Zhou, YL Louis, DN Klibanski, A AF Xun, Zhang Gejman, Roger Ansell, Peter Batista, Dalia Zhou, Yunli Louis, David N. Klibanski, Anne TI Loss of MEG3 expression in human meningiomas: Potential association with tumor progression SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 16th International Congress of Neuropathology CY SEP 10-15, 2006 CL San Francisco, CA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2006 VL 16 SU 1 MA 220 BP S100 EP S100 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 076EA UT WOS:000239938600221 ER PT J AU Kuchenbauer, F Schnittger, S Look, T Gilliland, G Tenen, D Haferlach, T Hiddemann, W Buske, C Schoch, C AF Kuchenbauer, F. Schnittger, S. Look, T. Gilliland, G. Tenen, D. Haferlach, T. Hiddemann, W. Buske, C. Schoch, C. TI Identification of additional cytogenetic and molecular genetic abnormalities in acute myeloid leukaemia with t(8;21)/AML1-ETO SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute myeloid leukaemia; AML1-ETO; receptor tyrosine kinases; leukaemogenesis; multistep model ID MUTATIONS AB AML1-ETO collaborates with further genetic abnormalities to induce acute myeloid leukaemia (AML). We analysed 99 patients with an AML1-ETO rearrangement for additional aberrations. Frequent genetic abnormalities were, loss of a sex chromosome (56/99, 56.5%) and del(9)(q22) (24/99, 24.2%). The most frequent molecular aberrations were mutations of KITD816 (3/23, 13%) and NRAS (8/89, 8.9%). Further molecular abnormalities were FLT3 mutations (3/87, 3.4%), AML1 (1/26, 3.8%) and PU1 (1/14, 7.1%). MLL-PTD, KRAS and CEBPA mutations were not found. These clinical findings support the model that AML1-ETO collaborates with other genetic alterations, such as mutations of receptor tyrosine kinases, to induce AML. C1 GSF, Clin Cooperat Grp Leukemia, Munich, Germany. Univ Munich, Dept Med 3, Munich, Germany. MLL, Munich Leukemia Lab, Munich, Germany. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. RP Kuchenbauer, F (reprint author), Terry Fox Lab, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM fkuchenbauer@web.de OI Tenen, Daniel/0000-0002-6423-3888 NR 12 TC 34 Z9 37 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2006 VL 134 IS 6 BP 616 EP 619 DI 10.1111/j.1365-2141.2006.06229.x PG 4 WC Hematology SC Hematology GA 075BQ UT WOS:000239857600007 PM 16938118 ER PT J AU Stewart, AJ Viswanathan, AN AF Stewart, Alexandra J. Viswanathan, Akila N. TI Current controversies in high-dose-rate versus low-dose-rate brachytherapy for cervical cancer SO CANCER LA English DT Review DE stage III cervical cancer; high-dose-rate (HDR) brachytherapy; low-dose-rate (LDR) brachytherapy; concomitant chemotherapy ID RATE INTRACAVITARY BRACHYTHERAPY; EXTERNAL-BEAM RADIOTHERAPY; LOCALLY ADVANCED-CARCINOMA; UTERINE CERVIX; RADIATION-THERAPY; INTERSTITIAL BRACHYTHERAPY; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; AFTERLOADING BRACHYTHERAPY; TREATMENT PROLONGATION AB The use of brachytherapy in the treatment of cervical cancer has increased worldwide since its initial introduction over 100 years ago. However, certain aspects of the use of high-dose-rate (HDR) versus low-dose-rate (LDR) brachytherapy continue to be controversial, particularly the role of HDR in FIGO Stage III cervical cancer and the use of HDR with concurrent chemotherapy. This study represents a systematic literature review of prospective and retrospective series of patients with cervical carcinoma treated with external-beam radiation (EBRT) followed by either HDR or LDR radiation. The local control rates, survival rates, and treatment-related complications in patients with Stage III cervical cancer treated with HDR or LDR and those treated with concomitant chemotherapy are examined. Patients with Stage III cervical cancer treated with EBRT and brachytherapy have a local control rate of > 50% in most series. Randomized prospective and retrospective studies show overall statistically equivalent local control, overall survival, and complication rates between HDR and LDR. However, LDR may be preferable for large, bulky tumors at the time of brachytherapy. Retrospective studies of HDR and concurrent chemotherapy are limited but have demonstrated toxicity rates similar to those with LDR. Selected patients with Stage III cervical carcinoma who have an adequate response to EBRT and concomitant chemotherapy may be treated with HDR brachytherapy. The existing literature shows no significant increase in complications in patients treated with HDR and concurrent chemotherapy; however, sufficient tumor shrinkage prior to HDR and careful monitoring of the dose to the normal tissues are imperative. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@partners.org FU NCI NIH HHS [R25 CA089017] NR 60 TC 38 Z9 42 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2006 VL 107 IS 5 BP 908 EP 915 DI 10.1002/cncr.22054 PG 8 WC Oncology SC Oncology GA 077TV UT WOS:000240054200003 PM 16874815 ER PT J AU Nakabayashi, M Xie, WL Regan, MM Jackman, DM Kantoff, PW Oh, WK AF Nakabayashi, Mari Xie, Wanling Regan, Meredith M. Jackman, David M. Kantoff, Philip W. Oh, William K. TI Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer SO CANCER LA English DT Article DE ketoconazole; low dose; dose escalation; androgen-independent prostate cancer; secondary hormonal therapy; prostate-specific antigen response ID DRUG-METABOLISM; MEN; HYDROCORTISONE; MITOXANTRONE; THERAPY; BIOSYNTHESIS; INHIBITION; PREDNISONE; WITHDRAWAL; DOCETAXEL AB BACKGROUND. High-dose ketoconazole (HDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen-independent prostate cancer (AlPC). However, HDK causes more severe adverse events than low-dose ketoconazole (LDK). To the authors' knowledge, relatively little is known regarding the efficacy of LDK in AIPC. The efficacy of LDK and of subsequent dose escalation from LDK to HDK was evaluated as secondary hormonal therapy in patients with AIPC. METHODS. in a single institution, patients with AIPC treated with LDK (at a dose of 200 mg orally 3 times daily) as secondary hormonal therapy with or without concomitant steroids were retrospectively identified. In addition, patients were identified who received dose escalation to HDK (400 mg orally 3 times daily) after experiencing a rising prostate-specific antigen (PSA) level. RESULTS. Thirty-nine of 138 eligible patients (28.3%, 95% confidence interval [95% CI], 20.9-36.6%) treated with LDK experienced PSA declines >= 50%. The median time to disease progression or dose escalation on LDK was 3.2 months (range, 0.1(+)-61 months). Dose escalation to HDK was subsequently performed in 55 patients (39.9%), 7 of whom (12.7%) demonstrated a subsequent PSA decline >= 50%. A longer duration of primary androgen deprivation therapy and total duration of all previous hormonal therapies was associated with a longer time to progression with LDK (P <.05). The most common reversible adverse effect of LDK was NCI Common Toxicity Criteria Grade I or 2 fatigue (12.3%). CONCLUSIONS. LDK is associated with a PSA response rate comparable to HDK as secondary hormonal therapy in patients with AIPC, but with less toxicity. Although uncommon, additional durable responses occurred in some patients after dose escalation. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 26 TC 35 Z9 37 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2006 VL 107 IS 5 BP 975 EP 981 DI 10.1002/cncr.22085 PG 7 WC Oncology SC Oncology GA 077TV UT WOS:000240054200011 PM 16862573 ER PT J AU Shurin, MR Shurin, GV Lokshin, A Yurkovetsky, ZR Gutkin, DW Chatta, G Zhong, H Han, BH Ferris, RL AF Shurin, Michael R. Shurin, Galina V. Lokshin, Anna Yurkovetsky, Zoya R. Gutkin, Dmitry W. Chatta, Gurkamal Zhong, Hua Han, Baohui Ferris, Robert L. TI Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic cells: friends or enemies? SO CANCER AND METASTASIS REVIEWS LA English DT Review DE intratumoral cytokines; chemokines; growth factors; dendritic cells; immunosuppression ID ENDOTHELIAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; ANTIGEN-PRESENTING CELLS; CD4(+) T-CELLS; CHEMOATTRACTANT PROTEIN-1 EXPRESSION; METASTATIC CANCER-PATIENTS; CHEMOKINE RECEPTOR CXCR4; CYTOKINE MESSENGER-RNA; DRAINING LYMPH-NODES AB The tumor microenvironment consists of a variable combination of tumor cells, stromal fibroblasts, endothelial cells and infiltrating leukocytes, such as macrophages, T lymphocytes, and dendritic cells. A variety of cytokines, chemokines and growth factors are produced in the local tumor environment by different cells accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of multiple cell types. The interaction between cytokines, chemokines, growth factors and their receptors forms a comprehensive network at the tumor site, which is primary responsible for overall tumor progression and spreading or induction of antitumor immune responses and tumor rejection. Although the general thought is that dendritic cells are among the first cells migrating to the tumor site and recognizing tumor cells for the induction of specific antitumor immunity, the clinical relevance of dendritic cells at the site of the tumor remains a matter of debate regarding their role in the generation of successful antitumor immune responses in human cancers. While several lines of evidence suggest that intratumoral dendritic cells play an important role in antitumor immune responses, understanding the mechanisms of dendritic cell/tumor cell interaction and modulation of activity and function of different dendritic cell subtypes at the tumor site is incomplete. This review is limited to discussing the role of intratumoral cytokine network in the understanding immunobiology of tumor-associated dendritic cells, which seems to possess different regulatory functions at the tumor site. C1 Shanghai Chest Hosp, Shanghai, Peoples R China. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh Med Ctr, Dept Otolaryngol, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Shurin, MR (reprint author), 5725 CHP MT,200 Lothrop St, Pittsburgh, PA 15213 USA. EM shurinmr@upmc.edu FU NCI NIH HHS [1R01 CA115902, 2R01 CA084270] NR 254 TC 73 Z9 88 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD SEP PY 2006 VL 25 IS 3 BP 333 EP 356 DI 10.1007/s10555-006-9010-6 PG 24 WC Oncology SC Oncology GA 114HK UT WOS:000242657100006 PM 17029028 ER PT J AU Greenberg, RA AF Greenberg, Roger A. TI BRCA mutations and childhood cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE BRCA1; BRCA2; Fanconi anemia; childhood cancer; breast cancer ID CARRIERS C1 Univ Penn, Sch Med, Abramson Family Canc Ctr Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. RP Greenberg, RA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way,Smith 814, Boston, MA 02115 USA. EM rgreenberg@partners.org FU NCI NIH HHS [K08 CA106597, K08 CA106597-01A2] NR 6 TC 2 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP PY 2006 VL 5 IS 9 BP 1103 EP 1104 DI 10.4161/cbt.5.9.3370 PG 2 WC Oncology SC Oncology GA 117CE UT WOS:000242849500021 PM 17012842 ER PT J AU Laden, F Hart, JE Eschenroeder, A Smith, TJ Garshick, E AF Laden, Francine Hart, Jaime E. Eschenroeder, Alan Smith, Thomas J. Garshick, Eric TI Historical estimation of diesel exhaust exposure in a cohort study of US railroad workers and lung cancer SO CANCER CAUSES & CONTROL LA English DT Article DE diesel exhaust; lung cancer; occupational exposure; emission factors ID AIR-POLLUTION; MORTALITY AB We have previously shown an elevated risk of lung cancer mortality in diesel exhaust exposed railroad workers. To reduce exposure misclassification, we obtained extensive historical information on diesel locomotives used by each railroad. Starting in 1945, we calculated the rate each railroad converted from steam to diesel, creating annual railroad-specific weighting factors for the probability of diesel exposure. We also estimated the average annual exposure intensity based on emission factors. The U.S. Railroad Retirement Board provided railroad assignment and work histories for 52,812 workers hired between 1939-1949, for whom we ascertained mortality from 1959-1996. Among workers hired after 1945, as diesel locomotives were introduced, the relative risk of lung cancer for any exposure was 1.77 (95% CI = 1.50-2.09), and there was evidence of an exposure-response relationship with exposure duration. Exposed workers hired before 1945 had a relative risk of 1.30 (95% CI = 1.19-1.43) for any exposure and there was no evidence of a dose response with duration. There was no evidence of increasing risk using estimated measures of intensity although the overall lung cancer risk remained elevated. In conclusion, although precise historical estimates of exposure are not available, weighting factors helped better define the exposure-response relationship of diesel exhaust with lung cancer mortality. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Alanova Inc, Lincoln, MA USA. Vet Affairs Boston Healthcare, Pulm & Crit Care Med Sect, Med Serv, Boston, MA USA. RP Laden, F (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM Francine.laden@channing.harvard.edu FU NCI NIH HHS [CA79725, R01 CA079725]; PHS HHS [CCR115818] NR 20 TC 24 Z9 25 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2006 VL 17 IS 7 BP 911 EP 919 DI 10.1007/s10552-006-0027-5 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 063SO UT WOS:000239040100005 PM 16841258 ER PT J AU Skinner, HG Michaud, DS Giovannucci, E Willett, WC Colditz, GA Fuchs, CS AF Skinner, Halcyon G. Michaud, Dominique S. Giovannucci, Edward Willett, Walter C. Colditz, Graham A. Fuchs, Charles S. TI Vitamin D intake and the risk for pancreatic cancer in two cohort studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PHYSICAL-ACTIVITY QUESTIONNAIRE; FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; PROSTATE-CANCER; D ANALOGS; ULTRAVIOLET-RADIATION; DIETARY QUESTIONNAIRE; DIABETES-MELLITUS; COLON CANCER; HUMAN-SKIN AB Vitamin D and its analogues exhibit potent antitumor effects in many tissues, including the pancreas. Normal and malignant pancreatic tissues were recently shown to express high levels of vitamin D 1-alpha-hydroxylase, which converts circulating 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. We examined associations between dietary intake of vitamin D, calcium, and retinol and subsequent risk for pancreatic cancer. We conducted prospective studies in cohorts of 46,771 men ages 40 to 75 years as of 1986 (the Health Professionals Follow-up Study), and 75,427 women ages 38 to 65 years as of 1984 (the Nurses' Health Study), documenting incident pancreatic cancer through the year 2000. Diet was ascertained by semiquantitative food-frequency questionnaire. We identified 365 incident cases of pancreatic cancer over 16 years of follow-up. Compared with participants in the lowest category of total vitamin D intake (< 150 IU/d), pooled multivariate relative risks for pancreatic cancer were 0.78 [95% confidence interval (95% CI), 0.59-1.01] for 150 to 299 IU/d, 0.57 (95% CI, 0.40-0.83) for 300 to 449 IU/d, 0.56 (95% CI, 0.36-0.87) for 450 to 599 IU/d, and 0.59 (95% CI, 0.40-0.88) for >= 600 IU/d (P-trend = 0.01). These associations may be stronger in men than women. After adjusting for vitamin D intake, calcium and retinol intakes were not associated with pancreatic cancer risk. In two U.S. cohorts, higher intakes of vitamin D were associated with lower risks for pancreatic cancer. Our results point to a potential role for vitamin D in the pathogenesis and prevention of pancreatic cancer. C1 Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Skinner, HG (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM hskinner@northwestern.edu RI Skinner, Halcyon/A-1049-2009; zhao, yanrong/D-1885-2013; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI zhao, yanrong/0000-0002-0627-6003; Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA109361, CA55075, CA86102, CA87969] NR 43 TC 93 Z9 98 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2006 VL 15 IS 9 BP 1688 EP 1695 DI 10.1158/1055-9965.EPI-06-0206 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 085FB UT WOS:000240587800021 PM 16985031 ER PT J AU Cornetta, K Croop, J Dropcho, E Abonour, R Kieran, MW Kreissman, S Reeves, L Erickson, LC Williams, DA AF Cornetta, K. Croop, J. Dropcho, E. Abonour, R. Kieran, M. W. Kreissman, S. Reeves, L. Erickson, L. C. Williams, D. A. TI A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with O6-methylguanine DNA methyltransferase SO CANCER GENE THERAPY LA English DT Article DE methylguanine DNA methyltransferase; retroviral gene transfer; brain tumors; clinical trial ID HEMATOPOIETIC STEM-CELLS; DRUG-RESISTANCE GENES; IN-VIVO SELECTION; CHLOROETHYLNITROSOUREA TREATMENT; PROGENITOR CELLS; FRAGMENT CH-296; CHEMOTHERAPY; THERAPY; CANCER; MICE AB Administration of chemotherapy is often limited by myelosuppression. Expression of drug-resistance genes in hematopoietic cells has been proposed as a means to decrease the toxicity of cytotoxic agents. In this pilot study, we utilized a retroviral vector expressing methylguanine DNA methyltransferase (MGMT) to transduce hematopoietic progenitors, which were subsequently used in the setting of alkylator therapy (procarbazine, CCNU, vincristine (PCV)) for poor prognosis brain tumors. Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells were collected by apheresis and enriched for CD34+ expression. Nine subjects were infused with CD34+-enriched cells treated in a transduction procedure involving a 4-day exposure to cytokines with vector exposure on days 3 and 4. No major adverse event was related to the gene therapy procedure. Importantly, the engraftment kinetics of the treated product was similar to unmanipulated peripheral blood stem cells, suggesting that the ex vivo manipulation did not significantly reduce engrafting progenitor cell function. Gene-transduced cells were detected in all subjects. Although the level and duration was limited, patients receiving cells transduced using fibronectin 'preloaded' with virus supernatant appeared to show improved in vivo marking frequency. These findings demonstrate the feasibility and safety of utilizing MGMT-transduced CD34+ peripheral blood progenitor cells in the setting of chemotherapy. C1 Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Duke Univ, Dept Pediat, Durham, NC 27706 USA. Cincinnati Childrens Res Fdn, Div Expt Hematol, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Indiana Univ, Sch Med, Dept Pharmacol, Indianapolis, IN 46202 USA. RP Cornetta, K (reprint author), Indiana Univ, Sch Med, Dept Med & Mol Genet, IB 130,975 W Walnut St, Indianapolis, IN 46202 USA. EM kcornett@iupui.edu OI Kieran, Mark/0000-0003-2184-7692 NR 38 TC 12 Z9 15 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP PY 2006 VL 13 IS 9 BP 886 EP 895 DI 10.1038/sj.cgt.7700963 PG 10 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 074MT UT WOS:000239817200007 PM 16645619 ER PT J AU Perner, S Demichelis, F Beroukhim, R Schmidt, FH Mosquera, JM Setlur, S Tchinda, J Tomlins, SA Hofer, MD Pienta, KG Kuefer, R Vessella, R Sun, XW Meyerson, M Lee, C Sellers, WR Chinnaiyan, AM Rubin, MA AF Perner, Sven Demichelis, Francesca Beroukhim, Rameen Schmidt, Folke H. Mosquera, Juan-Miguel Setlur, Sunita Tchinda, Joelle Tomlins, Scott A. Hofer, Matthias D. Pienta, Kenneth G. Kuefer, Rainer Vessella, Robert Sun, Xiao-Wei Meyerson, Matthew Lee, Charles Sellers, William R. Chinnaiyan, Arul M. Rubin, Mark A. TI TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; EXPRESSION; MODEL; OVEREXPRESSION; CELLS; GENE; DNA AB Prostate cancer is a common and clinically heterogeneous disease with marked variability in progression. The recent identification of gene fusions of the 5'-untransiated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members, either ERG (21q22.2), ETVI (7p21.2), or ETV4 (17q21), suggests a mechanism for overexpression of the ETS genes in the majority of prostate cancers. In the current study using fluorescence in situ hybridization (FISH), we identified the TMPRSS2:ERG rearrangements in 49.2% of 118 primary prostate cancers and 41.2% of IS hormone-naive lymph node metastases. The FISH assay detected intronic deletions between ERG and TMPRSS2 resulting in TMPRSS2:ERG fusion in 60.3% (35 of 58) of the primary TMPRSS2:ERG prostate cancers and 42.9% (3 of 7) of the TMPRSS2:ERG hormone-naive lymph node metastases. A significant association was observed between TMPRSS2:ERG rearranged tumors through deletions and higher tumor stage and the presence of metastatic disease involving pelvic lymph nodes. Using 100K oligonucleotide single nucleotide polymorphism arrays, a homogeneous deletion site between ERG and TMPRSS2 on chromosome 21q22.2-3 was identified with two distinct subclasses distinguished by the start point of the deletion at either 38.765 or 38.911 Mb. This study confirms that TMPRSS2:ERG,TMPRSS2:ERG is fused in approximately half of the prostate cancers through deletion of genomic DNA between ERG and TMPRSS2. The deletion as cause of TMPRSS2:ERG fusion is associated,with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Ulm, Dept Pathol, Ulm, Germany. Univ Hosp Ulm, Dept Urol, Ulm, Germany. ITCirst, SRA Div, Bioinformat Grp, Trento, Italy. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02138 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med Oncol, Ann Arbor, MI 48109 USA. Univ Washington, Seattle, WA 98195 USA. RP Rubin, MA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, EBRC 442A,221 Longwood Ave, Boston, MA 02115 USA. EM marubin@partners.org RI Meyerson, Matthew/E-7123-2012; Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU NCI NIH HHS [P50 CA090381, P50 CA097186, P50 CA69568, R01CA109038, T32 CA009172]; NIA NIH HHS [R01AG21404] NR 20 TC 319 Z9 332 U1 3 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8337 EP 8341 DI 10.1158/0008-5472.CAN-06-1482 PG 5 WC Oncology SC Oncology GA 081PL UT WOS:000240329400004 PM 16951139 ER PT J AU Wang, JH Cai, Y Ren, CX Ittmann, M AF Wang, Jianghua Cai, Yi Ren, Chengxi Ittmann, Mchael TI Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer SO CANCER RESEARCH LA English DT Article ID RADICAL PROSTATECTOMY; SERINE-PROTEASE; GENE; PROGRESSION AB Recent studies have reported that the majority of prostate cancers express fusion genes in which the 5' region of the androgen-regulated TMPRSS2 gene is fused to an ETS family transcription factor, most commonly the ERG gene. We have characterized in detail the expression of TMPRSS2/ERG fusion mRNAs and correlated the isoforms expressed and expression levels with clinical outcome in cancers from men undergoing radical prostatectomy. Overall, 59% of clinically localized prostate cancers express the TMPRSS2/ERG fusion gene, confirming the initial observations of high frequency expression of this fusion mRNA in prostate cancer. There was significant variation in the alternatively spliced isoforms expressed in different cancers. Expression of an isoform, in which the native ATG in exon 2 of the TMPRSS2 gene is in frame with exon 4 of the ERG gene, was associated with clinical and pathologic variables of aggressive disease. Expression of other isoforms, in which the native ERG ATG in exon 3 was the first in-frame ATG, was associated with seminal vesicle invasion, which is correlated with poor outcome following radical prostatectomy. Cancers not expressing these isoforms tended to express higher levels of fusion mRNAs, and in this group, higher expression levels of fusion mRNA were present in cancers with early prostate-specific antigen recurrence. Thus, both the isoforms of TMPRSS2/ERG fusions expressed and expression level may affect prostate cancer progression. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Pl, Houston, TX 77030 USA. EM mittmann@bcm.tme.edu FU NCI NIH HHS [P50CA058204] NR 16 TC 250 Z9 260 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8347 EP 8351 DI 10.1158/0008-5472.CAN-06-1966 PG 5 WC Oncology SC Oncology GA 081PL UT WOS:000240329400006 PM 16951141 ER PT J AU Gerweck, LE Vijayappa, S Kurimasa, A Ogawa, K Chen, DJ AF Gerweck, Leo E. Vijayappa, Shashirekha Kurimasa, Akihiro Ogawa, Kazuhiko Chen, David J. TI Tumor cell radiosensitivity is a major determinant of tumor response to radiation SO CANCER RESEARCH LA English DT Article ID SENSITIVITY AB Substantial evidence suggests that the radiosensitivity of the tumor cells is the primary determinant of tumor response to radiation. More recent studies suggest that tumor stroma radiosensitivity is the principle determinant of response. To assess the relationship between intrinsic tumor cell radiosensitivity and tumor response, we altered the intrinsic radiosensitivity of a cloned tumor cell line and analyzed the effect of this alteration on tumor response. A cloned tumor cell line derived from DNA double-strand break repair-deficient severe combined immunodeficient mice was transfected with the double-strand break repair gene DNA-PKcs. The intrinsic radiosensitivity of the transfected tumor line was decreased by a factor of similar to 1.5. The isogenic lines were used to initiate tumors in NCr-nu/nu mice. When transplanted in the same strain of mice and exposed to the same dose of radiation, the isogenic tumors may be expected to exhibit a similar response to radiation if radiation damage to host stroma is the principle determinant of response. This was not observed. Over the dose range of 20 Gy in four 5-Gy fractions to a single dose of 30 Gy, the 1.5-fold increase in intrinsic tumor cell radioresistance conferred by the introduction of DNA-PKcs caused a 1.5-fold decrease in tumor growth delay. The results show that the intrinsic radiosensitivity of tumor cells is a major determinant of tumor response to radiation. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Tottori Univ, Dept Genet Med & Regenerat Therapeut, Tottori 680, Japan. Univ Texas, SW Med Ctr, Dept Radiat Oncol, Div Mol Radiat Oncol, Dallas, TX USA. RP Gerweck, LE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM lgerweck@partners.org FU NCI NIH HHS [CA092366, CA50519] NR 7 TC 47 Z9 50 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8352 EP 8355 DI 10.1158/0008-5472.CAN-06-0533 PG 4 WC Oncology SC Oncology GA 081PL UT WOS:000240329400007 PM 16951142 ER PT J AU Priolo, C Tang, D Brahamandan, M Benassi, B Sicinska, E Ogino, S Farsetti, A Porrello, A Finn, S Zimmermann, J Febbo, P Loda, M AF Priolo, Carmen Tang, Dan Brahamandan, Mohan Benassi, Barbara Sicinska, Ewa Ogino, Shuji Farsetti, Antonella Porrello, Alessandro Finn, Stephen Zimmermann, Johann Febbo, Phillip Loda, Massimo TI The isopeptidase USP2a protects human prostate cancer from apoptosis SO CANCER RESEARCH LA English DT Article ID FATTY-ACID SYNTHASE; RECEPTOR TYROSINE KINASES; NF-KAPPA-B; DEUBIQUITINATING ENZYMES; ANDROGEN-INDEPENDENCE; EXPRESSION; UNP; HAUSP; CELLS; P53 AB Deubiquitinating enzymes can prevent the destruction of protein substrates prior to proteasomal degradation. The ubiquitin-specific protease 2a (USP2a) deubiquitinates the antiapoptotic proteins Fatty Acid Synthase and Mdm2. Here, we show that when USP2a is overexpressed in nontransformed cells, it exhibits oncogenic behavior both in vitro and in vivo and prevents apoptosis induced by chemotherapeutic agents. Notably, USP2a silencing in several human cancer cell lines results in apoptosis. Gene set enrichment analysis, which focuses on groups of genes sharing biological function or regulatory pathways, was done on microarray expression data from human prostate cancers. The cell death-related gene set, as well as a selected cluster of validated p53 target genes, were significantly enriched in the low USP2a expression group of tumors. Conversely, genes implicated in fatty acid metabolism were significantly associated with tumors expressing high USP2a (44%). The expression profile analysis is consistent with the effects of USP2a on its known targets, i.e., Fatty Acid Synthase and Mdm2, defining a subset of prostate tumors resistant to apoptosis. USP2a thus represents a therapeutic target in prostate cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Novartis Pharma, Oncol Res, Basel, Switzerland. Duke Univ, Inst Genome Sci & Policy, Durham, NC USA. Regina Elena Inst Canc Res, Dept Med Oncol, Rome, Italy. Regina Elena Inst Canc Res, Dept Expt Oncol, Rome, Italy. Catholic Univ Rome, Rome, Italy. CNR, INeMM, Rome, Italy. RP Loda, M (reprint author), Dana Farber Canc Inst, D1536,44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu OI Finn, Stephen/0000-0002-8628-5814 FU NCI NIH HHS [5P50CA90381, P01 CA089021] NR 45 TC 70 Z9 74 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8625 EP 8632 DI 10.1158/0008-5472.CAN-06-1374 PG 8 WC Oncology SC Oncology GA 081PL UT WOS:000240329400041 PM 16951176 ER PT J AU Hatton, BA Knoepfler, PS Kenney, AM Rowitch, DH de Alboran, IM Olson, JM Eisenman, RN AF Hatton, Beryl A. Knoepfler, Paul S. Kenney, Anna Marie Rowitch, David H. de Alboran, Ignacio Moreno Olson, James M. Eisenman, Robert N. TI N-myc is an essential downstream effector of Shh signaling during both normal and neoplastic cerebellar growth SO CANCER RESEARCH LA English DT Article ID PRIMITIVE NEUROECTODERMAL TUMORS; CELL-CYCLE PROGRESSION; CENTRAL-NERVOUS-SYSTEM; SONIC-HEDGEHOG; NEURONAL PRECURSORS; PROLIFERATION; MUTATIONS; MEDULLOBLASTOMA; EXPRESSION; PROMOTES AB We examined the genetic requirements for the Myc family of oncogenes in normal Sonic hedgehog (Shh)-mediated cerebellar granule neuronal precursor (GNP) expansion and in Shh pathway-induced medulloblastoma formation. In GNP-enriched cultures derived from N-myc(F1/F1) and c-myc(F1/F1) mice, disruption of N-myc, but not c-myc, inhibited the proliferative response to Shh. Conditional deletion of c-myc revealed that, although it is necessary for the general regulation of brain growth, it is less important for cerebellar development and GNP expansion than N-myc. In vivo analysis of compound mutants carrying the conditional N-myc null and the activated Smoothened (ND2:SmoA1) alleles showed, that although granule cells expressing the ND2:SmoA1 transgene are present in the N-myc null cerebellum, no hyperproliferation or tumor formation was detected. Taken together, these findings provide in vivo evidence that N-myc acts downstream of Shh/Smo signaling during GNP proliferation and that N-myc is required for medulloblastoma genesis even in the presence of constitutively active signaling from the Shh pathway. C1 Univ Washington, Grad Program Mol & Cell Biol, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Div Basic Sci, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Div Clin Res, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Div Pediat Oncol, Childrens Hosp, Seattle, WA 98195 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Natl Biotechnol Ctr, Dept Immunol & Oncol, Madrid, Spain. RP Hatton, BA (reprint author), Univ Washington, Grad Program Mol & Cell Biol, Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,Mailstop D4-100,POB 19024, Seattle, WA 98109 USA. EM berylh@u.washington.edu FU NCI NIH HHS [CA20525, CA112350-01, CA114400-01] NR 33 TC 91 Z9 94 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8655 EP 8661 DI 10.1158/0008-5472.CAN-06-1621 PG 7 WC Oncology SC Oncology GA 081PL UT WOS:000240329400045 PM 16951180 ER PT J AU Sathornsumetee, S Hjelmeland, AB Keir, ST McLendon, RE Batt, D Ramsey, T Yusuff, N Rasheed, BKA Kieran, MW Laforme, A Bigner, DD Friedman, HS Rich, JN AF Sathornsumetee, Sith Hjelmeland, Anita B. Keir, Stephen T. McLendon, Roger E. Batt, David Ramsey, Timothy Yusuff, Naeem Rasheed, B. K. Ahmed Kieran, Mark W. Laforme, Andrea Bigner, Darell D. Friedman, Henry S. Rich, Jeremy N. TI AAL881, a novel small molecule inhibitor of RAF and vascular endothelial growth factor receptor activities, blocks the growth of malignant glioma SO CANCER RESEARCH LA English DT Article ID FARNESYLTRANSFERASE INHIBITOR; TYROSINE KINASES; CELL-LINES; THERAPEUTIC STRATEGY; MUTATION ANALYSIS; IN-VIVO; TUMORS; ANGIOGENESIS; ACTIVATION; EXPRESSION AB Malignant gliomas are highly proliferative and angiogenic cancers resistant to conventional therapies. Although RAS and RAF mutations are uncommon in gliomas, RAS activity is increased in gliomas. Additionally, vascular endothelial growth factor and its cognate receptors are highly expressed in gliomas. We now report that AAL881, a novel low-molecular weight inhibitor of the kinase activities associated with B-RAF, C-RAF (RAF-1), and VEGF receptor-2 (VEGFR2), showed activity against glioma cell lines and xenografts. In culture, AAL881 inhibited the downstream effectors of RAF in a concentration-dependent manner, with inhibition of proliferation associated with a G, cell cycle arrest, induction of apoptosis, and decreased colony formation. AAL881 decreased the proliferation of bovine aortic endothelial cells as well as the tumor cell secretion of vascular endothelial growth factor and inhibited the invasion of glioma cells through an artificial extracellular matrix. Orally administered AAL881 was well tolerated with minimal weight loss in non-tumor-bearing mice. Established s.c. human malignant glioma xenografts grown in immunocompromised mice treated with a 10-day course of oral AAL881 exhibited growth delays relative to control tumors, frequently resulting in long-term complete regressions. AAL881 treatment extended the survival of immunocompromised mice bearing orthotopic glioma xenografts compared with placebo controls. The intraparenchymal portions of orthotopic AAL881-treated tumors underwent widespread necrosis consistent with vascular disruption compared with the subarachnoid elements. These effects are distinct from our prior experience with VEGFR2 inhibitors, suggesting that targeting RAF itself or in combination with VEGFR2 induces profound tumor responses in gliomas and may serve as a novel therapeutic approach in patients with malignant gliomas. C1 Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Novartis Inst Biomed Res, Cambridge, MA USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP Rich, JN (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Dept Surg, Box 2900, Durham, NC 27710 USA. EM rich0001@mc.duke.edu OI Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [1 P20 CA096890, 1 P50 CA 108786, CA11898]; NCRR NIH HHS [M01 RR 30]; NINDS NIH HHS [NS047409, NS054276, NS20023] NR 42 TC 41 Z9 42 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2006 VL 66 IS 17 BP 8722 EP 8730 DI 10.1158/0008-5472.CAN-06-0284 PG 9 WC Oncology SC Oncology GA 081PL UT WOS:000240329400053 PM 16951188 ER PT J AU Jurisicova, A Lee, HJ D'Estaing, SG Tilly, J Perez, GI AF Jurisicova, A. Lee, H. -J D'Estaing, S. G. Tilly, J. Perez, G. I. TI Molecular requirements for doxorubicin-mediated death in murine oocytes SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE oocyte; doxorubicin; apoptosis; gene expression; sphingolipids ID PREIMPLANTATION EMBRYO DEVELOPMENT; ANTHRACYCLINE ANTITUMOR DRUGS; RESISTANT CELL-LINES; MITOCHONDRIAL-MEMBRANE; SIGNALING PATHWAYS; MOUSE ZYGOTES; APOPTOSIS; FRAGMENTATION; GENE; LOCALIZATION AB We previously published evidence that oocytes exposed to doxorubicin (DXR), a widely used chemotherapeutic agent, rapidly undergo morphological and biochemical changes via discrete effector signaling pathways consistent with the occurrence of apoptosis. In this report, we elucidated the molecular requirements for actions of this drug in oocytes. Our results indicate that within 1 h of exposure DXR causes rapid DNA damage, and commits the oocyte to cytoplasmic fragmentation by the fourth hour, followed by delayed oocyte activation and execution of cytoplasmic fragmentation. Inhibitors that interfere with oocyte activation consistently rescue cytoplasmic fragmentation, but fail to suppress DNA damage. There was evidence of depletion of Bax, Caspase-2, MA-3 and Bcl-x transcripts, suggesting that modulations by DXR caused recruitment of these maternal transcripts into the translation process. Furthermore, sphingolipids such as sphingosine-1-phosphate and ceramide modulate DXR actions by, respectively, altering its intracellular trafficking, or by sustaining the drug's contact with DNA. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Physiol, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5G 1X5, Canada. RP Perez, GI (reprint author), Michigan State Univ, Dept Physiol, 4173 BPS, E Lansing, MI 48824 USA. EM perezg@msu.edu RI Jurisicova, Andrea/E-4580-2013 FU NICHD NIH HHS [R01-HD34226] NR 40 TC 43 Z9 43 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 2006 VL 13 IS 9 BP 1466 EP 1474 DI 10.1038/sj.cdd.4401819 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 075XL UT WOS:000239920600005 PM 16439991 ER PT J AU Fan, Z Zhang, H Zhang, Q AF Fan, Z. Zhang, H. Zhang, Q. TI Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE pp32; growth inhibition; histone H3 acetylation; histone H3 phosphorylation; transcription; apoptosis ID NUCLEOSOME ASSEMBLY PROTEIN; EARLY GENE INDUCTION; GRANZYME-A; NUCLEAR PHOSPHOPROTEIN; PROSTATE-CANCER; IDENTIFICATION; DEATH; SET; STIMULATION; ACTIVATION AB pp32 belongs to a family of leucine-rich acidic nuclear proteins, which play important roles in many cellular processes including regulation of chromatin remodeling, transcription, RNA transport, transformation and apoptosis. pp32 is described as a new tumor suppressor. It is unknown as to how pp32 works in tumor suppression. We found that overexpression of pp32 in human Jurkat T cells inhibits cell growth, and silenced pp32 promotes growth. We first showed that hyperacetylation and hyperphosphorylation of histone H3 are required for T-cell activation. Phosphorylation of histone H3 precedes acetylation during T-cell activation. pp32 specifically binds to histone H3 and blocks its acetylation and phosphorylation. pp32 directly initiates caspase activity and also promotes granzyme A-mediated caspase-independent cell death. Taken together, pp32 plays a repressive role by inhibiting transcription and triggering apoptosis. C1 Chinese Acad Sci, Natl Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China. Chinese Acad Sci, Ctr Infect Immun, Inst Biophys, Beijing 100101, Peoples R China. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Fan, Z (reprint author), Chinese Acad Sci, Natl Lab Biomacromol, Inst Biophys, 15 Datun Rd, Beijing 100101, Peoples R China. EM fanz@moon.ibp.ac.cn NR 37 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 2006 VL 13 IS 9 BP 1485 EP 1494 DI 10.1038/sj.cdd.4401825 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 075XL UT WOS:000239920600007 PM 16341127 ER PT J AU He, XM Amin, AA Fowler, A Toner, M AF He, Xiaoming Amin, Arthi A. Fowler, Alex Toner, Mehmet TI Thermally induced introduction of trehalose into primary rat hepatocytes SO CELL PRESERVATION TECHNOLOGY LA English DT Article ID MICROVESSEL ENDOTHELIAL-CELLS; WATER REPLACEMENT HYPOTHESIS; PRESERVING DRY BIOMATERIALS; MAMMALIAN-CELLS; DESICCATION TOLERANCE; INTRACELLULAR TREHALOSE; SANDWICH CONFIGURATION; PERMEABILITY CHANGES; MEMBRANE-PROPERTIES; HUMAN OOCYTES AB Trehalose was introduced into suspended primary rat hepatocytes through pathways resulting from thermally induced alterations of the cellular membrane. The hepatocytes were suspended in a diluted hepatocyte culture medium (medium:dH(2)O = 1:2) with 0.4 M trehalose during thermal treatments. A significant amount of cytoplasmic trehalose (0.07 M) was detected using high-performance liquid chromatography (HPLC) after heating hepatocytes to 39 degrees C for 10 min in trehalose-supplemented medium. High cell viability (approximately 90%) was retained. The cytoplasmic trehalose concentration reached a plateau (approximately 0.16 M) after heating for 1-2 h. However, the cell viability decreased significantly after 30 min of heating (< approximately 72%). It was further found that by repetitive heating between 0 degrees C and 39 degrees C every 10 min for 1 h (0-39 degrees C, 1 h), high cell viability (approximately 83%) could be maintained and a high cytoplasmic trehalose concentration (approximately 0.13 M) could be obtained. The trehalose-laden hepatocytes (0-39 degrees C, 1 h) were cultured in a double-collagen gel sandwich system for 15 days. They retained normal morphology and produced a normal distribution of F-actin filaments. Furthermore, the hepatospecific functions of urea production and albumin synthesis were similar to those of control hepatocytes kept in fresh medium on ice for one hour. In short, trehalose can be introduced effectively into primary rat hepatocytes by challenging the cells with super-zero to mild hyperthermic (39 degrees C) temperatures. Future studies will focus on the development of effective protocols for both cryopreservation and lyopreservation of trehalose-laden hepatocytes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02114 USA. Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu RI He, Xiaoming/C-5499-2008 OI He, Xiaoming/0000-0003-0125-6086 NR 50 TC 6 Z9 6 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PD FAL PY 2006 VL 4 IS 3 BP 178 EP 187 DI 10.1089/cpt.2006.4.178 PG 10 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 106OE UT WOS:000242109500005 ER PT J AU Righart, R de Gelder, B AF Righart, Ruthger de Gelder, Beatrice TI Context influences early perceptual analysis of faces - An electrophysiological study SO CEREBRAL CORTEX LA English DT Article DE affective pictures; context effects; facial expressions; N170; P1; threatening scenes ID EVENT-RELATED POTENTIALS; SELECTIVE ATTENTION; FACIAL EXPRESSIONS; EMOTIONAL STIMULI; SENSITIVE N170; NATURAL SCENES; VISUAL-CORTEX; AMYGDALA; ERP; RECOGNITION AB Electrophysiological and hemodynamic correlates of processing isolated faces have been investigated extensively over the last decade. A question not addressed thus far is whether the visual scene, which normally surrounds a face or a facial expression, has an influence on how the face is processed. Here we investigated this issue by presenting faces in natural contexts and measuring whether the emotional content of the scene influences processing of a facial expression. Event-related potentials were recorded to faces (fearful/neutral) embedded in scene contexts (fearful/neutral) while participants performed an orientation-decision task (face upright or inverted). Two additional experiments were run, one to examine the effects of context that occur without a face and the other to evaluate the effects of faces isolated from contexts. Faces without any context showed the largest N170 amplitudes. The presence of a face in a fearful context enhances the N170 amplitude over a face in neutral contexts, an effect that is strongest for fearful faces on left occipito-temporal sites. This N170 effect, and the corresponding topographic distribution, was not found for contexts-only, indicating that the increased N170 amplitude results from the combination of face and fearful context. These findings suggest that the context in which a face appears may influence how it is encoded. C1 Tilburg Univ, Dept Psychol, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP de Gelder, B (reprint author), Tilburg Univ, Dept Psychol, Cognit & Affect Neurosci Lab, Warandelaan 2,POB 90153, NL-5000 LE Tilburg, Netherlands. EM B.deGelder@uvt.nl NR 55 TC 90 Z9 95 U1 3 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2006 VL 16 IS 9 BP 1249 EP 1257 DI 10.1093/cercor/bhj066 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 072QV UT WOS:000239689000002 PM 16306325 ER PT J AU Hadjikhani, N Joseph, RM Snyder, J Tager-Flusberg, H AF Hadjikhani, Nouchine Joseph, Robert M. Snyder, Josh Tager-Flusberg, Helen TI Anatomical differences in the mirror neuron system and social cognition network in autism SO CEREBRAL CORTEX LA English DT Review DE autism; cortical thickness; empathy; mirror neuron system ID PERVASIVE DEVELOPMENTAL DISORDERS; MAGNETIC-RESONANCE IMAGES; SUPERIOR TEMPORAL SULCUS; HIGH-FUNCTIONING AUTISM; HEAD CIRCUMFERENCE; ASPERGERS-SYNDROME; CEREBRAL-CORTEX; MOTOR FACILITATION; SPECTRUM DISORDER; BRAIN STRUCTURE AB Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MINIS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Hadjikhani, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 36,1st St,Room 417, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Tager-Flusberg, Helen/D-5265-2009 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NIDCD NIH HHS [P01/U19 DC 03610]; NINDS NIH HHS [R01 NS44824-01] NR 116 TC 265 Z9 279 U1 27 U2 128 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2006 VL 16 IS 9 BP 1276 EP 1282 DI 10.1093/cercor/bh069 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 072QV UT WOS:000239689000005 PM 16306324 ER PT J AU Peterson, RT AF Peterson, Randall T. TI A noncanonical path to mechanism of action SO CHEMISTRY & BIOLOGY LA English DT Editorial Material ID ZEBRAFISH AB Improved methods for discovering small-molecule mechanisms of action are needed. In this issue of Chemistry & Biology, Zhang et al. [1] make clever use of the zebrafish to study the mechanism of the angiogenesis inhibitor fumagillin and reveal that it targets the noncanonical Wnt pathway. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Peterson, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 1eth St, Charlestown, MA 02129 USA. NR 8 TC 4 Z9 5 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD SEP PY 2006 VL 13 IS 9 BP 924 EP 926 DI 10.1016/j.chembiol.2006.09.002 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 091HR UT WOS:000241018400003 PM 16984880 ER PT J AU Huang, Y Wright, CD Merkwan, C Baye, NL Liang, QR Simpson, PC O'Connell, TD AF Huang, Yuan Wright, Casey D. Merkwan, Chastity Baye, Nichole L. Liang, Qiangrong Simpson, Paul C. O'Connell, Timothy D. TI An alpha 1A-adrenergic-ERK signaling pathway mediates survival signaling in cardiac myocytes SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 3rd Annual Symposium of the American-Heart-Association-Council on Basis Cardiovascular Sciences CY JUL 31-AUG 03, 2006 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, AHA Interdisciplinary Working Grp Funct Genom & Translat Biol, Natl Heart, Lung & Blood Inst C1 S Dakota Hlth Rsch Fdn, Sioux Falls, SD USA. San Francisco VA Med Ctr, San Francisco, CA USA. 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 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 1 PY 2006 VL 99 IS 5 BP E25 EP E25 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 079WY UT WOS:000240209800052 ER PT J AU Ramlawi, B Bianchi, C Latham, GL Sodha, NR Boodhwani, M Krosting, J Peltier, H Sellke, FW AF Ramlawi, Basel Bianchi, Cesario Latham, Gary L. Sodha, Neel R. Boodhwani, Munir Krosting, Julie Peltier, Heidi Sellke, Frank W. TI Lack of microRNA regulation in myocardial and skeletal muscle in response to cardioplegic arrest and cardiopulmonary bypass SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 3rd Annual Symposium of the American-Heart-Association-Council on Basis Cardiovascular Sciences CY JUL 31-AUG 03, 2006 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, AHA Interdisciplinary Working Grp Funct Genom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Asuragen Inc, Austin, 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 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 1 PY 2006 VL 99 IS 5 BP E44 EP E44 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 079WY UT WOS:000240209800150 ER PT J AU Franco, V Chen, YF Feng, JA Li, P Wang, D Hasan, E Oparil, S Perry, GJ AF Franco, Veronica Chen, Yiu-Fai Feng, Ji A. Li, Peng Wang, Dajun Hasan, Erum Oparil, Suzanne Perry, Gilbert J. TI Eplerenone prevents adverse cardiac remodelling induced by pressure overload in atrial natriuretic peptide-null mice SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE aldosterone; atrial natriuretic peptide; collagen; extracellular matrix; mineralocorticoid receptor antagonist ID GROWTH-FACTOR-BETA; HEART-FAILURE; ALDOSTERONE PRODUCTION; ESSENTIAL-HYPERTENSION; GENE-EXPRESSION; RAT-HEART; INDEPENDENT ENHANCEMENT; MYOCARDIAL-INFARCTION; ANGIOTENSIN-II; DEFICIENT MICE AB Atrial natriuretic peptide (ANP)-null mice (Nppa(-/-)) exhibit cardiac hypertrophy at baseline and adverse cardiac remodelling in response to transverse aortic constriction (TAC)-induced pressure overload stress. Previous studies have suggested that natriuretic peptides could potentially oppose mineralocorticoid signalling at several levels, including suppression of adrenal aldosterone production, inhibition of mineralocorticoid receptor (MR) activation or suppression of MR-mediated production of pro-inflammatory factors. Thus, we hypothesized that the MR blocker eplerenone would prevent the exaggerated left ventricular (LV) remodelling/fibrosis and dysfunction after TAC in Nppa(-/-). In the present study, Nppa(-/-) and wild-type Nppa(+/+) mice fed eplerenone- or vehicle (oatmeal)-supplemented chow since weaning were subjected to TAC or sham operation. The daily dose of eplerenone administered was approximately 200 mg/kg. At 1 week after TAC, LV size and function were evaluated by echocardiogram and LV cross-sections were stained with picrosirius red for collagen volume measurement. Total RNA was extracted from the LV for real-time polymerase chain reaction analysis of osteopontin. Eplerenone had no effect on baseline hypertrophy observed in sham-operated Nppa(-/-) compared with Nppa(+/+) mice. Eplerenone attenuated the TAC-induced increase in LV weight in both genotypes and completely prevented LV dilation, systolic dysfunction and interstitial collagen deposition seen in Nppa(-/-) mice after TAC. However, serum aldosterone levels were lower in Nppa(-/-) compared with Nppa(+/+) wild types. No interaction between eplerenone and genotype in osteopontin mRNA levels was observed. Eplerenone prevents adverse cardiac remodelling related to pressure overload in ANP-deficient mice, mainly due to an antifibrotic effect. The mechanism whereby ANP deficiency leads to excess hypertrophy, fibrosis and early failure following TAC is increased profibrotic signals resulting from excess or unopposed MR activation, rather than increased levels of aldosterone. C1 Univ Alabama, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Franco, V (reprint author), Univ Alabama, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Zeigler Res Bldg 1024,703 19th St S, Birmingham, AL 35294 USA. EM vfranco@uab.edu RI Franco, Veronica/E-3080-2011 FU NHLBI NIH HHS [HL44195, HL07457] NR 40 TC 8 Z9 9 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD SEP PY 2006 VL 33 IS 9 BP 773 EP 779 DI 10.1111/j.1440-1681.2006.04434.x PG 7 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 072FM UT WOS:000239659300002 PM 16922805 ER PT J AU Kashino, SS Ovendale, P Izzo, A Campos-Neto, A AF Kashino, Suely S. Ovendale, Pamela Izzo, Angelo Campos-Neto, Antonio TI Unique model of dormant infection for tuberculosis vaccine development SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MICROBIAL ENUMERATION TECHNIQUE; MYCOBACTERIUM-TUBERCULOSIS; EXOGENOUS REINFECTION; PROTECTIVE IMMUNITY; TUBERCLE BACILLI; ALPHA-CRYSTALLIN; MOUSE TISSUES; PULMONARY TUBERCULOSIS; EXTRACELLULAR PROTEINS; LATENT TUBERCULOSIS AB Most individuals exposed to Mycobacterium tuberculosis become infected but hinder the infectious process in dormant foci, known as latent tuberculosis. This limited infection usually stimulates strong T-cell responses, which provide lifelong resistance to tuberculosis. However, latent tuberculosis is still poorly understood, particularly because of the lack of a reliable animal model of dormant infection. Here we show that inoculation of mice with a unique streptomycin-auxotrophic mutant of Mycobacterium tuberculosis recapitulates dormant infection. The mutant grows unimpaired in the presence of streptomycin and no longer grows but remains viable for long periods of time after substrate removal, shifting from the log growth phase to the latent stage, as indicated by augmented production of a-crystallin. Mice challenged with the mutant and inoculated with streptomycin for similar to 3 weeks developed a limited infection characterized by a low bacteriological burden and the presence of typical granulomas. After substrate withdrawal, the infection was hindered but few microorganisms remained viable (dormant) in the animals' tissues for at least 6 months. In addition, the animals developed both potent T-cell responses to M. tuberculosis antigens, such as early culture filtrate, Ag85B, and ESAT-6, and resistance to reinfection with virulent M. tuberculosis. Therefore, infection of mice or other animals (e.g., guinea pigs) with M. tuberculosis strain 18b constitutes a simple and attractive animal model for evaluation of antituberculosis vaccines in the context of an M. tuberculosis-presensitized host, a prevailing condition among humans in need of a vaccine. C1 Forsyth Inst, Boston, MA 02115 USA. Corixa Corp, Seattle, WA USA. Colorado State Univ, Ft Collins, CO 80523 USA. RP Campos-Neto, A (reprint author), Forsyth Inst, 140 The Fenway, Boston, MA 02115 USA. EM acampos@forsyth.org RI Kashino, Suely/F-4171-2012; Izzo, Angelo/F-1229-2017 OI Izzo, Angelo/0000-0003-3208-2330 FU NCRR NIH HHS [C06RR11244]; NIAID NIH HHS [AI 43528, R01 AI043528]; PHS HHS [1-A125174] NR 42 TC 11 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD SEP PY 2006 VL 13 IS 9 BP 1014 EP 1021 DI 10.1128/CVI.00120-06 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 085BJ UT WOS:000240577800007 PM 16960113 ER PT J AU Duan, ZF Foster, R Bell, DA Mahoney, J Wolak, K Vaidya, A Hampel, C Lee, H Seiden, MV AF Duan, Zhenfeng Foster, Rosemary Bell, Debra A. Mahoney, Jennifer Wolak, Kathryn Vaidya, Ami Hampel, Constanze Lee, Hang Seiden, Michael V. TI Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SRC TYROSINE KINASE; CELL LUNG-CANCER; PACLITAXEL RESISTANCE; CONSTITUTIVE ACTIVATION; MULTIDRUG-RESISTANCE; CONFERS RESISTANCE; CARCINOMA CELLS; STAT 3; INTERLEUKIN-6; APOPTOSIS AB Purpose: One of the major obstacles in the treatment of ovarian cancer is the development of multidrug resistance. Recent evidence shows that high-grade ovarian cancer often shows activation of the signal transducers and activators of transcription 3 (Stat3) pathway with subsequent transcription of genes that support tumor growth and survival. Less studied is the role of the Stat3 pathway in acquired drug resistance. There is no information on Stat3 expression in chemotherapy naive ovarian cancer as compared with tumors collected later in the natural history of the disease, To further clarify the significance of Stat3 activation in ovarian cancer, here we investigated the Stat3 expression and activation in ovarian cancer and ovarian cancer multidrug resistance cell lines, Experimental Design: Western blotting, electrophoretic mobility shift assay, luciferase assays, ELISA assay, and real-time reverse transcription-PCR determined interleukin-6 and Stat3 pathway expression and activation in cell lines. Stat3 expression in ovarian cancer tissue microarray was evaluated by immunohistochemistry. Results: Activated (phosphorylated) Stat3 is overexpressed in most paclitaxel-resistant ovarian cancer cells. Inhibition of Stat3 activation results in significant decreases in paclitaxel resistance and enhanced apoptosis. Drug-resistant recurrent tumors have significantly greater phosphorylated Stat3 (pStat3) expression as compared with matched primary tumors. Tumors with associated inflammatory cell infiltrates also have a higher proportion of cells staining intensely for nuclear phosphorylated Stat3 as compared with tumors without inflammatory infiltrates, consistent with paracrine activation of the Stat3 pathway by immune-mediated cytokines. Conclusions: These data support the hypothesis that interruption of Stat3 signaling could reverse resistance to paclitaxel and perhaps other chemotherapy agents in human cancer. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. EM zduan@partners.org FU NCI NIH HHS [1K24 CA109416-01A1, 1P50CA105009] NR 41 TC 138 Z9 146 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2006 VL 12 IS 17 BP 5055 EP 5063 DI 10.1158/1078-0432.CCR-06-0861 PG 9 WC Oncology SC Oncology GA 082MX UT WOS:000240392000011 PM 16951221 ER PT J AU Grossman, SA Carson, KA Batchelor, TT Lesser, G Mikkelsen, T Alavi, JB Phuphanich, S Hammour, T Fisher, JD Supko, JG AF Grossman, Stuart A. Carson, Kathryn A. Batchelor, Tracy T. Lesser, Glenn Mikkelsen, Tom Alavi, Jane B. Phuphanich, Surasak Hammour, Tarek Fisher, Joy D. Supko, Jeffrey G. TI The effect of enzyme-inducing antiseizure drugs on the pharmacokinetics and tolerability of procarbazine hydrochloride SO CLINICAL CANCER RESEARCH LA English DT Article ID RECURRENT MALIGNANT GLIOMA; BRAIN-TUMORS; GLIOBLASTOMA-MULTIFORME; PCV-CHEMOTHERAPY; VINCRISTINE PCV; PHASE-II; HYPERSENSITIVITY REACTIONS; ANAPLASTIC ASTROCYTOMA; ADJUVANT CHEMOTHERAPY; HUMAN HEPATOCYTES AB Purpose: Procarbazine hydrochloride (PCB) is one of the few anticancer drugs with activity against high-grade gliomas. This study was conducted to determine if the maximum tolerated dose and pharmacokinetics of PCB are affected by the concurrent use of enzyme-inducing antiseizure drugs (EIASD). Experimental Design: Adults with recurrent high-grade glioma were divided into cohorts who were (+) and were not (-) taking EIASDs. PCB was given orally for 5 consecutive days each month. Six patients were evaluated at each dose level beginning with 200 mg/m(2)/d and escalated using the modified continual reassessment method. Toxicity and response were assessed. Pharmacokinetic studies were done with a new electrospray ionization mass spectrometry assay. Results: Forty-nine patients were evaluated. The maximum tolerated dose was 393 mg/m(2)/d for the +EIASD group and the highest dose evaluated in -EIASD patients was 334 mg/m(2)/d. Myelosuppression was the primary dose-limiting toxicity. Significant hepatic dysfunction occurred in three patients in the +EIASD cohort. Four partial responses (8%) and no complete responses were observed. PCB exhibited linear pharmacokinetics with no significant differences between the two cohorts. A marked increase in peak PCB levels was noted on day 5 relative to day 1, which was not attributable to drug accumulation. Conclusions: This study suggests that (a) EIASD use does not significantly affect the pharmacokinetics of PCB; (b) changes in the peak plasma concentration of PCB, consistent with decreased apparent oral clearance due to autoinhibition of hepatic metabolism, occur with daily closing; and (c) severe hepatic dysfunction may accompany this administration schedule. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Henry Ford Hlth Sci Ctr, Detroit, MI USA. Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Atlanta, GA USA. RP Grossman, SA (reprint author), Johns Hopkins Univ, New Approaches Brain Tumor Therapy Cent Off, Sidney Kimmel Comprehens Canc Ctr, 1550 Orleans St,CRB2-IM-16, Baltimore, MD 21231 USA. EM grossman@jhmi.edu; jfisher@jhmi.edu FU NCI NIH HHS [P30-CA0516, U01-CA62475, U01-CA62406] NR 51 TC 9 Z9 9 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2006 VL 12 IS 17 BP 5174 EP 5181 DI 10.1158/1078-0432.CCR-06-0932 PG 8 WC Oncology SC Oncology GA 082MX UT WOS:000240392000026 PM 16951236 ER PT J AU Rifai, N Gerszten, RE AF Rifai, Nader Gerszten, Robert E. TI Biomarker discovery and validation SO CLINICAL CHEMISTRY LA English DT Editorial Material ID MASS-SPECTROMETRY; PLASMA PROTEOME; LIMITATIONS; DIAGNOSIS C1 Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Rifai, N (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. NR 18 TC 18 Z9 18 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2006 VL 52 IS 9 BP 1635 EP 1637 DI 10.1373/clinchem.2006.074492 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 080XV UT WOS:000240282700002 PM 16940460 ER PT J AU Wolpin, BM Clark, JW Meyerhardt, JA Earle, CC Ryan, DP Enzinger, PC Zhu, AX Blaszkowsky, L Battu, S Fuchs, CS AF Wolpin, Brian M. Clark, Jeffrey W. Meyerhardt, Jeffrey A. Earle, Craig C. Ryan, David P. Enzinger, Peter C. Zhu, Andrew X. Blaszkowsky, Lawrence Battu, Subha Fuchs, Charles S. TI Phase I study of gefitinib plus FOLFIRI in previously untreated patients with metastatic colorectal cancer SO CLINICAL COLORECTAL CANCER LA English DT Article DE chemotherapy; Eastern Cooperative Oncology Group; epidermal growth factor receptor ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; RANDOMIZED-TRIAL; FLUOROURACIL FAILURE; IRINOTECAN; LEUCOVORIN; OXALIPLATIN; EXPRESSION; THERAPY AB Background: In this study, the maximum tolerated dose and toxicity profile of FOLFIRI (infusional fluorouracil [5-FU]/leucovorin/irinotecan) plus gefitinib (an oral inhibitor of the epidermal growth factor receptor) were evaluated as first-line therapy in patients with metastatic colorectal cancer. Patients and Methods: Sixteen patients participated in this study. Oral gefitinib was administered at 250 mg or 500 mg daily in 2 dose-escalation cohorts. FOLFIRI was administered without dose escalation on a 14-day cycle with treatment on day 1 with irinotecan 180 mg/m(2), leucovorin 200 mg/m(2), and 5-FU 400 mg/m(2) bolus, followed by 5-FU 2400 mg/m(2) continuous infusion over 46 hours. Results: The maximum tolerated dose of gefitinib was 250 mg, with diarrhea and neutropenia noted as the principal dose-limiting toxicities. Dose reductions in 5-FU and irinotecan were required in 4 patients because of diarrhea and 1 patient because of neutropenia. A partial response was observed in 25% of patients, and 56% had stable disease for > 12 weeks, corresponding to a disease control rate of 81%. Conclusion: These findings suggest that gefitinib can be safely combined with FOLFIRI as first-line treatment of metastatic CRC and support the safety of further investigations of EGFR tyrosine kinase inhibitors with multiagent chemotherapy in this patient population. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM charles_fuchs@dfci.harvard.edu NR 37 TC 13 Z9 13 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD SEP PY 2006 VL 6 IS 3 BP 208 EP 213 DI 10.3816/CCC.2006.n.037 PG 6 WC Oncology SC Oncology GA 235NM UT WOS:000251241200005 PM 17026790 ER PT J AU Sartor, O Alchalabi, T Figg, WD AF Sartor, Oliver Alchalabi, Tania Douglas Figg, William TI Assessing progress against prostate cancer SO CLINICAL GENITOURINARY CANCER LA English DT Editorial Material C1 Harvard Univ, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RP Sartor, O (reprint author), Harvard Univ, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RI Figg Sr, William/M-2411-2016 NR 4 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2006 VL 5 IS 2 BP 102 EP 103 DI 10.3816/CGC.2006.n.025 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 113TC UT WOS:000242619300001 PM 17026796 ER PT J AU McDermott, DE Regan, MM Atkins, MB AF McDermott, David E. Regan, Meredith M. Atkins, Michael B. TI Inerleukin-2 therapy of mestastatic renal cell cercinoma: Update of phase III trials SO CLINICAL GENITOURINARY CANCER LA English DT Review DE carbonic anhydrase IX; complete remission; cytokine therapy; interferon ID RECOMBINANT HUMAN INTERLEUKIN-2; CARBONIC-ANHYDRASE-IX; ADVANCED CANCER; SUBCUTANEOUS INTERLEUKIN-2; INTERFERON ALPHA-2A; DOSE INTERLEUKIN-2; HOME-THERAPY; CARCINOMA; SURVIVAL; IMMUNOTHERAPY AB High-dose bolus interleukin-2 (IL-2) was granted Food and Drug Administration approval for the treatment of metastatic renal cell carcinoma based on its ability to produce durable responses in a small number of patients. Results from randomized phase III trials suggest that regimens involving lower doses of IL-2 alone or in combination with interferon produce fewer tumor regressions of decreased overall quality. Because of the toxicity and limited efficacy of this treatment, recent studies have focused on identifying predictors of response (or resistance) to IL-2 therapy. This year, investigators will launch a clinical trial designed to prospectively determine whether patients who are more likely to respond to high-dose IL-2 can be identified before therapy is initiated. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Dana Farber Canc Ctr, Renal Canc Program, Boston, MA 02115 USA. RP McDermott, DE (reprint author), Beth Israel Deaconess Med Ctr, Kirstein Room 153,330 Brookline Ave, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU NCI NIH HHS [P50 CA101942-01] NR 43 TC 12 Z9 14 U1 1 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2006 VL 5 IS 2 BP 114 EP 119 DI 10.3816/CGC.2006.n.027 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 113TC UT WOS:000242619300003 PM 17026799 ER PT J AU Fujitani, S Yu, VL AF Fujitani, Shigeki Yu, Victor L. TI Quantitative cultures for diagnosing ventilator-associated pneumonia: A critique SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Serious Infections in the Intensive Care Unit - Pseudomonas Aeruginosa and Acinetobacter Baumannii CY MAY, 2004 CL Univ Pittsburgh Med Ctr, Pittsburg, PA HO Univ Pittsburgh Med Ctr ID PROTECTED SPECIMEN BRUSH; TELESCOPING PLUGGED CATHETERS; PERIPHERAL-BLOOD CULTURES; BRONCHOALVEOLAR LAVAGE; NOSOCOMIAL PNEUMONIA; ENDOTRACHEAL ASPIRATION; BACTERIAL PNEUMONIA; BRONCHOPNEUMONIA; POSITIVITY; ACCURACY AB The diagnosis of ventilator-associated pneumonia has been clouded by uncertainty, because a reference standard has never been established. The use of invasive procedures to obtain respiratory tract samples for culture, with quantitation of the bacteria isolated, has been the approach most commonly advocated. Quantitation of bacteria from lower respiratory tract specimens can be used to distinguish colonization from infection. We review the invasive procedures (bronchoalveolar lavage, protected specimen brushing, nonbronchoscopic bronchoalveolar lavage, and blinded bronchial sampling), the methods of quantitation used, the types of catheters used, the sample collection methods, and the criteria used as cutoffs for the quantitative cultures. Quantitation of lower respiratory tract samples is inherently unstable from a mathematical perspective, given the variability in the volume of fluid instilled and reaspirated and the magnitude and complexity of the area being sampled. We also briefly review the use of quantitation for bacterial infections other than pneumonia, including urinary tract infection and catheter-related bacteremia. The variability in both the methods and reference criteria in the studies reviewed show that the quantitation approach is neither standardized nor evidence based. C1 Vet Adm Med Ctr, Infect Dis Sect, Div Infect Dis, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA USA. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. RP Yu, VL (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Div Infect Dis, Univ Dr C, Pittsburgh, PA 15240 USA. EM vly@pitt.edu NR 51 TC 19 Z9 19 U1 1 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 SEP 1 PY 2006 VL 43 SU 2 BP S106 EP S113 DI 10.1086/504488 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 071TZ UT WOS:000239627100012 PM 16894512 ER PT J AU Newsome, BB McClellan, WM Coffey, CS Allison, JJ Kiefe, CI Warnock, DG AF Newsome, Britt B. McClellan, William M. Coffey, Christopher S. Allison, Jeroan J. Kiefe, Catarina I. Warnock, David G. TI Survival advantage of black patients with kidney disease after acute myocardial infarction SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT Southern Regional Meeting for the Society-for-Clinical-Investigation CY 2005 CL New Orleans, LA SP Soc Clin Invest ID STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; COOPERATIVE CARDIOVASCULAR PROJECT; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; POTENTIAL EXPLANATORY FACTORS; CORONARY HEART-DISEASE; QUALITY-OF-CARE; UNITED-STATES; RACIAL-DIFFERENCES AB Black individuals have a disproportionate incidence of ESRD when compared with white individuals, and among patients with ESRD, black patients experience better survival. The aim of this analysis is to assess, in a nationally representative sample of patients with cardiovascular disease, ethnic differences in survival among predialysis patients with kidney disease. A retrospective cohort analysis was conducted of Cooperative Cardiovascular Project data of Medicare patients who were aged > 65 yr and admitted for incident acute myocardial infarction and had 3 yr of mortality follow-up. Cox regression models and Kaplan Meier estimates were performed to examine differences in survival between black and white patients stratified by severity of kidney disease. Of 57,942 patients, 7.3% were black. Black patients were younger and more likely to be female and were less likely to have decreased kidney function. A significant interaction between race and kidney function existed with respect to mortality among patients who survived to discharge. The adjusted hazard ratios for death, black compared with white patients, were 1.00 (95% confidence interval 0.90 to 1.11) among patients with a GFR >= 60 ml/min per 1.73 m(2) and decreased monotonically among patients with lower GFR to 0.79 (95% confidence interval 0.61 to 0.97) among patients with a GFR 15 to 29 ml/min per 1.73 m(2). Among patients with incident acute myocardial infarction, black patients with more severe kidney disease, when compared with their white counterparts, experience better survival. Further investigation into the reasons for ethnic differences in survival and progression of kidney disease is warranted. C1 Univ Alabama, Ctr Outcomes Effect Res & Educ, Birmingham, AL USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ Alabama, Div Renal Outcomes Res & Epidemiol Sect, Birmingham, AL USA. Univ Alabama, Div Nephrol, Birmingham, AL USA. Univ Alabama, Div Gen Internal Med, Dept Med, Birmingham, AL USA. Univ Alabama, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. Emory Univ, Sch Med, Dept Med, Div Renal, Atlanta, GA 30322 USA. RP Newsome, BB (reprint author), 1530 3rd Ave S,Mt 401E2, Birmingham, AL 35294 USA. EM bnewsome@uab.edu OI Allison, Jeroan/0000-0003-4472-2112 NR 41 TC 23 Z9 23 U1 0 U2 2 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2006 VL 1 IS 5 BP 993 EP 999 DI 10.2215/CJN.01251005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 107LL UT WOS:000242173000016 PM 17699318 ER PT J AU Thadhani, R Tonelli, M AF Thadhani, Ravi Tonelli, Marcello TI Cohort studies: Marching forward SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID POSTMENOPAUSAL HORMONE-THERAPY; KIDNEY-DISEASE; CARDIOVASCULAR-DISEASE; HEMODIALYSIS; MORTALITY; SURVIVAL; DIALYSIS; DESIGN; TRIAL C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Univ Alberta, Div Nephrol, Edmonton, AB, Canada. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Renal Unit, Bullfinch 127, Boston, MA 02114 USA. EM rthadhani@partners.org; mtonelli@ualberta.ca RI Tonelli, Marcello/B-3028-2009 FU NICHD NIH HHS [HD39223]; NIDDK NIH HHS [DK71674] NR 21 TC 42 Z9 42 U1 1 U2 2 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2006 VL 1 IS 5 BP 1117 EP 1123 DI 10.2215/CJN.00080106 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 107LL UT WOS:000242173000032 PM 17699334 ER PT J AU Chertow, GM Palevsky, PM Greene, T AF Chertow, Glenn M. Palevsky, Paul M. Greene, Thomas TI Studying the prevention of acute kidney injury: Lessons from an 18th-century mathematician SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Nephrology CY NOV 08-13, 2005 CL Philadelphia, PA SP Amer Soc Nephrol ID ACUTE-RENAL-FAILURE; RANDOMIZED CONTROLLED-TRIAL; INDUCED NEPHROPATHY; MORTALITY; ACETYLCYSTEINE; INSUFFICIENCY; ANGIOGRAPHY; COSTS C1 Univ Calif San Francisco, Div Nephrol, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Nephrol, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. RP Chertow, GM (reprint author), Univ Calif San Francisco, Dept Med Res, Laurel Heights Suite 430,3333 Calif St, San Francisco, CA 94118 USA. EM chertowg@medicine.ucsf.edu NR 15 TC 26 Z9 26 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2006 VL 1 IS 5 BP 1124 EP 1127 DI 10.2215/CJN.01200406 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 107LL UT WOS:000242173000033 PM 17699335 ER PT J AU Lam, P Berman, S Thurer, R Ashiku, S DeCamp, M Goldstein, M Schumer, S Halmos, B Karp, D Coute, D Bergman, M Boyd-Sirard, C Ou, SH Muzikansky, A Woodard, C Huberman, M AF Lam, Prudence Berman, Stuart Thurer, Robert Ashiku, Simon DeCamp, Malcolm Goldstein, Michael Schumer, Susan Halmos, Balazs Karp, Daniel Coute, Danielle Bergman, Mark Boyd-Sirard, Cynthia Ou, Sai-Hong Muzikansky, Alona Woodard, Cally Huberman, Mark TI Phase II trial of sequential chemotherapy followed by chemoradiation, surgery, and postoperative chemotherapy for the treatment of stage IIIA/IIIB non-small-cell lung cancer SO CLINICAL LUNG CANCER LA English DT Article DE mediastinal staging; multimodality therapy; radiosensitizing; timing of administration ID CARBOPLATIN; PACLITAXEL; RADIOTHERAPY; REGIMENS; THERAPY AB BACKGROUND: The optimal treatment of locally advanced non-small-cell lung cancer remains a challenge. Although the benefit of combined chemoradiation has been established, the optimal chemotherapy regimen, timing of full-dose chemotherapy, and how best to combine chemotherapy with radiation to maximize systemic and radlosensitizing effects remain unclear. PATIENTS AND METHODS: Twenty-nine patients with pathologically confirmed stage IIIA/IIIB non-small-cell lung cancer were included in a phase II trial of sequential carboplatin/ paclitaxel followed by chemoradiation, surgery, and postoperative gemcitabine. Twenty-five patients (86%) completed the concurrent chemotherapy and radiation therapy phase and were eligible for surgery. At restaging, 7 patients (21%) showed disease progression. Seventeen patients (59%) went on to surgery. Few were able to tolerate full postoperative chemotherapy. RESULTS: The 1-year overall survival rate was 61%, with a 2-year survival rate of 56%. Median overall survival was 25.2 months. Seven of the patients are alive and without recurrence at the time of this writing. Our median follow-up time was 22.2 months. Reversible grade 3/4 toxicities were fairly common, experienced in 45% of patients. CONCLUSION: Our results with this combined modality approach are comparable with those of previous, similar studies. Postoperative chemotherapy after initial combined modality therapy is often not feasible, reinforcing the value of initial systemic therapy. Long-term results are still suboptimal and await studies adding targeted therapies to our usual chemotherapy/radiation approaches. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Cambridge Hosp, Dept Hematol Oncol, Cambridge, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Boston, MA 02215 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Div Hematol Oncol, Cleveland, OH 44106 USA. Univ Texas, MD Anderson Canc Ctr, Dv Canc Med, Houston, TX 77030 USA. Minnesota Oncol Hematol PA, Woodbury, MN USA. Genzyme, Cambridge, MA USA. Univ Calif Irvine, Med Ctr, Div Hematol Oncol, Irvine, CA 92717 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Lam, P (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 77 Ave Louis Pasteur,New Res Bldg 1030, Boston, MA 02215 USA. EM plam1@bidmc.harvard.edu NR 16 TC 2 Z9 2 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD SEP PY 2006 VL 8 IS 2 BP 122 EP 129 DI 10.3816/CLC.2006.n.040 PG 8 WC Oncology SC Oncology GA 107LR UT WOS:000242173600006 PM 17026813 ER PT J AU Osipova, D Pekkonen, E Ahveninen, J AF Osipova, Daria Pekkonen, Eero Ahveninen, Jyrki TI Enhanced magnetic auditory steady-state response in early Alzheimer's disease SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Alzheimer's disease; EEG; MEG; auditory steady-state response; ERP; ERF ID MILD COGNITIVE IMPAIRMENT; ENTORHINAL CORTEX; EVOKED-POTENTIALS; SENSORY MEMORY; WHITE-MATTER; DEMENTIA; SCOPOLAMINE; SYSTEM; MODULATION; TRANSIENT AB Objective: Previous studies have reported abnormalities in both spontaneous and evoked electromagnetic brain activity in Alzheimer's disease (AD). We studied the auditory steady-state response (SSR) which represents the net effect of entrained background activity and superimposed cortical evoked responses, in AD patients and healthy controls. Methods: Whole-head magnetoencephalography (MEG) was used to measure SSR to monaural 40-Hz stimulation in AD patients and age-matched controls. Equivalent current dipoles (ECD) of the SSR were modeled in each hemisphere, and source amplitudes were compared between the two groups using time-varying ECD models. Results: Our results indicate that the SSR is significantly increased in AD patients with mild to moderate cognitive deterioration in comparison with healthy elderly subjects. Conclusions: Goal-directed functioning requires optimization of inhibitory and excitatory inputs in the cortex, allowing the adaptation of responsiveness to repetitive stimulation with low relevance. The present results suggest that this balance is impaired in AD, manifesting itself in decreased inhibition in cortical auditory processing and impaired adaptation of the stimulus-locked activity, probably due to abnormalities in cholinergic modulation. Significance: MEG appears to be a sensitive tool to detect abnormalities of auditory processing already in early stages of AD. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, SF-00100 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Ctr Engn, SF-00100 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Neurol, SF-00100 Helsinki, Finland. Helsinki Brain Res Ctr, Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Inst Technol,Athinoula A Martinos, Charlestown, MA USA. RP Osipova, D (reprint author), Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, Fabianinkatu 28, SF-00100 Helsinki, Finland. EM daria.osipova@helsinki.fi OI Pekkonen, Eero/0000-0003-1621-8752 FU NICHD NIH HHS [R01 HD040712] NR 47 TC 19 Z9 19 U1 2 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD SEP PY 2006 VL 117 IS 9 BP 1990 EP 1995 DI 10.1016/j.clinph.2006.05.034 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 097IR UT WOS:000241441200010 PM 16887381 ER PT J AU O'Toole, RV Gobezie, R Hwang, R Chandler, AR Smith, RM Estok, DM Vrahas, MS AF O'Toole, Robert V. Gobezie, Reuben Hwang, Raymond Chandler, Autumn R. Smith, R. Malcolm Estok, Daniel M., II Vrahas, Mark S. TI Low complication rate of LISS for femur fractures adjacent to stable hip or knee arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PERIPROSTHETIC FEMORAL FRACTURES; INVASIVE STABILIZATION SYSTEM; INTERNAL-FIXATION; INDIRECT REDUCTION; PLATE FIXATION; BIOMECHANICAL ANALYSIS; OSTEOSYNTHESIS; CLASSIFICATION; REPLACEMENTS; MULTICENTER AB Fractures of the femur after a knee or hip arthroplasty historically have been plagued with high complication rates. The Less Invasive Stabilization System (LISS) has theoretical advantages of improved biomechanics and limited insult to the bone's vascular supply. We theorized that the LISS would have a lower complication rate than historical controls for these fractures. Patients who were treated with a LISS at two Level I trauma centers from July 2001 to July 2003 were prospectively followed up. The inclusion criteria were an acute fracture of the femur treated with a LISS in a patient with a stable ipsilateral total knee prosthesis and/or hip prosthesis. There were 24 patients in the study group. The injury mechanism was a low-energy fall for all patients. All patients were females with an average age of 79.5 years (range. 64-93 years). Ten patients had ipsilateral hip arthroplasties, nine patients had ipsilateral total knee arthroplasties, and five patients had knee and hip arthroplasties. Followup was at an average of 48 weeks (range, 17-101 weeks). Eighteen of the 19 fractures in the surviving patients with followup healed uneventfully for a complication rate of 5.2%. One fracture was complicated by hardware pullout and was revised to a longer LISS that healed uneventfully. We think our data show that our patients had a low complication rate compared with that of historical controls, and we suggest that the LISS may be an appropriate treatment alternative for femur fractures associated with stable hip or knee prostheses. C1 Univ Maryland, Med Ctr, R Adams Cowley Shock Trauma Ctr, Dept Orthopaed Surg, Baltimore, MD 21201 USA. Harvard Combined Orthopaed Residency Program, Dept Orthopaed Surg, Boston, MA USA. Partners Orthopaed Trauma Program, Dept Orthopaed Surg, Boston, MA USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP O'Toole, RV (reprint author), Univ Maryland Med Syst, Dept Orthopaed Surg, R Adams Cowley Shock Trauma Ctr, Div Orthopaed Traumatol,Off T3R62, 22 GReene St, Baltimore, MD 21201 USA. EM rvo3@yahoo.com NR 59 TC 45 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2006 IS 450 BP 203 EP 210 DI 10.1097/01.blo.0000223987.59702.17 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OH UT WOS:000243021100035 PM 16721350 ER PT J AU Dransfield, MT Bailey, WC AF Dransfield, Mark T. Bailey, William C. TI COPD: Racial disparities in susceptibility, treatment, and outcomes SO CLINICS IN CHEST MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; HOME-OXYGEN-THERAPY; STAGE LUNG-CANCER; GENDER-DIFFERENCES; CHRONIC-BRONCHITIS; AFRICAN-AMERICANS; CIGARETTE-SMOKING; UNITED-STATES; MORTALITY; HEALTH AB Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and mortality continues to increase particularly among African Americans. Although this increase may be caused by changing smoking habits, some studies suggest that African Americans may be more susceptible to tobacco smoke than whites. Unlike other respiratory diseases for which there are significant published data on racial and ethnic disparities in disease outcomes, such information is notably lacking in the COPD literature. This article examines the available data concerning racial disparities in COPD susceptibility and care. C1 Birmingham VA Med Ctr, Pulm Sect, Birmingham, AL 35294 USA. Univ Alabama, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. RP Dransfield, MT (reprint author), Birmingham VA Med Ctr, Pulm Sect, Birmingham, AL 35294 USA. EM mdransfield99@msn.com NR 50 TC 36 Z9 38 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD SEP PY 2006 VL 27 IS 3 BP 463 EP + DI 10.1016/j.ccm.2006.04.005 PG 10 WC Respiratory System SC Respiratory System GA 082WK UT WOS:000240417700009 PM 16880056 ER PT J AU Hofmann, SG Pollack, MH Otto, MW AF Hofmann, Stefan G. Pollack, Mark H. Otto, Michael W. TI Augmentation treatment of psychotherapy for anxiety disorders with D-cycloserine SO CNS DRUG REVIEWS LA English DT Review DE anxiety disorders; augmentation therapy; D-cycloserine; extinction learning; memory enhancement; NMDA receptor agonists ID FEAR-POTENTIATED STARTLE; LONG-TERM POTENTIATION; PLACEBO-CONTROLLED TRIAL; CONDITIONED FEAR; NMDA RECEPTORS; SCHIZOPHRENIC-PATIENTS; ALZHEIMERS-DISEASE; EXTINCTION; AMYGDALA; MEMORY AB Anxiety disorders are among the most common mental disorders. One of the most effective strategies to treat anxiety disorders is exposure therapy with or without cognitive intervention. Fear reduction in exposure therapy is similar to extinction learning. Preclinical studies suggest that extinction learning can be blocked by antagonists at the glutamatergic N-methyl-D-aspartate (NMDA) receptor, and facilitated with D-cycloserine (DCS), a partial agonist at the glycine recognition site of the NMDA receptor in the amygdala. DCS is an established antibiotic drug for the chronic treatment of tuberculosis in humans, but has only recently been investigated as an augmentation therapy for psychological treatment procedures. The review of the literature provides preliminary support for the use of acute dosing of DCS as an adjunctive intervention to exposure therapy for anxiety disorders, including specific phobia and social anxiety disorder. Negative results have recently been reported in the treatment of subclinical fears of animals. These studies suggest that DCS needs to be administered on an acute rather than a chronic dosing schedule, include sufficient time for memory consolidation, and be administered together with psychological treatment that leaves sufficient room for further improvement. It remains to be seen whether these highly promising findings represent reliable pharmacological strategies to enhance exposure therapy of anxiety disorders. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Fl, Boston, MA 02215 USA. EM shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 FU NIMH NIH HHS [R01 MH078308, R01 MH078308-01A1] NR 69 TC 73 Z9 74 U1 3 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1080-563X J9 CNS DRUG REV JI CNS Drug Rev. PD FAL-WIN PY 2006 VL 12 IS 3-4 BP 208 EP 217 DI 10.1111/j.1527-3458.2006.00208.x PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 122KW UT WOS:000243226900003 PM 17227287 ER PT J AU Marsolek, CJ Schnyer, DM Deason, RG Ritchey, M Verfaellie, M AF Marsolek, Chad J. Schnyer, David M. Deason, Rebecca G. Ritchey, Maureen Verfaellie, Mieke TI Visual antipriming: Evidence for ongoing adjustments of superimposed visual object representations SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article ID IMPLICIT MEMORY; DISTRIBUTED-MEMORY; PERCEPTUAL SPECIFICITY; RECOGNITION MEMORY; WORD RECOGNITION; TEMPORAL CORTEX; MODEL; MECHANISMS; IDENTIFICATION; INFORMATION AB A fundamental question of memory is whether the representations of different items are stored in localist/discrete or superimposed/overlapping manners. Neural evidence suggests that neocortical areas underlying visual object identification utilize superimposed representations that undergo continual adjustments, but there has been little corroborating behavioral evidence. We hypothesize that the representation of an object is strengthened, after it is identified, via small representational changes; this strengthening is responsible for repetition priming for that object, but it should also be responsible for antipriming of other objects that have representations superimposed with that of the primed object. Functional evidence for antipriming is reported in young adults, amnesic patients, and matched control participants, and neurocomputational models. The findings from patients dismiss explicit memory explanations, and the models fit the behavioral performance exceptionally well. Putative purposes of priming and comparisons with other theories are discussed. Priming and antipriming may reflect ongoing adjustments of superimposed representations in neocortex. C1 Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. Boston VA Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Notre Dame, Notre Dame, IN 46556 USA. RP Marsolek, CJ (reprint author), Univ Minnesota, Dept Psychol, 75 E River Rd, Minneapolis, MN 55455 USA. EM chad.j.marsolek-1@umn.edu FU NICHD NIH HHS [HD07151]; NIMH NIH HHS [K23MH64004]; NINDS NIH HHS [P50NS26985] NR 62 TC 8 Z9 8 U1 1 U2 2 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2006 VL 6 IS 3 BP 163 EP 174 DI 10.3758/CABN.6.3.163 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 120LO UT WOS:000243086400001 PM 17243353 ER PT J AU Helms, JE Henze, KT Sass, TL Mifsud, VA AF Helms, Janet E. Henze, Kevin T. Sass, Terry L. Mifsud, Venus A. TI Treating Cronbach's alpha reliability coefficients as data in counseling research SO COUNSELING PSYCHOLOGIST LA English DT Article ID INTERNAL CONSISTENCY; SCORE RELIABILITY; CONFIDENCE-INTERVALS; 2 TESTS; SCALE; SAMPLE; PSYCHOMETRICS; CONSTRUCTION; METAANALYSIS; HYPOTHESIS AB Scientific associations and measurement experts in psychology and education have voiced various standards and best-practice recommendations concerning reliability data over the years. Yet in the counseling psychology literature, there is virtually no single-source compilation and articulation of good practices for reporting, analyzing, and interpreting reliability to guide applied researchers intending to use scales rather than develop them. Therefore, focusing on Cronbach's alpha internal consistency reliability estimates, this article (a) defines and provides rationales for seven broad categories of good practices for reporting, analyzing, interpreting, and using reliability data and (b) illustrates some pragmatic strategies for implementing the good practices with respect to reliability data in quantitative studies involving already-developed scales. The authors' recommendations for good rather than best practices acknowledge that additional or alternative practices may be required when scale development is the researcher's focus. The authors summarize their good practices in tabular form. C1 Boston Coll, Inst Study & Promot Race & Culture, Chestnut Hill, MA 02467 USA. Dana Farber Canc Inst, Boston, MA USA. RP Helms, JE (reprint author), Boston Coll, Inst Study & Promot Race & Culture, 318 Campion Hall, Chestnut Hill, MA 02467 USA. EM helmsja@bc.edu NR 57 TC 83 Z9 88 U1 0 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0011-0000 J9 COUNS PSYCHOL JI Couns. Psychol. PD SEP PY 2006 VL 34 IS 5 BP 630 EP 660 DI 10.1177/0011000006288308 PG 31 WC Psychology, Applied SC Psychology GA 081OW UT WOS:000240327900003 ER PT J AU Alter, G Altfeld, M AF Alter, Galit Altfeld, Marcus TI NK cell function in HIV-1 infection SO CURRENT MOLECULAR MEDICINE LA English DT Review ID NATURAL-KILLER-CELLS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; MHC CLASS-I; LINKED LYMPHOPROLIFERATIVE DISEASE; IMMUNOGLOBULIN-LIKE RECEPTORS; LARGE GRANULAR LYMPHOCYTES; IMMUNE-DEFICIENCY-SYNDROME; WISKOTT-ALDRICH-SYNDROME; BLOOD MONONUCLEAR-CELLS AB NK cells are critical effector cells of the innate immune response to malignancy and infection. These cells have a wide array of direct antiviral activities and have been critically implicated in the regulation and induction of an effective adaptive immune response. Although the pivotal role of this cell subset in the context of a number of viral infections is well established, the role of NK cells in HIV-1 infection is less well understood. Recent data has demonstrated the association between an NK cell receptor,, KIR3DS1, and it's ligand, HLA-Bw4 with an isoleucine at position 80, and slower disease progression. This data suggests that NK cells may play an essential role in the control of HIV-1 disease, and has provided the impetus to begin to better understand the role of this cell subset in the context of HIV-1 infection, replication, and pathogenesis. Here we present a review of the literature pertaining to both the effect of HIV-1 infection on NK cell activity and the potential role that this subset of cells may play in controlling HIV-1 disease. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02129 USA. EM maltfeld@partners.org NR 122 TC 33 Z9 33 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD SEP PY 2006 VL 6 IS 6 BP 621 EP 629 DI 10.2174/156652406778195035 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 073NX UT WOS:000239751000001 PM 17022732 ER PT J AU Pandol, SJ AF Pandol, Stephen J. TI Acute pancreatitis SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE enteral nutrition; necrosis; pancreatitis; trypsin; unfolded protein response ID NECROTIZING PANCREATITIS; ZYMOGEN ACTIVATION; N-ACETYLCYSTEINE; ENDOPLASMIC-RETICULUM; ACINAR-CELLS; LIVER-INJURY; SUBSTANCE-P; MICE; DECREASES; SEVERITY AB Purpose of review This review presents advances in our understanding of the pathobiologic responses of acute pancreatitis from studies using animal models of experimental pancreatitis as well as results of key clinical trials and observations. Recent findings The reports during the past year show significant advances in our understanding of the pathobiology of acute pancreatitis. In particular, there are findings presented that are relevant to our further understanding of pancreatic intracellular digestive enzyme activation; the pancreatic inflammatory response; and cell death responses such as necrosis and apoptosis. Other reports add to understanding of the control of microcirculatory disturbances in acute pancreatitis, and of the role of the pancreatic neural system in regulating the microcirculation as well as the pain associated with the disorder. Finally, there are clinical trials showing benefits of enteral feeding on outcome of acute pancreatitis as well as the finding that diclofenac prevents endoscopic retrograde cholangiopancreatography-induced pancreatitis. Summary Our understanding of the mechanistic processes that mediate the pathobiologic responses of pancreatitis is rapidly evolving. In addition, we now have initial evidence for potential treatment strategies for this disorder. Testing treatment strategies will lead to improved therapies and outcomes for patients with acute pancreatitis. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Pandol, SJ (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Bldg 258 Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Stephen.Pandol@med.va.gov NR 42 TC 28 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2006 VL 22 IS 5 BP 481 EP 486 DI 10.1097/01.mog.0000239861.89209.5f PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080XL UT WOS:000240281700002 PM 16891878 ER PT J AU Brugge, WR AF Brugge, William R. TI Endoscopic management of esophageal malignancy: lessons learned from gastric cancer SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material ID BARRETTS-ESOPHAGUS; MUCOSAL RESECTION; DYSPLASIA; NEOPLASMS; RISK C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM WBrugge@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2006 VL 22 IS 5 BP 527 EP 528 DI 10.1097/01.mog.0000239867.19705.74 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080XL UT WOS:000240281700008 PM 16891884 ER PT J AU Yusuf, TE Brugge, WR AF Yusuf, Tony E. Brugge, William R. TI Endoscopic therapy of benign pyloric stenosis and gastric outlet obstruction SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE balloon dilation; controlled radial expansion balloon; endoscopy; gastric outlet obstruction; pyloric stenosis; stricture ID PEPTIC-ULCER DISEASE; GUIDED BALLOON DILATION; TERM FOLLOW-UP; HELICOBACTER-PYLORI; PRELIMINARY EXPERIENCE; DUODENAL STENOSIS; INFECTION; DILATATION; ERADICATION; STRICTURES AB Purpose of review To examine the short and long-term success rates of balloon dilation of pyloric stenosis. Recent findings Several large studies have demonstrated high rates of success for the relief of symptoms from pyloric stenosis using through-the-scope balloons. These dilating balloons readily increase the diameter of the stenotic pylorus on average from 6 to 16 mm. Patients who require more than two dilations are at high risk of endoscopic failure and the need for surgical intervention. Rapid re-stenosis rates are observed in patients with malignant pyloric obstruction. Since many patients with benign pyloric stenosis have underlying ulcer disease, helicobacter infection is a relatively common finding. Eradication of this infection at the time of balloon dilation will ensure higher long-term success rates. Summary In summary, benign pyloric stenosis can be readily treated with. endoscopic balloon dilation and should be the first-line therapy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. EM wbrugge@partners.org NR 26 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2006 VL 22 IS 5 BP 570 EP 573 DI 10.1097/01.mog.0000239874.13867.41 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080XL UT WOS:000240281700015 PM 16891891 ER PT J AU James, JA Harley, JB Scofield, RH AF James, Judith A. Harley, John B. Scofield, R. Hal TI Epstein-Barr virus and systemic lupus erythematosus SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE environmental factors; Epstein-Barr virus; etiology; systemic lupus erythematosus ID ANTI-SM ANTIBODIES; NUCLEAR ANTIGEN-1; HEMOPHAGOCYTIC SYNDROME; COMPLEMENT RECEPTOR-2; RHEUMATOID-ARTHRITIS; PEPTIDE IMMUNIZATION; HUMORAL AUTOIMMUNITY; ADULT PATIENTS; EPITOPE; INFECTION AB Purpose of review Systemic lupus erythematosus is a complex human disease likely influenced by a compilation of necessary, but not individually sufficient, features. Although many genetic and environmental factors are associated, this review will focus on the evolving evidence for key Epstein-Barr virus specific roles. Recent findings Recent studies have shown additional molecular mimicry mechanisms between early events in lupus autoimmunity and specific Epstein-Barr virus responses. in addition, several recent papers have demonstrated increased Epstein-Barr viral load, increased numbers of latently infected peripheral B cells, impaired functional T cell responses, and association of the presence of Epstein-Barr virus DNA in systemic lupus erythematosus patients compared with controls. Additional work has continued to show association of various aspects of Epstein-Barr virus serology with systemic lupus erythematosus and a recent paper outlines differences in the pediatric systemic lupus erythematosus humoral immune response to Epstein-Barr virus nuclear antigen-1 compared with matched controls. Summary This review will briefly outline the recent advances that show serologic, DNA, gene expression, viral load, T cell responses, humoral fine specificity, and molecular mimicry evidence for differences between systemic lupus erythematosus patients and controls and the impact that these findings have on understanding the role of Epstein-Barr virus in systemic lupus. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM jamesj@omrf.ouhsc.edu FU NCRR NIH HHS [RR 020143, RR 15577]; NIAID NIH HHS [AI 031584, AI 053747, AI 062629]; NIAMS NIH HHS [AR 48045, AR 053734, AR 14467, AR 45451, AR 48204, AR 48940, AR 49084] NR 55 TC 56 Z9 57 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD SEP PY 2006 VL 18 IS 5 BP 462 EP 467 DI 10.1097/01.bor.0000240355.37927.94 PG 6 WC Rheumatology SC Rheumatology GA 086DI UT WOS:000240652900004 PM 16896283 ER PT J AU Dall'Era, M Wofsy, D AF Dall'Era, Maria Wofsy, David TI Clinical trial design in systemic lupus erythematosus SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE clinical trial design; systemic lupus erythematosus; therapeutic agents ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RECOMMENDATIONS; QUALITY AB Purpose of review The purpose of this review is to discuss the challenges inherent in the design of clinical trials for patients with systemic lupus erythematosus. Recent findings Recent years have witnessed a renewed interest in the conduct of systemic lupus erythematosus clinical trials. Three key design decisions play particularly critical roles in determining the fate of these trials: selection of the study, population from among patients with very heterogeneous disease manifestations; selection of the treatment and control regimens; and selection of the primary endpoint. Four recent randomized, controlled trials dealt with these decisions in the context of a variety of interventions, including new biologic agents, hormonal therapies, and anti-metabolites. These trials are informative about the implications of each approach. Summary Systemic lupus erythematosus investigators are faced with substantial trial design challenges because of the inherently complex nature of this disease. The hope is that lessons learned from prior and ongoing trials will inform future trial design such that the efficacy of new agents can be determined and new therapies will become available for patients with SLE. C1 Univ Calif San Francisco, Div Rheumatol, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Wofsy, D (reprint author), Univ Calif San Francisco, Div Rheumatol, San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM wofsyd@medsch.ucsf.edu NR 7 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD SEP PY 2006 VL 18 IS 5 BP 476 EP 480 DI 10.1097/01.bor.0000240357.22680.63 PG 5 WC Rheumatology SC Rheumatology GA 086DI UT WOS:000240652900006 PM 16896285 ER PT J AU Baxter, FO Came, PJ Abell, K Kedjouar, B Huth, M Rajewsky, K Pasparakis, M Watson, CJ AF Baxter, Fiona O. Came, Paul J. Abell, Kathrine Kedjouar, Blandine Huth, Marion Rajewsky, Klaus Pasparakis, Manolis Watson, Christine J. TI IKK beta/2 induces TWEAK and apoptosis in mammary epithelial cells SO DEVELOPMENT LA English DT Article ID NF-KAPPA-B; FORKHEAD TRANSCRIPTION FACTOR; NECROSIS-FACTOR-ALPHA; GLAND INVOLUTION; FAS LIGAND; CANCER-THERAPY; TNF-ALPHA; ACTIVATION; EXPRESSION; PROMOTER AB The Nuclear Factor-kappa B (NF-kappa B) family of transcription factors are ubiquitously expressed and control a wide range of cellular responses, including apoptosis, proliferation, differentiation, inflammation and immunity. Here, we investigated the function of the NF-kappa B upstream regulator I kappa B kinase 2/beta (IKK2) in apoptosis regulation in the normal physiological setting of regressing mammary gland. Conditional deletion of the gene encoding IKK2 resulted, surprisingly, in delayed apoptosis and remodelling, and abrogation of caspase 3 cleavage. This failure to induce involution was associated with reduced expression, within 24 hours of involution, of the death receptor (DR) ligand TNF and its receptor TNFR1, which are known NF-kappa B targets. This was associated with elevated levels of active AKT and phosphorylated FOXO3a. Furthermore, we show that expression of TWEAK, another DR ligand, is dramatically downregulated, even in heterozygous IKK2 mammary glands. Unlike other DR ligands, the TWEAK promoter has six consensus FOXO-binding sites, further suggesting that it is differentially regulated. Interestingly, a cleaved form of TWEAK is upregulated during involution. This unexpected function of the IKK2/NF-kappa B pathway as a regulator of TWEAK expression and inducer of apoptosis has significant consequences for future therapeutic approaches for cancer and inflammatory diseases. C1 Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. EMBL Mouse Lab Program, I-00016 Monterotondo, Rome, Italy. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Watson, CJ (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM cjw53@mole.bio.cam.ac.uk RI watson, Christine/B-1431-2012 NR 40 TC 52 Z9 54 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 1 PY 2006 VL 133 IS 17 BP 3485 EP 3494 DI 10.1242/dev.02502 PG 10 WC Developmental Biology SC Developmental Biology GA 073QW UT WOS:000239758700021 PM 16887827 ER PT J AU Arango, NA Huang, TT Fujino, A Pieretti-Vanmarcke, R Donahoe, PK AF Arango, Nelson A. Huang, Tiffany T. Fujino, Akihiro Pieretti-Vanmarcke, Rafael Donahoe, Patricia K. TI Expression analysis and evolutionary conservation of the mouse germ cell-specific D6Mm5e gene SO DEVELOPMENTAL DYNAMICS LA English DT Article DE sexual differentiation; ovary development; gametogenesis; meiosis ID DIFFERENTIATION; MEIOSIS; CYSTS; OVARY AB During our search for genes required for gonadal development and function in the mouse, we identified D6Mm5e (DNA segment, Chr 6. Miriam Meisler 5, expressed), a gene with an expression pattern highly restricted to the embryonic ovary and the postnatal testis. Based on RT-PCR, Northern blot, and in situ hybridization analyses, we show that D6Mm5e is expressed in the germ cells of the female embryo upon their initial entry into meiosis, and in male germ cells during the last stages of spermatogenesis. Two transcripts are detected in the gonads resulting from the alternative splicing of exon 8. This splicing event does not introduce a frame shift, and creates an mRNA product that uses the same stop codon as the longer transcript. Although D6Mm5e does not belong to any known protein family and does not contain any known protein signature motifs, the high level of evolutionary conservation and the cellular and temporal expression suggest that D6Mm5e may have a role in male and female gametogenesis. Here we report the gonad-restricted mRNA expression profile of D6Mm5e in the mouse, and the evolutionary conservation of its amino acid sequence. Developmental Dynamics 235:2613-2619, 2006. (c) 2006 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Arango, NA (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, 185 Cambridge St,MCPZN6212, Boston, MA 02114 USA. EM arango@helix.mgh.harvard.edu FU NICHD NIH HHS [F32 HD43539, HD32112] NR 15 TC 6 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2006 VL 235 IS 9 BP 2613 EP 2619 DI 10.1002/dvdy.20907 PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 080QG UT WOS:000240262000029 PM 16881047 ER PT J AU Evgenov, NV Medarova, Z Pratt, J Pantazopoulos, P Leyting, S Bonner-Weir, S Moore, A AF Evgenov, Natalia V. Medarova, Zdravka Pratt, John Pantazopoulos, Pamela Leyting, Simone Bonner-Weir, Susan Moore, Anna TI In vivo imaging of immune rejection in transplanted pancreatic islets SO DIABETES LA English DT Article ID MAGNETIC-RESONANCE TRACKING; IRON-OXIDE; XENOGENEIC ISLETS; CELLS; LIVER; LANGERHANS; MODEL; TERM; NANOPARTICLES; XENOGRAFTS AB As islet transplantation becomes an acceptable clinical modality for restoring normoglycemia in type I diabetic patients, there is a crucial need for noninvasive assessment of the fate of the grafts. In spite of the success of the Edmonton Protocol, a significant graft loss occurs due to immunological and nonimmunological events immediately after transplantation. Allogeneic rejection in graft recipients is one of the major reasons for islet death and graft failure. Therefore, monitoring the islet rejection using reliable noninvasive methods would significantly aid in clinical assessment of graft success. We have previously developed a method to detect transplanted islets noninvasively using magnetic resonance imaging (MRI). For this procedure, human pancreatic islets are labeled with an MRI contrast agent that enables their visualization on magnetic resonance images. In our present study, we not only detected labeled human islets in a preclinical intrahepatic model of human islet transplantation in mice but also showed that islet rejection can be monitored noninvasively and repeatedly in real time by MRI. In addition, in this study, we have adapted, for islet cell labeling, a Food and Drug Administration-approved commercially available contrast agent, Feridex, that is used clinically for liver imaging. We believe that this agent, in combination with our preclinical model of islet transplantation, will facilitate the transition of imaging immune rejection to clinical trials. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab,MGH,MIT,HMS, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab,MGH,MIT,HMS, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU NIDDK NIH HHS [DK071225, DK072137] NR 39 TC 103 Z9 106 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2006 VL 55 IS 9 BP 2419 EP 2428 DI 10.2337/db06-0484 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LC UT WOS:000240456400003 PM 16936189 ER PT J AU Bochenski, J Placha, G Wanic, K Malecki, M Sieradzki, J Warram, JH Krolewski, AS AF Bochenski, Jacek Placha, Grzegorz Wanic, Krzysztof Malecki, Maciej Sieradzki, Jacek Warram, James H. Krolewski, Andrzej S. TI New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; K121Q POLYMORPHISM; POLISH POPULATION; GENE; SUSCEPTIBILITY; HAPLOTYPES; MELLITUS; GLUCOSE; VARIANT; ALLELE AB The K121Q polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is associated with type 2 diabetes and obesity. The possibility of other ENPP1 polymorphisms influencing these phenotypes has received little attention. Our aim was to examine the associations of tagging single nucleotide polymorphisms (SNPs) and haplotypes of the linkage disequilibrium (LD) block containing K121Q polymorphism with type 2 diabetes in a Polish population, controlling for any effect of obesity. We genotyped. 426 type 2 diabetic case and 370 control subjects for seven SNPs in ENPP1. In the total group, neither type 2 diabetes nor obesity was significantly associated with any SNP. However, in obese subjects, two SNIs were significantly associated with type 2 diabetes: the Q allele of K121Q (odds ratio 1.6 [95% Cl 1.003-2.6]) and T allele of rs997509 (4.7 [1.6-13.9]). In the LD block, four SNPs plus the K121Q polymorphism distinguished six haplotypes, three of which carried the Q allele. Interestingly, the T allele of rs997509 sufficed to distinguish a 121Q-carrying haplotype that was significantly more associated with type 2 diabetes than the other two (4.2 [1.3-13.5]). These other two 121Q-carrying haplotypes were not associated with type 2 diabetes. In conclusion, we found a new SNP, rs997509, in intron 1 that is strongly associated with risk of type 2 diabetes in obese individuals. The molecular mechanisms underlying this association are unknown. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Jagiellonian Univ, Sch Med, Dept Metab Dis, Krakow, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU FIC NIH HHS [TW01351]; NIDDK NIH HHS [DK47475] NR 22 TC 50 Z9 51 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2006 VL 55 IS 9 BP 2626 EP 2630 DI 10.2337/db06-0191 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LC UT WOS:000240456400027 PM 16936213 ER PT J AU Zhang, CL Qi, L Hunter, DJ Meigs, JB Manson, JE van Dam, RM Hu, FB AF Zhang, Cuilin Qi, Lu Hunter, David J. Meigs, James B. Manson, JoAnn E. van Dam, Rob M. Hu, Frank B. TI Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of US women and men SO DIABETES LA English DT Article ID BETA-CATENIN; MELLITUS; WNT; CLASSIFICATION; EXPRESSION; DIAGNOSIS; DISEASE; CANCER; ONSET AB Emerging evidence indicates that variation in the transcription factor 7-like 2 (TCF7L2) gene may play a role in the pathogenesis of type 2 diabetes. In a prospective, nested, case-control study (n = 3,520) within the Nurses' Health Study (687 type 2 diabetic case and 1,051 control subjects) and the Health Professionals Follow-up Study (886 case and 896 control subjects), we examined the association of a common variant of the TCF7L2 gene (rs1255372 [T/G]) with type 2 diabetes risk among Caucasians. Frequencies of the T-allele were significantly higher among case than control subjects; each copy of the T-allele was associated with a 1.32-fold (P = 0.0002) and 1.53-fold (P < 0.0001) increased type 2 diabetes risk in women and men, respectively. The odds ratios (95% CI) associated with homozygous carriers of the T-allele were 1.86 (1.30-2.67) and 2.15 (1.48-3.13) in women and men, respectively. Population-attributable risks for diabetes associated with the T-allele were 14.8 and 22.3% for women and men, respectively. In a meta-analysis of 3,347 case and 3,947 control sujects, each copy of the T-allele was associated with a 1.48-fold increased risk (P < 10(-16)). Our findings confirm that the TCF7L2 gene represents an important locus for predicting inherited susceptibility to type 2 diabetes. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Zhang, CL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM cuilin.zhang@channing.harvard.edu; frank.hu@channing.harvard.edu RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845] NR 24 TC 141 Z9 148 U1 0 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2006 VL 55 IS 9 BP 2645 EP 2648 DI 10.2337/db06-0643 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LC UT WOS:000240456400030 PM 16936216 ER PT J AU Ng, DPK Placha, G Choo, S Chia, KS Warram, JH Krolewski, AS AF Ng, Daniel P. K. Placha, Grzegorz Choo, Serena Chia, Kee-seng Warram, James H. Krolewski, Andrzej S. TI A disease haplotype for advanced nephropathy in type 2 diabetes at the ACE locus SO DIABETES LA English DT Article ID CONVERTING-ENZYME GENE; INSERTION DELETION POLYMORPHISM; ANGIOTENSIN-II; HYPERTENSION; ASSOCIATION; RECEPTOR; KIDNEY; CELLS; DCP1 AB Previous investigations of the ACE gene is a susceptibility factor for diabetic nephropathy have primarily focused on its insertion/deletion (Ins/Del) polymorphism. In a departure from these earlier studies, we used three tagging markers (A-5466C, T-3892C, and Ins/Del) at the ACE locus to test for disease haplotype associations. A case-control study design was used where case subjects were type 2 diabetic patients with advanced diabetic nephropathy, as indicated by the presence of proteinuria or chronic renal failure/end-stage renal disease, while control subjects were normoalbuminuric, despite > 6 years of diabetes. None of the individual markers showed significant disease association when considered on their own. However, haplotype analyses revealed a near doubling in the prevalence of the A.T.D risk haplotype in case subjects (0.136) compared with control subjects (0.075) (P = 0.009), thus providing first evidence for a disease haplotype for advanced diabetic nephropathy at the ACE locus. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117548, Singapore. Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Warsaw Med Univ, Dept Hypertens, Warsaw, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu RI CHIA, Kee Seng/C-5790-2011 FU NIDDK NIH HHS [DK053534, DK058549] NR 17 TC 23 Z9 24 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2006 VL 55 IS 9 BP 2660 EP 2663 DI 10.2337/db06-0496 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LC UT WOS:000240456400033 PM 16936219 ER PT J AU Carr, DB Heckbert, SR Utzschneher, KM Boyko, EJ Hull, RL Fujimoto, WY Tong, J Kahn, SE Wallace, TM Kodama, K Shofer, JB AF Carr, Darcy B. Heckbert, Susan R. Utzschneher, Kristina M. Boyko, Edward J. Hull, Rebecca L. Fujimoto, Wilfred Y. Tong, Jenny Kahn, Steven E. Wallace, Tara M. Kodama, Keiichi Shofer, Jane B. CA Amer Diabet Assoc GENNID Study Grp TI Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; LIFE-STYLE; MORTALITY; PREVENTION; PREVALENCE; METABOLISM; ADULTS; VASODILATATION AB OBJECTIVE - We sought to determine whether a history of gestational diabetes mellitus (GDM) further increases the risk of cardiovascular disease (CVD) in parous women with first-degree relatives with type 2 diabetes. RESEARCH DESIGN AND METHODS - Women with (n = 332) and without (n = 663) a history of GDM were compared regarding 1) the revised National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria, 2) the prevalence of type 2 diabetes, and 3) self-reported CVD. RESULTS -' Women with prior GDM were younger (48.6 +/- 0.7 vs. 52.4 +/- 0.6 years [means - SE]; P < 0.001) and less likely to be postmenopausal (48.3 vs. 57.9%; P < 0.005). Although both groups were obese (BMI 34.4 +/- 1.2 vs. 33.7 +/- 0.6 kg/m(2)), women with prior GDM were more likely to have metabolic syndrome (86.6 vs. 73.5%; P < 0.001) and type 2 diabetes (93.4% vs. 63.3%; P < 0.001). Moreover, they had a higher prevalence of CVD (15.5 vs. 12.4%; adjusted odds ratio 1.85 [95% CI 1.21-2.82]; P = 0.005) that occurred at a younger age (45.5 +/- 2.2 vs. 52.5 +/- 1.9 years; P = 0.02) and was independent of metabolic syndrome (1.74 [1.10-2.76]; P = 0.02) and type 2 diabetes (1.56 [1.002-2.43]; P < 0.05). CONCLUSIONS - Among women with a family history of type 2 diabetes, those with prior GDM were even more likely to not only have CVD risk factors, including metabolic syndrome and type 2 diabetes, but also to have experienced CVD events, which occurred at a younger age. Thus, women with both a family history of type 2 diabetes and personal history of GDM may be especially suitable for early interventions aimed at preventing or reducing their risk of CVD and diabetes. C1 Univ Washington, Dept Obstet & Gynecol, Div Maternal Fetal Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. Univ Washington, Dept Rehabil Res & Dev, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Cardiovasc Res Unit, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Carr, DB (reprint author), Univ Washington, Dept Obstet & Gynecol, Div Maternal Fetal Med, Box 356460, Seattle, WA 98195 USA. EM darcarr@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NCRR NIH HHS [RR 16066]; NIDDK NIH HHS [DK 02654, DK 17047] NR 36 TC 107 Z9 111 U1 0 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2006 VL 29 IS 9 BP 2078 EP 2083 DI 10.2337/dc05-2482 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LG UT WOS:000240456800014 PM 16936156 ER PT J AU Hamman, RF Wing, RR Edelstein, SL Lachin, JM Bray, GA Delahanty, L Hoskin, M Kriska, AM Mayer-Davis, EJ Pi-Sunyer, X Regensteiner, J Venditti, B Wylie-Rosett, J AF Hamman, Richard F. Wing, Rena R. Edelstein, Sharon L. Lachin, John M. Bray, George A. Delahanty, Linda Hoskin, Mary Kriska, Andrea M. Mayer-Davis, Elizabeth J. Pi-Sunyer, Xavier Regensteiner, Judith Venditti, Beth Wylie-Rosett, Judith CA Diabet Prevention Program Res Grp TI Effect of weight loss with lifestyle intervention on risk of diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; PREVENTION-PROGRAM; FAT DISTRIBUTION; BASE-LINE; MELLITUS; EXERCISE; OBESITY; DIET; OVERWEIGHT; REDUCTION AB OBJECTIVE - Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants. RESEARCH DESIGN AND METHODS - For this Study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up. RESULTS - A total of 1,079 participants were aged 25-84 years (mean 50.6 years, BMI 33.9 kg/m(2)). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.5]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of Calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence. CONCLUSIONS - interventions to reduce diabetes risk should primarily target weight reduction. C1 George Washington Univ, Diabet Prevent Program Coodinat Ctr, Ctr Biostat, Rockville, MD 20852 USA. Univ Colorado, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Massachusetts Gen Hosp, Ctr Diabet Res, Boston, MA USA. NIDDK, SW Indian Ctr, Phoenix, AZ USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ S Carolina, Sch Publ Hlth, Columbia, SC 29208 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Hamman, RF (reprint author), George Washington Univ, Diabet Prevent Program Coodinat Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu OI Kriska, Andrea/0000-0002-3522-0869; Lachin, John/0000-0001-9838-2841 FU NIDDK NIH HHS [U01 DK048489] NR 29 TC 392 Z9 401 U1 1 U2 31 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2006 VL 29 IS 9 BP 2102 EP 2107 DI 10.2337/dc06-0560 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LG UT WOS:000240456800018 PM 16936160 ER PT J AU Ginde, AA Pelletier, AJ Camargo, CA AF Ginde, Adit A. Pelletier, Andrea J. Camargo, Carlos A., Jr. TI National study of US emergency department visits with diabetic ketoacidosis, 1993-2003 SO DIABETES CARE LA English DT Article ID INTENSIVE-CARE-UNIT C1 Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Ginde, AA (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, 1 Deaconess Rd,WCC-2, Boston, MA 02215 USA. EM aginde@bidmc.harvard.edu RI Siry, Bonnie/D-7189-2017 NR 10 TC 11 Z9 11 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2006 VL 29 IS 9 BP 2117 EP 2119 DI 10.2337/dc06-0627 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LG UT WOS:000240456800021 PM 16936163 ER PT J AU Parikh, H Carlsson, E Chutkow, WA Johansson, L Saxena, R Krook, A Bjornholm, M Zierath, J Ridderstrale, M Altshuler, D Lee, RT Vaag, A Groop, LC Mootha, VK AF Parikh, H. Carlsson, E. Chutkow, W. A. Johansson, L. Saxena, R. Krook, A. Bjornholm, M. Zierath, J. Ridderstrale, M. Altshuler, D. Lee, R. T. Vaag, A. Groop, L. C. Mootha, V. K. TI Identification of TXNIP as a marker and regulator of glucose homeostasis in humans SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Lund Univ, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. Brigham & Womens Hosp, Div Cardiovasc, Cambridge, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Karolinska Inst, Dept Physiol & Pharmacol, Sect Integrat Physiol, Stockholm, Sweden. Karolinska Inst, Dept Mol Med & Surg Sci, Sect Integrat Physiol, Stockholm, Sweden. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RI Altshuler, David/A-4476-2009; Krook, Anna/K-1192-2015 OI Altshuler, David/0000-0002-7250-4107; Krook, Anna/0000-0002-0891-0258 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0031 BP 21 EP 21 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200032 ER PT J AU Klint, C Kulkarni, RN Holm, C Winzell, MS AF Klint, C. Kulkarni, R. N. Holm, C. Winzell, M. Sorhede TI Transgenic overexpression of hormone-sensitive lipase in immortalised mouse beta-cells rescues the cells from lipotoxicity SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Lund Univ, Dept Expt Med Sci, S-22100 Lund, Sweden. Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Lund Univ, Dept Clin Sci, S-22100 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0099 BP 63 EP 63 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200099 ER PT J AU Behar, A Cohen-Boulakia, F Tarhzaoui, K Leger, G Lestrade, R Valensi, P AF Behar, A. Cohen-Boulakia, F. Tarhzaoui, K. Leger, G. Lestrade, R. Valensi, P. TI Rosiglitazone reverses the alterations of capillary permeability but does not improve nerve function in Zucker Diabetic Fatty rats SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. Joslin Diabet Ctr, Boston, MA USA. Rigshosp, DK-2100 Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0131 BP 84 EP 84 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200131 ER PT J AU Major-Pedersen, A Ihlemann, N Kveiborg, B Christiansen, B Hermann, TS Dominguez, H Nielsen, DB Madsen, CR Svendsen, OL Kober, L Torp-Pedersen, C AF Major-Pedersen, A. Ihlemann, N. Kveiborg, B. Christiansen, B. Hermann, T. S. Dominguez, H. Nielsen, D. B. Madsen, C. R. Svendsen, O. L. Kober, L. Torp-Pedersen, C. TI Insulin resistance and postprandial endothelial dysfunction: Does attenuation of postprandial hyperglycaemia make a difference? SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. Joslin Diabet Ctr, Boston, MA 02115 USA. Rigshosp, DK-2100 Copenhagen, Denmark. RI Torp-Pedersen, Christian/E-5931-2013; OI DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0132 BP 84 EP 85 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200132 ER PT J AU Dodson, PM Aiello, LP Vignati, L Sheetz, MJ Zhi, X Girach, A Davis, MD Milton, RC AF Dodson, P. M. Aiello, L. P. Vignati, L. Sheetz, M. J. Zhi, X. Girach, A. Davis, M. D. Milton, R. C. TI Effect of ruboxistaurin on diabetic macular edema and visual loss: integrated analysis of the PKC-DRS and PKC-DRS2 SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Birmingham Heartlands Hosp, Ctr Diabet, Birmingham B9 5ST, W Midlands, England. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Ophthalmol, Boston, MA 02115 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Eli Lilly & Co, Windlesham, Surrey, England. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. EMMES Corp, ARDES Coordinating Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0249 BP 157 EP 158 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200249 ER PT J AU Menzaghi, C Coco, A Salvemini, L Thompson, R De Cosmo, S Doria, A Trischitta, V AF Menzaghi, C. Coco, A. Salvemini, L. Thompson, R. De Cosmo, S. Doria, A. Trischitta, V. TI Heritability of serum resistin and its genetic correlation with insulin resistance-related features in non-diabetic Caucasians SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 IRCCS, Res Unit Diabetol & Endocrinol, San Giovanni Rotondo, Italy. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. Univ Roma La Sapienza, Dept Clin Sci, I-00185 Rome, Italy. RI De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016 OI De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0360 BP 223 EP 223 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200358 ER PT J AU de Koning, EJP Nienaber, C Yatoh, S Patterson, D Rask-Madsen, C van Zonneveld, AJ Rabelink, AJ Sharma, A Bonner-Weir, S AF de Koning, E. J. P. Nienaber, C. Yatoh, S. Patterson, D. Rask-Madsen, C. van Zonneveld, A. -J. Rabelink, A. J. Sharma, A. Bonner-Weir, S. TI Endothelial cell involvement in proliferation and differentiation of human pancreatic duct cells SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Joslin Diabet Ctr, Dept Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands. Joslin Diabet Ctr, Dept Vasc Cell Biol, Boston, MA 02215 USA. RI Rabelink, Ton/A-5316-2008 OI Rabelink, Ton/0000-0001-6780-5186 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0475 BP 290 EP 290 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200472 ER PT J AU Jermendy, A Toschi, E Koh, A Aye, T Sharma, A Weir, GC Sgroi, DC Leykin, I Bonner-Weir, S AF Jermendy, A. Toschi, E. Koh, A. Aye, T. Sharma, A. Weir, G. C. Sgroi, D. C. Leykin, I. Bonner-Weir, S. TI Generalised immaturity of metabolic pathways in neonatal beta cells SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Islet Transplantat & Cell Biol, Joslin Diabet Ctr, Boston, MA USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0479 BP 292 EP 293 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626200476 ER PT J AU Maurovich-Horvat, P Massaro, J Fox, CS Moselewski, F O'Donnell, CJ Hoffmann, U AF Maurovich-Horvat, P. Massaro, J. Fox, C. S. Moselewski, F. O'Donnell, C. J. Hoffmann, U. TI Assessment of abdominal subcutaneous and visceral adipose tissue volumes with multi detector-row computed tomography SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Semmelweis Univ, Dept Cardiovasc Surg, H-1085 Budapest, Hungary. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 0764 BP 463 EP 463 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626201150 ER PT J AU Vignati, L Sheetz, MJ Girach, A Zhi, X Davis, MD Milton, RC Aiello, LP AF Vignati, L. Sheetz, M. J. Girach, A. Zhi, X. Davis, M. D. Milton, R. C. Aiello, L. P. TI Effect of the oral protein kinase C beta inhibitor rubox-istaurin on visual acuity in the PKC-DRS2 study SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. EMMES Corp, Diabet Res, Rockville, MD USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 1076 BP 656 EP 657 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626201460 ER PT J AU King, GL McGill, JB Hyslop, D Berg, PH Price, KL Kles, KA Bastyr, EJ Vignati, L AF King, G. L. McGill, J. B. Hyslop, D. Berg, P. H. Price, K. L. Kles, K. A. Bastyr, E. J. Vignati, L. TI Clinical safety of the selective PKC beta inhibitor, rubox-istaurin, in patients with diabetic microvascular complications SO DIABETOLOGIA LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 14-17, 2006 CL Copenhagen, DENMARK SP European Assoc Study Diabet C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Washington Univ, Dept Med, Sch Med, St Louis, MO 63130 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2006 VL 49 SU 1 MA 1077 BP 657 EP 657 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 085TB UT WOS:000240626201461 ER PT J AU Forooghian, F Sproule, M Westall, C Gordon, L Jirawuthiworavong, G Shimazaki, K O'Connor, P AF Forooghian, Farzin Sproule, Melanie Westall, Carol Gordon, Lynn Jirawuthiworavong, Guy Shimazaki, Kaori O'Connor, Paul TI Electroretinographic abnormalities in multiple sclerosis: possible role for retinal autoantibodies SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article DE multiple sclerosis; retina autoantibodies; electroretinogram ID CANCER-ASSOCIATED RETINOPATHY; EXPERIMENTAL AUTOIMMUNE PANENCEPHALITIS; CYSTOID MACULAR EDEMA; RETINITIS-PIGMENTOSA; VITREOUS FLUOROPHOTOMETRY; FLASH ELECTRORETINOGRAM; DISEASE-ACTIVITY; LEWIS RAT; ANTIBODIES; BREAKDOWN AB Background Multiple sclerosis (MS) has been associated with inflammation of the uveal tract, suggesting an immunological link between the uvea and central nervous system (CNS) in this disease. The retina is embryologically derived from the CNS, and it is conceivable that retinal antigens may also be recognized by the immune system in MS. Electroretinographic abnormalities, as well as retinal autoantibodies, have previously been described in MS. We performed this study to further explore the possibility of retinal autoimmunity in MS. Methods Thirty-four patients with clinically definite MS and thirty-seven healthy controls were recruited. All patients and controls had standard electroretinographic (ERG) testing done, as well as a brightflash ERG protocol to isolate rod photoreceptor function. Patient and control sera were analyzed for the presence of antiretinal antibodies using Western blot techniques. Results We found statistically significant differences between MS patients and controls in four ERG parameters. In the MS group, implicit times of the rod-cone b-wave response, cone b-wave response, and rod photoreceptor response were increased. The amplitudes of the photopic oscillatory potentials were reduced in the MS group. Patients with the highest titres of retinal autoantibodies had delayed rod-cone b-wave implicit times and diminished photopic oscillatory potential amplitudes. Conclusions We report ERG evidence of retinal dysfunction in patients with MS. We also report the first use of the brightflash ERG protocol in MS, which demonstrated rod photoreceptor dysfunction. Patients with the highest antiretinal antibody titres had abnormal ERG recordings. Retinal autoimmunity is a possible explanation for these observed ERG abnormalities in MS patients. C1 Hosp Sick Children, Dept Ophthalmol, Toronto, ON M5G 1X8, Canada. Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Toronto, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada. Univ Toronto, Dept Neurol, Toronto, ON, Canada. RP Forooghian, F (reprint author), Hosp Sick Children, Dept Ophthalmol, Room 10128 Elm Wing,555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM farzin.forooghian@utoronto.ca NR 37 TC 19 Z9 20 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PD SEP PY 2006 VL 113 IS 2 BP 123 EP 132 DI 10.1007/s10633-006-9022-0 PG 10 WC Ophthalmology SC Ophthalmology GA 115GD UT WOS:000242721900006 PM 16972082 ER PT J AU Goss, P AF Goss, Paul TI Breaking the 5-year barrier: Results from the MA.17 extended adjuvant trial in women who have completed adjuvant tamoxifen treatment SO EJC SUPPLEMENTS LA English DT Article; Proceedings Paper CT Satellite Symposium on the Quiet Revolution in Breast Cancer Treatment CY OCT, 2005 CL Paris, FRANCE DE hormone-receptor-positive breast cancer; extended adjuvant therapy; letrozole; placebo; tamoxifen; postmenopausal women; recurrence; disease-free survival; aromatase inhibitor ID ADVANCED BREAST-CANCER; NEOADJUVANT ENDOCRINE THERAPY; BLIND RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; PHASE-III; AROMATASE INHIBITOR; MEGESTROL-ACETATE; 1ST-LINE THERAPY; UPDATED FINDINGS; LETROZOLE AB The selective estrogen-receptor modulator, tamoxifen, has been the mainstay of adjuvant endocrine therapy for several decades, significantly improving outcomes for numerous women with hormone-receptor-positive (HR+) early breast cancer. However, tamoxifen is associated with acquired resistance: efficacy appears to decrease gradually with prolonged use, whereas the incidence of troublesome adverse events, such as thromboembolic disease and endometrial cancer, persists. Hence, long-term exposure to tamoxifen is associated with an unfavorable risk:benefit profile, limiting adjuvant tamoxifen therapy to 5 years. The majority of breast cancer recurrences and deaths occur more than 5 years after surgery, demonstrating the need for new treatment strategies for women who have completed tamoxifen therapy. Furthermore, the risk of late relapse is particularly high among women with HR+ disease, who are thus ideal candidates for further endocrine therapy. In 2003, the first interim analysis of the MA.17 trial was published, identifying letrozole as the first agent to significantly reduce the risk of recurrence in women who had completed standard adjuvant tamoxifen therapy. Over 5000 women with HR+ breast cancer were randomized to receive either letrozole or placebo within 3 months of stopping tamoxifen therapy. The trial was unblinded at the first planned interim analysis because of a highly significant (p = 0.00008) 43% reduction in the relative risk of recurrence at a median follow-up of 28.8 months. The final analysis (median follow-up 30 months) confirmed these findings, with letrozole reducing the relative risk of recurrence by 42%, equating to an absolute reduction in the risk of relapse of 4.6% at 4 years. The beneficial effect of letrozole was seen regardless of nodal status, previous chemotherapy or duration of tamoxifen treatment (> 5 years or <= 5 years), and increased with duration of therapy. Letrozole also reduced the risk of distant recurrence, and significantly improved overall survival in patients with node-positive, but not node-negative disease, becoming the first aromatase inhibitor to improve survival compared with standard treatment in early-stage breast cancer. Letrozole therapy was well tolerated: no significant detrimental effects were seen on the cardiovascular system (5.8% vs 5.6% p = 0.76), lipid metabolism (16% vs 16% p = 0.79) or global quality of life scores compared with placebo. Musculoskeletal side effects, including patient-reported new osteoporosis, were more common in patients taking letrozole. Patient-reported new osteoporosis was not associated with an increased fracture risk. Letrozole is the first agent shown to reduce the risk of late relapse after completion of tamoxifen therapy, in what is now known as the extended adjuvant setting. Letrozole is, therefore, a highly effective and well-tolerated endocrine therapy that significantly improves outcomes for women with HR+ early breast cancer. Letrozole has improved treatment options for women with early breast cancer, extending the duration of adjuvant therapy to at least 10 years. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Breast Canc, Boston, MA 02114 USA. RP Goss, P (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Breast Canc, 55 Fruit St,Cox Bldg,Suite 640, Boston, MA 02114 USA. EM pgoss@partners.org NR 29 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2006 VL 4 IS 9 BP 10 EP 15 DI 10.1016/j.ejcsup.2006.04.137 PG 6 WC Oncology SC Oncology GA 103ZU UT WOS:000241926500003 ER PT J AU Kogai, T Taki, K Brent, GA AF Kogai, T. Taki, K. Brent, G. A. TI Enhancement of sodium/iodide symporter expression in thyroid and breast cancer SO ENDOCRINE-RELATED CANCER LA English DT Review ID SODIUM-IODIDE SYMPORTER; CARCINOMA CELL-LINES; PROTEIN-KINASE-A; TISSUE-SPECIFIC EXPRESSION; HUMAN CHORIONIC-GONADOTROPIN; 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE; HISTONE DEACETYLASE INHIBITOR; EXPERIMENTAL I-131 THERAPY; HUMAN NA+/I-SYMPORTER; RETINOID-X-RECEPTORS AB The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and lactating breast. NIS mRNA and protein expression are detected in most thyroid cancer specimens, although functional iodide uptake is usually reduced resulting in the characteristic finding of a 'cold' or non-functioning lesion on a radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH) stimulation, however, is sufficient in most differentiated thyroid cancer to utilize beta-emitting radioactive iodide for the treatment of residual and metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in athyreotic patients or after recombinant human thyrotropin administration, directly stimulates NIS gene expression and/or NIS trafficking to the plasma membrane, increasing radioiodide uptake. Approximately 10-20% differentiated thyroid cancers, however, do not express the NIS gene despite TSH stimulation. These tumors are generally associated with a poor prognosis. Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression is detected in about 80% breast cancer specimens, but the fraction with functional iodide transport is relatively low. Lactogenic hormones and various, nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in vitro, but TSH has no effect. A wide range of 'differentiation' agents have been utilized to stimulate NIS expression in thyroid and breast cancer using in vitro and in vivo models, and a few have been used in clinical studies. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. There are similarities and differences in NIS gene regulation and expression in thyroid and breast cancer. The various agents used to enhance NIS expression, in thyroid and breast cancer will be reviewed with a focus on the mechanism of action. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in 'scan-negative' thyroid cancer and some breast cancer. C1 Yamanashi Univ, Dept Med 3, Yamanashi 4093898, Japan. Univ Calif Los Angeles, David Geffen Sch Med, Mol Endocrinol Lab, VA Greater Los Angeles Healthcare Syst,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Mol Endocrinol Lab, VA Greater Los Angeles Healthcare Syst,Dept Physi, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Yamanashi Univ, Dept Med 3, Yamanashi 4093898, Japan. EM gbrent@ucla.edu FU NCI NIH HHS [R01 CA089364] NR 231 TC 104 Z9 112 U1 0 U2 5 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2006 VL 13 IS 3 BP 797 EP 826 DI 10.1677/erc.1.01143 PG 30 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 103YX UT WOS:000241924200009 PM 16954431 ER PT J AU Moore, K Roubideaux, Y Noonan, C Goldberg, J Shields, R Acton, K AF Moore, Kelly Roubideaux, Yvette Noonan, Carolyn Goldberg, Jack Shields, Ray Acton, Kelly TI Measuring the quality of diabetes care in urban and rural Indian health programs SO ETHNICITY & DISEASE LA English DT Article ID AMERICAN-INDIANS; ALASKA NATIVES AB Objective: The purpose of this study was to compare the quality of diabetes care provided to American Indians/Alaska Natives (AI/AN) by urban and rural Indian health programs. Design: Medical record review data collected by the Indian Health Service as part of the Diabetes Care and Outcomes Audit in 2002. Setting: Seventeen urban Indian health clinics and 225 rural Indian health programs. Patients: All urban AI/AN patients (n = 710) and random sample records of rural AI/AN patients (n = 1420). Main Outcomes Measures: Adherence to guidelines for process measures and intermediate outcomes of diabetes care. Results: Compared to the rural sample, urban patients were more likely to have received diabetes education during the prior year (P <= .05). Annual dental examinations were less common among urban patients than rural patients (19% vs 41%, P <= .001). Completion of laboratory testing and immunizations were similar in both groups. Adjusted mean levels for intermediate outcomes of diabetes care and the percentage achieving recommended levels varied slightly but were not statistically or clinically significant. Conclusions: Few differences in the quality of diabetes care were found between urban and rural Indian health sites. Differences in the receipt of dental examinations may reflect differences in resources and staffing between urban and rural settings. This study serves as a baseline for the assessment of ongoing interventions aimed at improving the quality of care. C1 IHS Div Diabet Treatment & Prevent, Albuquerque, NM USA. Univ Arizona, Coll Publ Hlth, Tucson, AZ USA. Univ Washington, Dept Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Vietnam Era Twin Registry, VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Moore, K (reprint author), 5300 Homestead Rd NE, Albuquerque, NM 87110 USA. EM kelly.moore@ihs.gov FU AHRQ HHS [P01 HS10854]; NIA NIH HHS [P30 AG15297]; NIMHD NIH HHS [P60 MD000507] NR 15 TC 7 Z9 7 U1 2 U2 3 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2006 VL 16 IS 4 BP 772 EP 777 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 094KN UT WOS:000241238400004 PM 17061726 ER PT J AU Hematpour, K Bennett, CJ Rogers, D Head, CS AF Hematpour, Khashayar Bennett, Carol J. Rogers, David Head, Christian S. TI Supraclavicular lymph node: incidence of unsuspected metastatic prostate cancer SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE supraclavicular lymph node; prostate cancer; metastasis ID NECK; HEAD AB An uncommon presentation of prostate carcinoma to the supraclavicular lymph nodes is herein reviewed. With prompt diagnosis and treatment, patient survival can be extended. A high index of suspicion is necessary to make the diagnosis. The clinical features of four cases involving metastatic prostate carcinoma will be discussed. C1 Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90073 USA. Columbia Univ, Coll Phys & Surg, New York, NY 10025 USA. Greater Los Angeles VA Med Syst, Dept Urol, Los Angeles, CA USA. Greater Los Angeles VA Med Syst, Dept Pathol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Otolaryngol, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Bennett, CJ (reprint author), Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, 11301 Wilshire Blvd,Mail Code 10 H2, Los Angeles, CA 90073 USA. EM kh2231@columbia.edu; carol.bennett@med.va.gov; david.rogers5@med.va.gov; chead@mednet.ucla.edu NR 7 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0937-4477 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD SEP PY 2006 VL 263 IS 9 BP 872 EP 874 DI 10.1007/s00405-006-0066-2 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 067JC UT WOS:000239296900015 PM 16830117 ER PT J AU Religa, D Strozyk, D Cherny, RA Volitakis, I Haroutunian, V Naslund, J Winblad, B Bush, AI AF Religa, D. Strozyk, D. Cherny, R. A. Volitakis, I. Haroutunian, V. Naslund, J. Winblad, B. Bush, A. I. TI Positive correlation of brain zinc with Alzheimer's disease amyloid burden SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Karolinska Inst, Neurotec, S-10401 Stockholm, Sweden. Polish Acad Sci, Med Res Ctr, PL-00901 Warsaw, Poland. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Univ Melbourne, Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol,Genet & Aging Res Unit, Charlestown, MA USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 TC 0 Z9 0 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2006 VL 13 SU 2 BP 32 EP 32 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 084HE UT WOS:000240523200104 ER PT J AU Thomas, AV Herl, L Hiltunen, M Jones, PB Tanzi, RE Hyman, BT Berezovska, O AF Thomas, A. V. Herl, L. Hiltunen, M. Jones, P. B. Tanzi, R. E. Hyman, B. T. Berezovska, O. TI Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high throughput fluorescent plate reader SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Lab, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2006 VL 13 SU 2 BP 32 EP 32 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 084HE UT WOS:000240523200105 ER PT J AU Zabagoitia, M Gage, B Juul-Moller, S Persson, M Labovitz, A Baruch, L Horrow, J AF Zabagoitia, M. Gage, B. Juul-Moller, S. Persson, M. Labovitz, A. Baruch, L. Horrow, J. TI Predictors of ischaemic stroke in anticoagulant-treated atrial fibrillation patients in the SPORTIF III and V trials SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Univ Hosp, Molndal, Sweden. AstraZeneca R&D Molndal, Molndal, Sweden. St Louis Univ Hosp, St Louis, MO 63110 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Drexel Univ, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2006 VL 13 SU 2 BP 45 EP 45 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 084HE UT WOS:000240523200144 ER PT J AU El Fakhri, G Guerin, B Sitek, A Curillova, Z Anagnostopoulos, C Dorbala, S Coughlan, M Cantagallo, L Kardan, A Yasuda, T Fischman, A Di Carli, M AF El Fakhri, G. Guerin, B. Sitek, A. Curillova, Z. Anagnostopoulos, C. Dorbala, S. Coughlan, M. Cantagallo, L. Kardan, A. Yasuda, T. Fischman, A. Di Carli, M. TI Absolute myocardial blood flow quantitation in Rb-82 cardiac PET using generalized factor and compartment analysis: A reproducibility study SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Lawrence Berkeley Natl Labs, Berkeley, CA USA. Royal Brompton Hosp, London SW3 6LY, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2006 VL 33 SU 2 BP S217 EP S217 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V43XI UT WOS:000202967400633 ER PT J AU Alpert, JE AF Alpert, J. E. TI Taking remission to the next level SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY OCT 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S581 EP S582 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771302251 ER PT J AU Biederman, J Spencer, TJ Mick, E AF Biederman, J. Spencer, T. J. Mick, E. TI Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S545 EP S546 DI 10.1016/S0924-977X(06)70763-5 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771302170 ER PT J AU Biederman, J Petty, C Hirshfeld-Becker, D Henin, A Henry, B Faraone, SV Rosenbaum, JF AF Biederman, J. Petty, C. Hirshfeld-Becker, D. Henin, A. Henry, B. Faraone, S. V. Rosenbaum, J. F. TI Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. SUNY Upstate Med Univ, Syracuse, NY USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S452 EP S453 DI 10.1016/S0924-977X(06)70590-9 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771301256 ER PT J AU Michelson, D Adler, LA Amsterdam, JD Dunner, DL Nierenberg, AA Reimherr, FW Schatzberg, AF Kelsey, DK Feldman, PD Levine, LR Williams, DW AF Michelson, D. Adler, L. A. Amsterdam, J. D. Dunner, D. L. Nierenberg, A. A. Reimherr, F. W. Schatzberg, A. F. Kelsey, D. K. Feldman, P. D. Levine, L. R. Williams, D. W. TI Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized, double-blind, placebo-controlled study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Washington, Ctr Anxiety & Depress, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Utah, Hlth Sci Ctr, Dept Psychiat, Mood Disorders Clin, Salt Lake City, UT USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S290 EP S291 DI 10.1016/S0924-977X(06)70295-4 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771300285 ER PT J AU Mick, E Biederman, J Spencer, T Faraone, SV Zhang, H AF Mick, E. Biederman, J. Spencer, T. Faraone, S. V. Zhang, H. TI The validity of the quality of life enjoyment and satisfaction questionnaire in adults with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Syracuse, Syracuse, NY USA. McNeil Consumer & Specialty Pharmaceut, Ft Washington, MD USA. NR 2 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S533 EP S533 DI 10.1016/S0924-977X(06)70739-8 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771302146 ER PT J AU Pollack, M AF Pollack, M. TI Issues and challenges around anxiety and depression: co-conspirators for chronicity SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S574 EP S574 DI 10.1016/S0924-977X(06)70822-7 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771302229 ER PT J AU Pollack, M Stein, DJ Mangano, R Entsuah, R Simon, N AF Pollack, M. Stein, D. J. Mangano, R. Entsuah, R. Simon, N. TI Predictors of clinical outcome in panic disorder: a pooled analysis of venlafaxine extended release short-term treatment studies SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. Wyeth Res, Dept Neurosci, Collegeville, PA USA. Wyeth Res, Clin Global Biostat, Collegeville, PA USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S465 EP S466 DI 10.1016/S0924-977X(06)70614-9 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771302021 ER PT J AU Sachs, G AF Sachs, G. TI Major depressive disorder (MDD) and bipolar depression: different diagnoses, same treatment? SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S578 EP S578 DI 10.1016/S0924-977X(06)70834-3 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771302241 ER PT J AU Spencer, TJ Biederman, J Ciccone, P Madras, B Parasrampuria, DA Fischman, AJ Mick, E Martin, J McDonnel, T AF Spencer, T. J. Biederman, J. Ciccone, P. Madras, B. Parasrampuria, D. A. Fischman, A. J. Mick, E. Martin, J. McDonnel, T. TI Pharmacokinetics, detection, likeability and dislikeability of two formulations of long-acting oral methylphenidate SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. McNeil Consumer & Specialty Pharmaceut, McNeil Consumer & Specialty Pharmaceut, Ft Washington, MD USA. New England Primate Res Ctr, Div Neurochem, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S529 EP S529 DI 10.1016/S0924-977X(06)70732-5 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771302139 ER PT J AU Trivedi, MH Fava, M Nierenberg, AA Warden, D Wisniewski, SR Rush, AJ AF Trivedi, M. H. Fava, M. Nierenberg, A. A. Warden, D. Wisniewski, S. R. Rush, A. J. TI Research update from the latest STAR*D findings SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol ID SEQUENCED TREATMENT ALTERNATIVES; RATIONALE C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S331 EP S332 DI 10.1016/S0924-977X(06)70369-8 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771301035 ER PT J AU de Bazelaire, C Rofsky, NM Duhamel, G Zhang, JB Michaelson, MD George, D Alsop, DC AF de Bazelaire, Cedric Rofsky, Neil M. Duhamel, Guillaume Zhang, Jingbo Michaelson, M. Dror George, Daniel Alsop, David C. TI Combined T2* and T1 measurements for improved perfusion and permeability studies in high field using dynamic contrast enhancement SO EUROPEAN RADIOLOGY LA English DT Article DE dynamic contrast enhancement; T2*; tumor; input function ID QUANTITATIVE CEREBRAL PERFUSION; ARTERIAL INPUT FUNCTION; MRI; QUANTIFICATION AB This study analyzed the T2* effect of extracellularly distributed gadolinium contrast agents in arterial blood during tumor studies using T1-weighted sequences at high field strength. A saturation-prepared dual echo sequence with echo times of 1.5 and 3.5 ms was employed at 3 T to simultaneously characterize T1 and T2* of arterial blood during bolus administration of Gd-DTPA in 28 patients with body tumors. T2* effect and T1 effect of Gd-DTPA on image intensity of whole blood were calibrated in human blood samples with different concentrations of contrast agent. T2* was used to estimate concentration near the peak of the bolus. T1 was used to measure lower concentrations when T2* was not significant. T2* was measurable on calibration curves for Gd-DTPA concentrations higher than 4 mM. This concentration was exceeded in 18 patients. The mean signal intensity reduction because of T2* effect was estimated at 22 +/- 14% of the T2* compensated signal. Using T2* measurements reduced underestimations of peak arterial Gd-DTPA concentration (59 +/- 38%) and overestimation of permeability K-trans (58%). The T2* effect of gadolinium contrast agents should therefore be accounted for when performing tumors study with T1-weighted sequences at high field strength. C1 Hop St Louis, Dept Radiol, F-75475 Paris 10, France. Beth Israel Deaconess Med Ctr, Dept Radiol, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP de Bazelaire, C (reprint author), Hop St Louis, Dept Radiol, 1 Ave Claude Vellefaux, F-75475 Paris 10, France. EM cedric.de-bazelaire@sls.aphp.fr RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 NR 21 TC 43 Z9 43 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD SEP PY 2006 VL 16 IS 9 BP 2083 EP 2091 DI 10.1007/s00330-006-0198-1 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 071HK UT WOS:000239590200022 PM 16583215 ER PT J AU Wegiel, B Bjartell, A Liao, JP AF Wegiel, B. Bjartell, A. Persson Liao, J. TI Cyclin A1 is involved in PCa cells invasion via altering expression of VEGF and beta-catenin SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Surg, BIDMC, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA. Lund Univ, Dept Lab Med, Malmo, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD SEP PY 2006 VL 5 IS 14 MA 39 BP 796 EP 796 DI 10.1016/S1569-9056(06)61289-X PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 085TW UT WOS:000240628300040 ER PT J AU Zhang, XH Wojcikiewicz, EP Moy, VT AF Zhang, Xiaohui Wojcikiewicz, Ewa P. Moy, Vincent T. TI Dynamic adhesion of T lymphocytes to endothelial cells revealed by atomic force microscopy SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE T lymphocyte; vascular endothelial cell; atomic force microscopy; cell adhesion ID IN-VIVO; LEUKOCYTE; SPECTROSCOPY; MIGRATION; RECIRCULATION; RECOGNITION; MOLECULE-1; PARADIGM; BONDS AB The recruitment of T lymphocytes to lymphold organs or sites of inflammation is a crucial step in adaptive immunity. These processes require endothelial activation and expression of adhesion molecules, including E- and P-selectins, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). However, the complete characterization of the adhesion strength and dynamics between lymphocytes and endothelial cells has been hampered by the lack of sensitive quantitative techniques. Here we report on the application of atomic force microscopy to characterize the interaction between individual pairs of living T lymphocytes (i.e., Jurkat cells) and human umbilical vein endothelial cells (HUVECs). The detachment of individual cell-cell conjugates was a complex process involving several step-like rupture events and the viscoelastic deformation of cells on the scale of several microns. Adhesion between Jurkat cells and activated endothelial cells increased with compression force and contact time, with the most dramatic changes occurring within the first half second of contact. After 0.25 sec of contact, E-selectin, ICAM-1, and VCAM-1 contributed to 18%, 39%, and 41% of total adhesion strength, respectively, suggesting that ICAM-1 and VCAM-1 contributed more than the selectins in supporting cell attachment. C1 Univ Miami, Sch Med, Dept Physiol, Miami, FL 33136 USA. RP Zhang, XH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM xzhang@cbr.med.harvard.edu; vmoy@miami.edu FU NIGMS NIH HHS [R29 GM055611, GM55611, R01 GM055611, R01 GM055611-07, R01 GM086808] NR 31 TC 46 Z9 46 U1 1 U2 9 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD SEP PY 2006 VL 231 IS 8 BP 1306 EP 1312 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 085TU UT WOS:000240628100004 PM 16946399 ER PT J AU Scadden, DT AF Scadden, D. T. TI Therapeutic manipulation of the stem cell niche SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. Harvard Univ, 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 2 BP 35 EP 35 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500003 ER PT J AU Xu, H Szczur, K Zheng, Y Settleman, J Williams, DA Filippi, MD AF Xu, H. Szczur, K. Zheng, Y. Settleman, J. Williams, D. A. Filippi, M. D. TI Regulation of RhoA activity by p190-B RhoGAP is critical for hematopoietic stem/progenitor cell homing and migration SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Cell & Mol Biol Grad Program, Cincinnati, OH USA. Massachusetts Gen Hosp, Ctr Mol Therapeut, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 95T46 BP 59 EP 59 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500094 ER PT J AU Pritsker, M Lemischka, IR AF Pritsker, M. Lemischka, I. R. TI Experimental reconstruction of molecular networks in embryonic stem cells using large-scale gain-of-function genetic screens SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 99F58 BP 60 EP 60 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500098 ER PT J AU Ritz, J Zorn, E Cutler, C Miklos, DB Soiffer, RJ Antin, JH AF Ritz, J. Zorn, E. Cutler, C. Miklos, D. B. Soiffer, R. J. Antin, J. H. TI Targeting B cells and regulatory T cells for treatment of chronic graft versus host disease SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA USA. Stanford Univ, Sch Med, Stanford, CA 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 120 BP 66 EP 66 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500119 ER PT J AU Barata, JT Silva, A Abecasis, M Carlesso, N Cumano, A Cardoso, AA AF Barata, Joao T. Silva, Ana Abecasis, Miguel Carlesso, Nadia Cumano, Ana Cardoso, Angelo A. TI Molecular and functional evidence for activity of murine IL-7 on human lymphocytes SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SEVERE COMBINED IMMUNODEFICIENCY; RECEPTOR ALPHA-CHAIN; B-LINEAGE CELLS; GROWTH-FACTOR; HUMAN INTERLEUKIN-7; T-CELLS; PROGENITOR CELLS; TRANSGENIC MICE; ORGAN-CULTURE AB Although interleukin-7 (IL-7) is essential for human and murine lymphopoiesis and homeostasis, clear disparities between these species regarding the role of IL-7 during B-cell development suggest that other, subtler differences may exist. One basic unsolved issue of IL-7 biology concerns cross-species activity, because in contrast to the human ortholog, the ability of murine (m)IL-7 to stimulate human cells remains unresolved. Establishing whether two-way cross-species reactivity occurs is fundamental for evaluating the role of IL-7 in chimeric human-mouse models, which are the most versatile tools for studying human lymphoid development and disease in vivo. Here, we show that mIL-7 triggers the same signaling pathways as human (h)IL-7 in human T cells, promoting similar changes in viability, proliferation, size, and immunophenotype, even at low concentrations. This ability is not confined to T cells, because mIL-7 mediates cell growth and protects human B-cell precursors from dexamethasone-induced apoptosis. Importantly, endogenous mIL-7 produced in the mouse thymic microenvironment stimulates human T cells, because their expansion in chimeric fetal thymic organ cultures is inhibited by a mIL-7-specific neutralizing antibody. Our results demonstrate that mIL-7 affects human lymphocytes and indicate that mouse models of human lymphoid development and disease must integrate the biological effects of endogenous IL-7 on human cells. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal. Hosp Santa Cruz, Serv Cardiol Pediat, Carnaxide, Portugal. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenrat Med, Boston, MA 02115 USA. Inst Pasteur, Unit Lymphocyte Dev, Paris, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Barata, JT (reprint author), Univ Lisbon, Fac Med, Inst Mol Med, Ed Egas Moniz,P3C-48,Av Prof Egas Moniz, P-1649028 Lisbon, Portugal. EM joao_barata@fm.ul.pt RI Barata, Joao/D-9181-2015 OI Barata, Joao/0000-0002-4826-8976 NR 60 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 BP 1133 EP 1142 DI 10.1016/j.exphem.2006.05.001 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085JM UT WOS:000240600400001 PM 16939806 ER PT J AU Dewey, RA Diez, IA Ballmaier, M Filipovich, A Greil, J Gungor, T Happel, C Maschan, A Noyan, F Pannicke, U Schwarz, K Snapper, S Welte, K Klein, C AF Dewey, Ricardo A. Diez, Ines Avedillo Ballmaier, Matthias Filipovich, Alexandra Greil, Johann Gungor, Tayfun Happel, Christoph Maschan, Alexey Noyan, Fatih Pannicke, Ulrich Schwarz, Klaus Snapper, Scott Welte, Karl Klein, Christoph TI Retroviral WASP gene transfer into human hematopoietic stem cells reconstitutes the actin cytoskeleton in myeloid progeny cells differentiated in vitro SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; BONE-MARROW-TRANSPLANTATION; SYNDROME PROTEIN; FUNCTIONAL CORRECTION; X-CHROMOSOME; T-CELLS; EXPRESSION; DEFECTS; LEADS; POLYMERIZATION AB Objective. Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder characterized by recurrent infections, autoimmunity, microthrombocytopenia, and susceptibility to malignant tumors. Compared with the conventional treatment using allogeneic bone marrow transplantation, hematopoietic stem cell gene therapy might offer more specific and less toxic therapeutic options. Methods. We investigated retroviral WAS protein (WASP) gene transfer to assess functional correction and potential toxicities in human CD34(+) cells from WAS patients and healthy individuals, respectively. Results. WASP mRNA and protein levels were restored in CD14(+) cells derived from WASP-transduced hematopoietic stem cells. Functional reconstitution in WASP-transduced myeloid cells was documented by podosome formation and Fc gamma R-mediated phagocytosis. Importantly, overexpression of WASP in CD34(+) cells from healthy donors did not cause any discernible toxic effects. Conclusions. Our studies document the feasibility of WASP gene transfer into human CD34(+) cells and suggest that the phenotype of WASP-deficient myeloid cells can be restored upon retroviral gene transfer. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Hannover Med Sch, Dept Pediat Hematol & Oncol, D-30625 Hannover, Germany. Cincinnati Childrens Hosp, Med Ctr, Div Hematol & Oncol, Cincinnati, OH USA. Univ Tubingen, Childrens Hosp, Dept Pediat, Tubingen, Germany. Univ Zurich, Childrens Hosp, Div Immunol, Zurich, Switzerland. Res Inst Pediat Hematol, Moscow, Russia. Inst Clin Transfus Med & Immunogenet, Ulm, Germany. Univ Hosp Ulm, Dept Transfus Med, Ulm, Germany. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol & Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM Klein.Christoph@mh-hannover.de OI Happel, Christoph/0000-0002-1010-4327 NR 30 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 BP 1162 EP 1170 DI 10.1016/j.exphem.2006.04.021 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085JM UT WOS:000240600400004 ER PT J AU Saito, TI Rubio, MT Sykes, M AF Saito, Toshiki I. Rubio, Marie T. Sykes, Megan TI Clinical relevance of recipient leukocyte infusion as antitumor therapy following nonmyeloablative allogeneic hematopoietic cell transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSION; VERSUS-HOST-DISEASE; DENDRITIC CELLS; IFN-GAMMA; CHIMERAS; LEUKEMIA; TUMOR; CANCER; CD40 AB Objective. Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained remissions of advanced, chemorefractory hematologic malignancies. In murine mixed chimeras prepared with nonmyeloablative conditioning, we previously showed that recipient leukocyte infusions (RLIs) induce loss of donor chimerism and mediate antitumor responses against host-type tumors. We assessed the clinical relevance of our mouse model. Methods. Mixed chimeric mice were generated by a nonmyeloablative protocol and some of them received host-derived tumor cells and/or RLIs or donor lymphocyte infusion (DLI). We examined chimerism, graft-versus-host disease (GVHD), and tumor survival. Results. RLI is still effective when the leukocytes are obtained from tumor-bearing mice. Established mixed chimerism is required prior to the induced rejection to achieve maximum antitumor effects. The antitumor effects of RLI are not dependent on a specific donor strain or conditioning protocol. In contrast to DLI, RLI leads to donor cell rejection without the risk of GVHD. Conclusion. Together, these data reinforce the clinical potential of RLI therapy as a new HCT strategy that does not carry the risk of GVHD. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149,5102 13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [R01 CA079989] NR 28 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 BP 1271 EP 1277 DI 10.1016/j.exphem.2006.04.022 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085JM UT WOS:000240600400015 PM 16939820 ER PT J AU Malik, RA Veves, A Tesfaye, S AF Malik, R. A. Veves, A. Tesfaye, S. TI Ameliorating human diabetic neuropathy: Lessons from implanting hematopoietic mononuclear cells SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material ID ALDOSE REDUCTASE INHIBITOR; ALPHA-LIPOIC ACID; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; PERIPHERAL-NERVE FUNCTION; GLYCATION END-PRODUCTS; CRITICAL LIMB ISCHEMIA; GROWTH-FACTOR-I; SURAL-NERVE; C-PEPTIDE C1 Univ Manchester, Div Cardiovasc & Endocrine Sci, Manchester, Lancs, England. Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02114 USA. Royal Hallamshire Hosp, Diabet Res Unit, Sheffield S10 2JF, S Yorkshire, England. RP Malik, RA (reprint author), Univ Manchester, Div Cardiovasc & Endocrine Sci, Manchester, Lancs, England. EM Rayaz.a.malik@man.ac.uk OI Malik, Rayaz/0000-0002-7188-8903 NR 99 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2006 VL 201 IS 1 BP 7 EP 14 DI 10.1016/j.expneurol.2006.04.027 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 079CC UT WOS:000240152100002 PM 16808913 ER PT J AU Ott, HC Taylor, DA AF Ott, Harald C. Taylor, Doris A. TI From cardiac repair to cardiac regeneration - ready to translate? SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE cardiac regeneration; cardiac repair; cardiac stem cells; cell therapy; cellular cardiomyoplasty; heart failure ID ACUTE MYOCARDIAL-INFARCTION; ENDOTHELIAL PROGENITOR CELLS; SKELETAL MYOBLAST TRANSPLANTATION; BONE-MARROW-CELLS; VENTRICULAR ASSIST DEVICES; ISCHEMIC-HEART FAILURE; MESENCHYMAL STEM-CELLS; LONG-TERM SURVIVAL; FOLLOW-UP; SATELLITE CELL AB Cardiovascular disease is a major public health challenge in the western world. Mortality of acute events has improved, but more patients develop HF - a condition affecting up to 22 million people worldwide. Cell transplantation is the first therapy to attempt replacement of lost cardiomyocytes and vasculature to restore lost contractile function. Since the first reported functional repair after injection of autologous skeletal myoblasts into the injured heart in 1998, a variety of cell types have been proposed for transplantation in different stages of cardiovascular disease. Fifteen years of preclinical research and the rapid move into clinical studies have left us with promising results and a better understanding of cells as a potential clinical tool. Cell-based cardiac repair has been the first step, but cardiac regeneration remains the more ambitious goal. Promising new cell types and the rapidly evolving concept of adult stem and progenitor cell fate may enable us to move towards regenerating viable and functional myocardium. Meeting a multidisciplinary consensus will be required to translate these findings into safe and applicable clinical tools. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Minnesota, Ctr Cardiovasc Repair, Minneapolis, MN 55455 USA. RP Taylor, DA (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM dataylor@umn.edu NR 150 TC 9 Z9 10 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2006 VL 6 IS 9 BP 867 EP 878 DI 10.1517/14712598.6.9.867 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 081SC UT WOS:000240336300002 PM 16918254 ER PT J AU Raje, N Hideshima, T Anderson, KC AF Raje, Noopur Hideshima, Teru Anderson, Kenneth C. TI Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE actimid; immunomodulatory drugs; lenalidomide; multiple myeloma; thalidomide; treatment ID THALIDOMIDE PLUS DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; NF-KAPPA-B; MOLECULAR-MECHANISMS; COMBINATION THERAPY; ORAL MELPHALAN; CELLS; ANALOGS; ANGIOGENESIS; ACTIVATION AB Immunomodulatory drugs, such as thalidomide, lenalidomide (Revlimid(R), CC-5013) and actimid (CC-4047), have a broad spectrum of activity and have shown remarkable responses in patients with multiple myeloma and related hematological diseases, such as myelodysplastic syndrome. They are currently being tested in other cancer types. This review will focus on the preclinical and clinical activity of thalidomide and its more potent immunomodulatory derivatives that are used to treat multiple myeloma. They represent a new class of antitumor agents that not only target the tumor cell directly, but also have significant activity within the bone marrow milieu. These agents have shown high responses in all phases of multiple myeloma, including the upfront setting, relapsed refractory stage and also as maintenance therapy for the disease. They have been used in combination with dexamethasone, chemotherapy and, more recently, with other novel agents, such as proteasome inhibitors. Thalidomide and lenalidomide in combination with dexamethasone have recently been approved by the US FDA for the treatment of multiple myeloma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Cox 813,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org NR 59 TC 12 Z9 12 U1 0 U2 4 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD SEP PY 2006 VL 6 IS 9 BP 1239 EP 1247 DI 10.1586/14737140.6.9.1239 PG 9 WC Oncology SC Oncology GA 093XD UT WOS:000241202700017 PM 17020458 ER PT J AU Morello, AM Januzzi, JL AF Morello, Angelo M. Januzzi, James L. TI Amino-terminal pro-brain natriuretic peptide: a biomarker for diagnosis, prognosis and management of heart failure SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE BNP; brain natriuretic peptide; heart failure; natriuretic peptides; NT-proBNP ID LEFT-VENTRICULAR DYSFUNCTION; EMERGENCY-DEPARTMENT PRIDE; CORONARY-ARTERY-DISEASE; ACUTE PULMONARY-EMBOLISM; ST-SEGMENT ELEVATION; NT-PROBNP; MYOCARDIAL-INFARCTION; SYSTOLIC FUNCTION; RISK STRATIFICATION; EJECTION FRACTION AB There is a substantial need for a diagnostic tool to aid in the early diagnosis of heart failure and in the recognition of those at risk for its development, as well as in guidance of therapy. Testing for amino-terminal pro-brain natriuretic peptide (NT-proBNP) has been recognized to have utility in the diagnosis, prognosis and management of heart failure. In addition, numerous other applications for NT-proBNP testing are now recognized, such as evaluation of patients with heart disease in the absence of heart failure, as well as the diagnostic and prognostic evaluation of patients with acute coronary syndromes or pulmonary thromboembolism. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org NR 101 TC 4 Z9 5 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2006 VL 6 IS 5 BP 649 EP 662 DI 10.1586/14737159.6.5.649 PG 14 WC Pathology SC Pathology GA 093AA UT WOS:000241138300001 PM 17009901 ER PT J AU Xu, RJ Jin, JF Hu, W Sun, W Bielawski, J Szulc, Z Taha, T Obeid, LM Mao, CG AF Xu, Ruijuan Jin, Junfei Hu, Wei Sun, Wei Bielawski, Jacek Szulc, Zdzislaw Taha, Tarek Obeid, Lina M. Mao, Cungui TI Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P SO FASEB JOURNAL LA English DT Article DE placenta; rate-limiting step; serum deprivation; S1P receptor; sphingolipid ID PROTEIN-COUPLED RECEPTORS; MOLECULAR-CLONING; NEUTRAL CERAMIDASE; FUNCTIONAL-CHARACTERIZATION; SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE; OVARIAN-CANCER; EDG-1 FAMILY; GENE FAMILY; SPHINGOSINE-1-PHOSPHATE AB Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, promotes cell proliferation and survival whereas its precursor, sphingosine, has the opposite effects. However, much remains unknown about their regulation. Here we identify a novel human ceramidase (haCER2) that regulates the levels of both sphingosine and S1P by controlling the hydrolysis of ceramides. haCER2 is localized to the Golgi complex and is highly expressed in the placenta. High ectopic expression of haCER2 caused fragmentation of the Golgi complex and growth arrest in HeLa cells due to sphingosine accumulation. Low ectopic expression of haCER2 increased S1P without sphingosine accumulation, promoting cell proliferation in serum-free medium. This proliferative effect was suppressed by dimethylsphingosine, an inhibitor of the S1P formation, or by the RNA interference (RNAi) - mediated inhibition of S1P(1), a G-protein-coupled receptor for S1P. The RNAi-mediated down-regulation of haCER2 enhanced the serum deprivation-induced growth arrest and apoptosis of HeLa cells, which was inhibited by addition of exogenous S1P. Serum deprivation up-regulated both haCER2 mRNA and activity in HeLa cells. haCER2 mRNA is also up-regulated in some tumors. Taken together, these results suggest that haCER2 is important for the generation of S1P and S1P-mediated cell proliferation and survival, but that its overexpression may cause cell growth arrest due to an accumulation of sphingosine. - Xu, R., Jin, J., Hu, W., Sun, W., Bielawski, J., Szulc, Z., Taha, T., Obeid, L. M., Mao, C. Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. RP Mao, CG (reprint author), 114 Doughty St,Rm 646,STB,POB 250779, Charleston, SC 29425 USA. EM maoc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [R01 CA104834]; NCRR NIH HHS [P20RR017677] NR 48 TC 71 Z9 74 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2006 VL 20 IS 11 BP 1813 EP 1825 DI 10.1096/fj.05-5689com PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RZ UT WOS:000240267000009 PM 16940153 ER PT J AU Abusief, ME Missmer, SA Ginsburg, ES Weeks, JC Winer, EP Partridge, AH AF Abusief, M. E. Missmer, S. A. Ginsburg, E. S. Weeks, J. C. Winer, E. P. Partridge, A. H. TI Chemotherapy-related amenorrhea in premenopausal women with breast cancer: The effect of paclitaxel, dose density and trastuzumab. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S194 EP S194 DI 10.1016/j.fertnstert.2006.07.514 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500463 ER PT J AU Digirolamo, CM Kashiwagi, A Shioda, T Hansen, T Pru, J AF Digirolamo, C. M. Kashiwagi, A. Shioda, T. Hansen, T. Pru, J. TI Mechanisms regulating uterine steroidogenesis at the maternal: Embryonic interface. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Mol Profiling Lab, Boston, MA 02114 USA. Colorado State Univ, Coll Vet Med & Biomed Sci, Anim Reprod & Biotechnol Lab, Ft Collins, CO 80523 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S339 EP S340 DI 10.1016/j.fertnstert.2006.07.923 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501318 ER PT J AU Kashiwagi, A Pru, JK AF Kashiwagi, A. Pru, J. K. TI Impact of the endocrine disruptor 7,12-dimethylbenz[A]anthracene on uterine decidualization and pregnancy maintenance. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Harvard Med Sch, 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 MA P1029 BP S515 EP S515 DI 10.1016/j.fertnstert.2006.07.1431 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038502291 ER PT J AU Luk, J Petrozza, J AF Luk, J. Petrozza, J. TI Evaluation of compliance and range of fees by ASRM listed EGG donor and subrogacy agencies. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S190 EP S190 DI 10.1016/j.fertnstert.2006.07.503 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500453 ER PT J AU Styer, AK Wolkovich, AM Veiga, C Wright, DL Toth, TL AF Styer, A. K. Wolkovich, A. M. Veiga, C. Wright, D. L. Toth, T. L. TI Implementation of elective single blastocyst transfer significantly decreases the incidence of multiple gestation without affecting overall and clinical pregnancy rates compared to double blastocyst transfer. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Fertil Ctr, Harvard Med Sch, Dept Obstet Gynecol, 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S111 EP S111 DI 10.1016/j.fertnstert.2006.07.298 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500260 ER PT J AU Zelinski, MB Pau, F Murphy, M Lawson, M Fanton, J Tilly, J AF Zelinski, M. B. Pau, F. Murphy, M. Lawson, M. Fanton, J. Tilly, J. TI Intraovarian delivery of sphingosine-1-phosphate (S1P) protects ovarian follicles from X-irradiation damage in rhesus monkeys. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod Sci, Beaverton, OR USA. Pacific NW Natl Lab, Battelle Labs, Richland, WA 99352 USA. Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Dept Surg, Beaverton, OR USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod, 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S95 EP S95 DI 10.1016/j.fertnstert.2006.07.254 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500222 ER PT J AU Wang, YM Qiao, M Mieyal, JJ Asmis, LM Asmis, R AF Wang, Yanmei Qiao, Mu Mieyal, John J. Asmis, Lars M. Asmis, Reto TI Molecular mechanism of glutathione-mediated protection from oxidized low-density lipoprotein-induced cell injury in human macrophages: Role of glutathione reductase and glutaredoxin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE macrophage; atherosclerosis; cell death; glutathione; glutaredoxin; glutathione reductase ID MONOCYTE-DERIVED MACROPHAGES; ATHEROSCLEROTIC PLAQUES; LIPID HYDROPEROXIDE; OXIDATIVE INJURY; HUMAN ATHEROMA; APOPTOSIS; DEATH; IRON; TOXICITY; EXPRESSION AB Macrophage death is a hallmark of advanced atherosclerotic plaque, and oxidized low-density lipoprotein (OxLDL) found in these lesions is believed to contribute to macrophage injury. However, the underlying mechanisms of this phenomenon are only poorly understood. Here we show that in human monocyte-derived macrophages, OxLDL depleted intracellular glutathione (GSH) and inhibited glutathione reductase, resulting in a marked diminution of the glutathione/glutathione disulfide ratio. In the absence of OxLDL, an 80% depletion of intracellular GSH levels did not affect cell viability, but glutathione depletion dramatically increased OxLDL-induced cell death. Conversely, supplementation of intracellular GSH stores with glutathione diethyl ester substantially diminished OxLDL toxicity. OxLDL also promoted protein-S-glutatbionylation, which was increased in macrophages pretreated with the glutathione reductase inhibitor BCNU. Knockdown experiments with siRNA directed against glutathione reductase and glutaredoxin showed that both enzymes are essential for the protection of macrophages against OxLDL. Finally, the peroxyl-radical scavenger Trolox did not prevent GSH depletion but completely blocked OxLDL-induced protein-S-glutathionylation and cell death. These data suggest that OxLDL promotes ROS formation and protein-S-glutathionylation by a mechanism independent from its effect on GSH depletion. Neither mechanism was sufficient to induce macrophage injury, but when stimulated concurrently, these pathways promoted the accumulation of protein-glutathione mixed disulfides and cell death. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, San Antonio, TX 78229 USA. Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40506 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. Univ Zurich Hosp, Div Hematol, CH-8091 Zurich, Switzerland. RP Asmis, R (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, 7703 Floyd Curl Dr,MSC 7882, San Antonio, TX 78229 USA. EM asmis@uthscsa.edu FU NHLBI NIH HHS [HL-70963]; NIA NIH HHS [AG-024413] NR 39 TC 36 Z9 36 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2006 VL 41 IS 5 BP 775 EP 785 DI 10.1016/j.freeradbiomed.2006.05.029 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 079YK UT WOS:000240213600010 PM 16895798 ER PT J AU Ying, WH AF Ying, Weihai TI NAD(+) and NADH in cellular functions and cell death SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE NAD(+); NADH; cell death; aging; mitochondria; calcium; review ID NICOTINAMIDE-ADENINE-DINUCLEOTIDE; DELETERIOUS NETWORK HYPOTHESIS; CYCLIC ADP-RIBOSE; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; MITOCHONDRIAL PERMEABILITY TRANSITION; DEPENDENT HISTONE DEACETYLASE; PERINATAL BRAIN-INJURY; NITRIC-OXIDE SYNTHASE; DNA-DAMAGE; CEREBRAL-ISCHEMIA AB Increasing evidence has indicated that NAD(+) and NADH play critical roles not only in energy metabolism, but also in cell death and various cellular functions including regulation of calcium homeostasis and gene expression. It has also been indicated that NAD(+) and NADH are mediators of multiple major biological processes including aging. NAD(+) and NADH produce the biological effects by regulating numerous NAD(+)/NADH-dependent enzymes, including dehydrogenases, poly(ADP-ribose) polymerases, Sir2 family proteins (sirtuins), mono(ADP-ribosyl) transferases, and ADP-ribosyl cyclases. Of particular interest, NAD(+)-dependent generation of ADP-ribose, cyclic ADP-ribose and O-acetyl-ADP-ribose can mediate calcium homeostasis by affecting TRPM2 receptors and ryanodine receptors; and sirtuins and PARPs appear to play key roles in aging, cell death and a variety of cellular functions. It has also been indicated that NADH and NAD(+) can be transported across plasma membranes of cells, and that extracellular NAD(+) may be a new signaling molecule. Our latest studies have shown that intranasal NAD(+) administration can profoundly decrease ischemic brain damage. These new pieces of information have fundamentally changed our understanding about NAD(+) and NADH, suggesting novel paradigms about the metabolism and biological activities of NAD(+) and NADH. Based on this information, it is tempted to hypothesize that NAD(+) and NADH, together with ATP and Ca2+, may be four most fundamental components in life, which can significantly affect nearly all major biological processes. Future studies on NAD(+) and NADH may not only elucidate some fundamental mysteries in biology, but also provide novel insights for interfering aging and many disease processes. C1 San Francisco VA Med Ctr, Dept Neurol 127, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Ying, WH (reprint author), San Francisco VA Med Ctr, Dept Neurol 127, 4150 Clement St, San Francisco, CA 94121 USA. EM Weihai.Ying@ucsf.edu NR 187 TC 102 Z9 107 U1 0 U2 29 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD SEP 1 PY 2006 VL 11 BP 3129 EP 3148 DI 10.2741/2038 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 040ML UT WOS:000237382800097 PM 16720381 ER PT J AU Lugea, A Nan, L French, SW Bezerra, JA Gukovskaya, AS Pandol, SJ AF Lugea, Aurelia Nan, Li French, Samuel W. Bezerra, Jorge A. Gukovskaya, Anna S. Pandol, Stephen J. TI Pancreas recovery following cerulein-induced pancreatitis is impaired in plasminogen-deficient mice SO GASTROENTEROLOGY LA English DT Article ID ACUTE NECROTIZING PANCREATITIS; RENAL INTERSTITIAL FIBROSIS; INDUCED PULMONARY-FIBROSIS; KAPPA-B ACTIVATION; EXTRACELLULAR-MATRIX; STELLATE CELLS; LIVER-INJURY; CELLULAR-LOCALIZATION; FIBRINOLYTIC SYSTEM; IN-VITRO AB Background & AIMS: The plasminogen (plg) system participates in tissue repair in several organs, but its role in pancreas repair remains poorly characterized. To understand better the role of plg in pancreas recovery following injury, we examined the course of cerulein-induced pancreatitis in plg-deficient and -sufficient mice. Methods: Pancreatitis was induced by cerulein administration (50 mu g/kg, 7 intraperitoneal injections). Mice were killed either at the acute phase (7 hours after the first cerulein injection) or during recovery (at 2, 4, and 7 days). in pancreatic sections, we examined pancreatic morphology, trypsin activation, inflammatory cell infiltration, acinar cell death, cell proliferation, extracellular matrix deposition, activation of stellate cells (PSCs), and components of the plg and metalloproteinase systems. Results: In plg-sufficent mice, pancreatic plg levels and plasmin activity increased during the acute phase and remained elevated during recovery. Pancreatitis resolved in plg-sufficient mice within 7 days. Pancreas recovery involved reorganization of the parenchyma structure, removal of necrotic debris, cell proliferation, transient activation of PSCs, and moderate deposition of extracellular matrix proteins. Acute pancreatitis (7 hours) was indistinguishable between plg-deficient and -sufficient mice. In contrast, pancreas recovery was impaired in plg-deficient mice. Pig deficiency led to disorganized parenchyma, extensive acinar cell loss, poor removal of necrotic debris, reduced cell proliferation, and fibrosis. Fibrosis was characterized by deposition of collagens and fibronectin, persistent activation of PSCs, and up-regulation of pancreatic transforming growth factor beta 1. Conclusions: Plg/plasmin deficiency leads to features similar to those found in chronic pancreatitis such as parenchyma 1 atrophy and fibrosis. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, USC, Res Ctr Alcoholic Liver & Pancreat Dis, Los Angeles, CA 90073 USA. Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. Univ Cincinnati, Childrens Hosp, Res Fdn, Cincinnati, OH USA. RP Lugea, A (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, USC, Res Ctr Alcoholic Liver & Pancreat Dis, Bldg 258,Room 339,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM alugea@ucla.edu FU NIAAA NIH HHS [R21 AA015781-01A1, R21AA15781-01A1, R21 AA015781, P50 AA011999]; PHS HHS [P50-A11999] NR 70 TC 25 Z9 25 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2006 VL 131 IS 3 BP 885 EP 899 DI 10.1053/j.gastro.2006.06.023 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 084VF UT WOS:000240561800026 PM 16952557 ER PT J AU Goessling, W Mayer, RJ AF Goessling, Wolfram Mayer, Robert J. TI Systemic treatment of patients who have colorectal cancer and inflammatory bowel disease SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; POPULATION-BASED COHORT; III COLON-CANCER; FLUOROURACIL-BASED CHEMOTHERAPY; RANDOMIZED PHASE-III; CROHNS-DISEASE; ULCERATIVE-COLITIS; FACTOR RECEPTOR; 1ST-LINE TREATMENT; ADJUVANT TREATMENT AB Inflammatory bowel disease (IBD) is an acknowledged predisposing factor for the development of intestinal and extraintestinal cancers. In general, an increased risk for colorectal cancer exists for patients who have both ulcerative colitis (UC) and Crohn's disease (CD). Small bowel tumors are extremely rare in the general population, but their incidence is enhanced 40-fold in patients who have CD. UC confers a marginally increased risk for myeloid leukemia, whereas patients who have CD may have a trend toward a higher incidence of lymphoma. This article reviews the therapeutic options for the most common malignant complication, colorectal carcinoma, as well as specific recommendations regarding the impact of the underlying disease upon the tolerance and efficacy of chemotherapy in these patients. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM robert_mayer@dfci.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 NR 90 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2006 VL 35 IS 3 BP 713 EP + DI 10.1016/j.gtc.2006.07.006 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 088UP UT WOS:000240836900011 PM 16952747 ER PT J AU Sonnenberg, A AF Sonnenberg, Anmon TI Is endoscopic screening before major surgical procedures warranted? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; PREVALENCE AB Background: Gastroenterologists are frequently requested to perform endoscopic procedures to rule out cancer or other serious GI disease before major surgical operations. Objective: To assess whether such requests are warranted. Design: Cost benefit analysis by using decision tree and threshold analysis. Patients: Subjects scheduled for liver and kidney transplant or other major surgeries. Main Outcome Measurements: Costs of medical and surgical procedures. The threshold value is defined as the a priori probability for a GI diagnosis, where the benefit of endoscopy changes from unfavorable to favorable as the diagnostic probability increases. Results: For all types of organ transplants, the threshold probability for diagnosing a GI disease by endoscopy is lower than 1%. Such a low threshold suggests that if a disease cannot be ruled out with certainty before transplant operations or any other major surgical operation, endoscopic screening would be warranted. For lesser interventions, such as percutaneous transluminal coronary angioplasty and coronary bypass grafting, the threshold value varies between 3.2% and 6.5%, which suggests that endoscopic screening may be justified if there are sufficient grounds to suspect a comorbid medical condition that could compromise the success of the planned surgical intervention. Limitations: The model only considers procedure costs and assumes no endoscopic complications. Conclusions: Endoscopic screening before costly and invasive surgical or other medical interventions is justified. C1 Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2006 VL 64 IS 3 BP 375 EP 378 DI 10.1016/j.gie.2006.04.030 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 081GC UT WOS:000240304200013 PM 16923485 ER PT J AU Pai, RD Fong, DG Bundga, ME Odze, RD Rattner, DW Thompson, CC AF Pai, Reina D. Fong, Derek G. Bundga, Michele E. Odze, Robert D. Rattner, David W. Thompson, Christopher C. TI Transcolonic endoscopic cholecystectomy: a NOTES survival study in a porcine model SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; SURGERY AB Background: Transgastric cholecystectomy is a natural orifice transluminal endoscopic surgery (NOTES) procedure that has been reported in 2 nonsurvival studies. Both studies detail substantial technical limitations, with only a 33% success rate when limited to 1 gastric incision site, despite the use of a multichannel locking endoscope. Objective: The aim of this study was to evaluate the feasibility and technical limitations of transcolonic cholecystectomy in a survival model. Design: Animal feasibility study. Interventions: Five pigs, under general anesthesia, were prepared with tap-water enemas, a peranal antibiotic lavage, and a Betadine rinse. A dual-channel endoscope was advanced into the peritoneum through an anterior, transcolonic incision 15 to 20 cm from the anus. After cystic duct and artery ligation, dissection of the gallbladder was achieved by using grasping and cutting instruments. After removing the gallbladder, the colonic incision was closed by using Endoloops and/or endoclips. The animals lived for 2 weeks after the procedure, then they were euthanized, and a necropsy was performed. Results: All 5 gallbladders were successfully resected. Four of the 5 animals flourished in the postoperative period, with appropriate weight gain. In 1 animal, complete closure of the colonic incision was not possible, and it was euthanized at 48 hours for suspected peritonitis. Conclusions: This study reports the first transcolonic organ resection and demonstrates the first successful NOTES cholecystectomy in a survival model. The transcolonic approach provided improved endoscope stability and biliary exposure compared with the transgastric route, and complete incision closure appeared critical for procedural success. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 251 Z9 269 U1 1 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2006 VL 64 IS 3 BP 428 EP 434 DI 10.1016/j.gie.2006.06.079 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 081GC UT WOS:000240304200023 PM 16923495 ER PT J AU Hoshino, K Kimura, T De Grand, AM Yoneyama, R Kawase, Y Houser, S Ly, HQ Kushibiki, T Furukawa, Y Ono, K Tabata, Y Frangioni, JV Kita, T Hajjar, RJ Hayase, M AF Hoshino, K. Kimura, T. De Grand, A. M. Yoneyama, R. Kawase, Y. Houser, S. Ly, H. Q. Kushibiki, T. Furukawa, Y. Ono, K. Tabata, Y. Frangioni, J. V. Kita, T. Hajjar, R. J. Hayase, M. TI Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres SO GENE THERAPY LA English DT Article DE therapeutic; gelatin microspheres; cardiac delivery; angiogenesis ID FIBROBLAST-GROWTH-FACTOR; PRESSURE-REGULATED RETROINFUSION; MYOCARDIAL-INFARCTION; PROGENITOR CELLS; CORONARY SINUS; HEART-FAILURE; GENE DELIVERY; STEM-CELLS; ANGIOGENESIS; ISCHEMIA AB Gelatin hydrogel microspheres (GHMs) have been reported as novel non-viral vectors for gene or protein delivery ( GHM therapy). However, the components of an effective catheter-based delivery strategy for GHM therapy are unknown. We evaluated the effectiveness of three catheter- based strategies for cardiac GHM therapy: (1) antegrade injection (AI) via coronary arteries; (2) retrograde injection (RI) via coronary veins; and (3) direct myocardial injection (DI) via the coronary sinus. AI distributed microspheres homogeneously throughout the target area with 73 +/- 11% retention. RI scattered microspheres non-homogenously with 22 +/- 8% retention. DI distributed microspheres in the needle- advanced area with 47 +/- 14% retention. However, despite high efficiency, AI did not show biological effects of inducing angiogenesis from basic fibroblast growth factor bound to GHMs. Furthermore, focal micro-infarctions, owing to micro-embolism of aggregated GHMs into small coronary arterioles, were detected in the AI group. Conversely, only RI and DI groups displayed increased coronary flow reserve. DI groups also demonstrated increased capillary density. These results suggest that RI and DI are effective for cardiac GHM therapy, while AI appears inappropriate owing to the risk of focal infarctions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Mol Imaging Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Kyoto Univ, Inst Frontier Med Sci, Kyoto, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. RP Hoshino, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Bulfinch 161, Boston, MA 02114 USA. EM kozo@kuhp.kyoto-u.ac.jp FU NHLBI NIH HHS [R01-HL-78691] NR 34 TC 26 Z9 26 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 2006 VL 13 IS 18 BP 1320 EP 1327 DI 10.1038/sj.gt.3302793 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 080HG UT WOS:000240237900002 PM 16708077 ER PT J AU Onitilo, AA Nietert, PJ Egede, LE AF Onitilo, Adedayo A. Nietert, Paul J. Egede, Leonard E. TI Effect of depression on all-cause mortality in adults with cancer and differential effects by cancer site SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE depression; cancer; health survey; death; mood disorder ID NATIONAL DEATH INDEX; BREAST-CANCER; MAJOR DEPRESSION; DIAGNOSIS; DISEASE; WOMEN; SURVIVAL; RISK; CARCINOMA; SYMPTOMS AB Objective: The objective of this study was to compare the effect of depression on the risk of death in adults with and without cancer and by specific cancer site among those with cancer. Research Design and Methods: We analyzed data on 10,025 participants in the population-based National Health and Nutrition Examination Survey (NHANES) 1 Epidemiologic Follow-up Study. Four groups were created based on cancer and depression status in 1982: (a) no cancer, no depression (reference group; no CA, no DEP); (b) depression but no cancer (DEP, no CA); (c) cancer but no depression (CA, no DEP); and (d) cancer and depression (CA+DEP). Six CA sites were defined: lung, breast, gastrointestinal (GI), genitourinary (GU), skin and other. Cox proportional models were used to calculate adjusted hazard for death for each group compared with the reference group and by cancer site. Results: Over 8 years (78,433 person-years of follow-up), 1925 deaths were documented. The mortality rate per 1000 person-years of follow-up was highest in the CA+DEP group. Compared to the reference group, the hazard ratios (HRs) for all-cause mortality were as follows: CA, no DEP: 1.43 [95% confidence interval (95% CI)=1.23-1.67]; DEP, no CA: 1.44 (95% CI= 1.28-1.63); CA+DEP: 1.87 (95% CI=1.49-2.34). HRs for depression by site were as follows: lung: 1.30 (95% CI=0.49-3.99); breast: 1.27 (95% CI=0.58-2.79); GI: 1.47 (95% CI=0.58-3.75); GU: 0.93 (95% CI=0.50-1.74); skin: 1.07 (95% CI=0.67-1.69); other: 2.13 (95% CI=0.55-8.25). Conclusion: The coexistence of cancer and depression is associated with a significantly increased risk of death, and the effect of depression on the risk of death differs by cancer site. (c) 2006 Elsevier Inc. All rights reserved. C1 Marshfield Clin Wausau Ctr, Dept Hematol Oncol, Wausau, WI 54401 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Med Univ S Carolina, Div Gen Internal Med, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston VA TREP, Charleston, SC 29401 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Disparities Res, Charleston, SC 29425 USA. EM egedel@musc.edu OI Nietert, Paul/0000-0002-3933-4986 NR 59 TC 63 Z9 65 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2006 VL 28 IS 5 BP 396 EP 402 DI 10.1016/j.genhosppsych.2006.05.006 PG 7 WC Psychiatry SC Psychiatry GA 086SO UT WOS:000240693500005 PM 16950374 ER PT J AU Roy-Byrne, PP Noonan, C Afari, N Buchwald, D Goldberg, J AF Roy-Byrne, Peter P. Noonan, Carolyn Afari, Niloofar Buchwald, Dedra Goldberg, Jack TI Is the association between posttraumatic stress disorder symptoms and poor health due to a common familial or genetic factor? SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; poor health; familial; genetic; twin ID PRIMARY-CARE PATIENTS; SELF-REPORTED HEALTH; ENVIRONMENTAL CONTRIBUTIONS; FUNCTIONAL IMPAIRMENT; ANXIETY DISORDERS; COSTS; WOMEN; TWIN; DEPRESSION; MORTALITY AB Objective: The objective of this study was to identify genetic, familial and environmental contributions to the association between posttraumatic stress disorder (PTSD) symptoms and poor health. Methods: A community sample of 1852 twin pairs was assessed for symptoms of PTSD [with the Impact of Events Scale (IES)] and self-reported global health status using a single five-level question. An ordinal logistic regression model estimated odds ratio/s (OR) for the association between PTSD and health status. Within-pair analysis assessed confounding by familial and genetic factors and adjusted for the possible confounding influence of age, sex, race, education and self-reported physician diagnosis of depression. Results: The IES was strongly and significantly associated with self-reported health [OR= 1.8; 95% confidence interval (95% CI)=1.5-2.2; highest quartile vs. lowest quartile]. This association remained significant in within-pair analysis (OR= 1.3; 95% CI= 1.0-1.7), but after further adjustment for sociodemographics and depression, it was no longer significant (P-trend=.17). Separate analysis by zygosity did not show differential effect in monozygotic or dizygotic pairs. Conclusion: These findings suggest that the association between PTSD symptoms and poor health is, in part, due to familial confounding and sociodemographic factors. Little evidence of confounding by genetic factors was found. These findings suggest that early prevention efforts would have the greatest potential for improving poor health in PTSD-prone patients, whereas later intervention efforts directed at treating PTSD may have a more limited impact on improving poor health. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Psychiat & Behav Sci, Harborview Med Ctr, Seattle, WA 98104 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Vietnam Era Twin Registry, Seattle, WA USA. RP Roy-Byrne, PP (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Harborview Med Ctr, Seattle, WA 98104 USA. EM roybyrne@u.washington.edu FU NIAID NIH HHS [U19 AI038429-08, U19 AI038429]; NIAMS NIH HHS [R01 AR051524, R01 AR051524-02] NR 48 TC 4 Z9 4 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2006 VL 28 IS 5 BP 408 EP 413 DI 10.1016/j.genhosppsych.2006.05.007 PG 6 WC Psychiatry SC Psychiatry GA 086SO UT WOS:000240693500007 PM 16950376 ER PT J AU Bendig, G Grimmler, M Huttner, IG Wessels, G Dahme, T Just, S Trano, N Katus, HA Fishman, MC Rottbauer, W AF Bendig, Garnet Grimmler, Matthias Huttner, Inken G. Wessels, Georgia Dahme, Tillman Just, Steffen Trano, Nicole Katus, Hugo A. Fishman, Mark C. Rottbauer, Wolfgang TI Integrin-linked kinase, a novel component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart SO GENES & DEVELOPMENT LA English DT Article DE integrin-linked kinase (ILK); zebrafish; cardiac stretch sensor; beta-parvin (Affixin) ID GLYCOGEN-SYNTHASE KINASE; TUMOR-SUPPRESSOR PTEN; PROTEIN-KINASE; CELL-ADHESION; DILATED CARDIOMYOPATHY; PRESSURE-OVERLOAD; SIGNALING PATHWAY; EMBRYONIC HEART; FOCAL ADHESIONS; BETA-CATENIN AB The vertebrate heart possesses autoregulatory mechanisms enabling it first to sense and then to adapt its force of contraction to continually changing demands. The molecular components of the cardiac mechanical stretch sensor are mostly unknown but of immense medical importance, since dysfunction of this sensing machinery is suspected to be responsible for a significant proportion of human heart failure. In the hearts of the ethylnitros-urea (ENU)- induced, recessive embryonic lethal zebrafish heart failure mutant main squeeze (msq), we find stretch- responsive genes such as atrial natriuretic factor (anf) and vascular endothelial growth factor (vegf) severely down-regulated. We demonstrate through positional cloning that heart failure in msq mutants is due to a mutation in the integrin-linked kinase (ilk) gene. ILK specifically localizes to costameres and sarcomeric Z-discs. The msq mutation (L308P) reduces ILK kinase activity and disrupts binding of ILK to the Z- disc adaptor protein beta-parvin (Affixin). Accordingly, in msq mutant embryos, heart failure can be suppressed by expression of ILK, and also of a constitutively active form of Protein Kinase B (PKB), and VEGF. Furthermore, antisense- mediated abrogation of zebrafish beta-parvin phenocopies the msq phenotype. Thus, we provide evidence that the heart uses the Integrin-ILK-beta-parvin network to sense mechanical stretch and respond with increased expression of ANF and VEGF, the latter of which was recently shown to augment cardiac force by increasing the heart's calcium transients. C1 Univ Heidelberg, Dept Med 3, D-69120 Heidelberg, Germany. Univ Wurzburg, Bioctr, Dept Biochem, D-97074 Wurzburg, Germany. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Rottbauer, W (reprint author), Univ Heidelberg, Dept Med 3, D-69120 Heidelberg, Germany. EM wolfgang.rottbauer@med.uni-heidelberg.de RI Katus, Hugo/P-1712-2016 FU NHLBI NIH HHS [1R01HL63206, 5R01HL49579, R01 HL049579]; NIDDK NIH HHS [5R01DK55383] NR 50 TC 113 Z9 124 U1 0 U2 15 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 SEP 1 PY 2006 VL 20 IS 17 BP 2361 EP 2372 DI 10.1101/gad.1448306 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 081FU UT WOS:000240303400006 PM 16921028 ER PT J AU Takeda, S Chen, DY Westergard, TD Fisher, JK Rubens, JA Sasagawa, S Kan, JT Korsmeyer, SJ Cheng, EHY Hsieh, JJD AF Takeda, Shugaku Chen, David Y. Westergard, Todd D. Fisher, Jill K. Rubens, Jeffrey A. Sasagawa, Satoru Kan, Jason T. Korsmeyer, Stanley J. Cheng, Emily H. -Y. Hsieh, James J. -D. TI Proteolysis of MLL family proteins is essential for Taspase1-orchestrated cell cycle progression SO GENES & DEVELOPMENT LA English DT Article DE Taspase1; MLL; E2F; p16; cell cycle; cancer ID HISTONE METHYLTRANSFERASE COMPLEX; DROSOPHILA TRITHORAX GENE; PROTO-ONCOPROTEIN MLL; MAMMALIAN TRITHORAX; EXPRESSION; TFIIA; LEUKEMIA; E2F; TRANSCRIPTION; POLYCOMB AB Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper Hox gene expression in vitro. To investigate its functions in vivo, we generated Taspase1(-/-) mice. Taspase1 deficiency results in noncleavage (nc) of MLL and MLL2 and homeotic transformations. Remarkably, our in vivo studies uncover an unexpected role of Taspase1 in the cell cycle. Taspase1(-/-) animals are smaller in size. Taspase1(-/-) mouse embryonic fibroblasts ( MEFs) exhibit impaired proliferation, and acute deletion of Taspase1 leads to a marked reduction of thymocytes. Taspase1 deficiency incurs down- regulation of Cyclin Es, As, and Bs and up- regulation of p16(Ink4a). We show that MLL and MLL2 directly target E2Fs for Cyclin expression. The uncleaved precursor MLL displays a reduced histone H3 methyl transferase activity in vitro. Accordingly, chromatin immunoprecipitation assays demonstrate a markedly decreased histone H3 K4 trimethylation at Cyclin E1 and E2 genes in Taspase1(-/-) cells. Furthermore, MLLnc/nc;2nc/nc MEFs are also impaired in proliferation. Our data are consistent with a model in which precursor MILLs, activated by Taspase1, target to Cyclins through E2Fs to methylate histone H3 at K4, leading to activation. Lastly, Taspase1(-/-) cells are resistant to oncogenic transformation, and Taspase1 is overexpressed in many cancer cell lines. Thus, Taspase1 may serve as a target for cancer therapeutics. C1 Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Hsieh, JJD (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. EM jhsieh@im.wustl.edu FU NCI NIH HHS [CA R01-119008] NR 55 TC 88 Z9 91 U1 0 U2 1 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 SEP 1 PY 2006 VL 20 IS 17 BP 2397 EP 2409 DI 10.1101/gad.1449406 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 081FU UT WOS:000240303400009 PM 16951254 ER PT J AU Kay, DM Bird, TD Zabetian, CP Factor, SA Samii, A Higgins, DS Nutt, J Roberts, JW Griffith, A Leis, BC Montimurro, JS Philpott, S Payami, H AF Kay, Denise M. Bird, Tom D. Zabetian, Cyrus P. Factor, Stewart A. Samii, Ali Higgins, Donald S. Nutt, John Roberts, John W. Griffith, Alida Leis, Berta C. Montimurro, Jennifer S. Philpott, Sean Payami, Haydeh TI Validity and utility of a LRRK2 G2019S mutation test for the diagnosis of Parkinson's disease SO GENETIC TESTING LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM; NORTH-AFRICAN FAMILIES; EARLY-ONSET; CLINICAL-DIAGNOSIS; ALZHEIMER-DISEASE; COMMON FOUNDER; GENE; ACCURACY; ASSOCIATION; FREQUENCY AB The G2019S mutation in the LRRK2 gene, the most common known cause of Parkinson's disease (PD), will soon be widely available as a molecular clinical test for PD. The objective of this study was to assess performance characteristics of G2019S as a clinical test for PD in the setting of typical movement disorder clinics in the United States. Subjects included 1518 sequentially recruited PD patients from seven movement disorder clinics in the United States, and 1733 unaffected subjects. All 3251 subjects were genotyped for the G2019S mutation using a TaqMan assay, and mutations were verified by direct sequencing. Test validity estimates were calculated using standard methods. A total of 20/1518 patients and 1/1733 controls carried the G2019S mutation. Specificity was 99.9% (95% CI, 99.6-100%), sensitivity was 1.3% (0.8-2.1%), and the positive likelihood ratio was 22.8. A positive family history of PD increased the positive likelihood ratio to 82.5. Information on gender, age at disease onset, or age at testing did not improve test performance. The gene test was highly accurate in classifying mutation carriers as PD, but it performed poorly in predicting the phenotype of non-mutation carriers. A G2019S molecular test for PD would be highly specific, technically simple, and inexpensive. Test interpretation is straightforward when used for diagnosis of symptomatic individuals, but is more complex for risk assessment and predictive testing in asymptomatic individuals. Test results can have psychological, social, and economical ramifications; thus, proper counseling is essential. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. Univ Washington, Parkinsons Dis Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. Alden March Bioeth Inst, Albany, NY USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, POB 22002, Albany, NY 12201 USA. EM hpayami@wadsworth.org OI Kay, Denise/0000-0002-9928-2698 FU NIA NIH HHS [AG 08017, U24 AG021886]; NINDS NIH HHS [K08-NS044138, R01-NS36960] NR 42 TC 12 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD SEP PY 2006 VL 10 IS 3 BP 221 EP 227 DI 10.1089/gte.2006.10.221 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 094XI UT WOS:000241272100012 PM 17020475 ER PT J AU Eng, CM Germain, DP Banikazemi, M Warnock, DG Wanner, C Hopkin, RJ Bultas, J Lee, P Sims, K Brodie, SE Pastores, GM Strotmann, JM Wilcox, WR AF Eng, Christine M. Germain, Dominique P. Banikazemi, Maryam Warnock, David G. Wanner, Christoph Hopkin, Robert J. Bultas, Jan Lee, Philip Sims, Katherine Brodie, Scott E. Pastores, Gregory M. Strotmann, Joerg M. Wilcox, William R. TI Fabry disease: Guidelines for the evaluation and management of multi-organ system involvement SO GENETICS IN MEDICINE LA English DT Review DE agalsidase beta; enzyme replacement therapy; Fabry disease; alpha-galactosidase A; symptoms; treatment ID ENZYME-REPLACEMENT THERAPY; ALPHA-GALACTOSIDASE-A; ANGIOKERATOMA CORPORIS DIFFUSUM; ONSET HYPERTROPHIC CARDIOMYOPATHY; RETINAL ARTERY-OCCLUSION; CLINICAL-MANIFESTATIONS; PULMONARY INVOLVEMENT; NUCLEOTIDE-SEQUENCE; AGALSIDASE-ALPHA; NATURAL-HISTORY AB Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A, and the subsequent accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Males with classical Fabry disease develop early symptoms including pain and hypohidrosis by the second decade of life reflecting disease progression in the peripheral and autonomic nervous systems. An insidious cascade of disease processes ultimately results in severe renal, cardiac, and central nervous system complications in adulthood. The late complications are the main cause of late morbidity, as well as premature mortality. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic. The recent introduction of enzyme replacement therapy to address the underlying pathophysiology of Fabry disease has focused attention on the need for comprehensive, multidisciplinary evaluation and management of the multi-organ system involvement. In anticipation of evidence-based recommendations, an international panel of physicians with expertise in Fabry disease has proposed guidelines for the recognition, evaluation, and surveillance of disease-associated morbidities, as well as therapeutic strategies, including enzyme replacement and other adjunctive therapies, to optimize patient outcomes. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Hop Europeen Georges Pompidou, Paris, France. Mt Sinai Sch Med, New York, NY USA. Univ Alabama, Birmingham, AL USA. Univ Hosp, Dept Med, Wurzburg, Germany. Childrens Hosp, Cincinnati, OH 45229 USA. Charles Univ, Prague, Czech Republic. Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NYU, New York, NY USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Eng, CM (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza,NAB 2015, Houston, TX 77030 USA. OI Hopkin, Robert/0000-0003-0770-5516 NR 99 TC 189 Z9 211 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP PY 2006 VL 8 IS 9 BP 539 EP 548 DI 10.1097/01.gim.0000237866.70357.c6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 089YK UT WOS:000240917600001 PM 16980809 ER PT J AU Tepper, MC Dodes, LM Wool, CA Rosenblatt, LA AF Tepper, Miriam C. Dodes, Lance M. Wool, Carol A. Rosenblatt, Laurie A. TI A psychotherapy dominated by separation, termination, and death SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID DRUG-USE; ADDICTION; HEROIN; LOVE C1 Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cambridge Hlth Alliance, Boston, MA USA. Boston Psychoanalyt Inst & Soc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tepper, MC (reprint author), Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2006 VL 14 IS 5 BP 257 EP 267 DI 10.1080/10673220600975196 PG 11 WC Psychiatry SC Psychiatry GA 097DP UT WOS:000241427100004 PM 16990171 ER PT J AU Silvia, KA Sepucha, KR AF Silvia, Kerry A. Sepucha, Karen R. TI Decision aids in routine practice: lessons from the breast cancer initiative SO HEALTH EXPECTATIONS LA English DT Article DE clinical care; decision aids; early stage breast cancer; feasibility; implementation ID 20-YEAR FOLLOW-UP; MASTECTOMY; LUMPECTOMY; QUALITY; CHOICE; CARE AB Background Many decision aids have been developed to help patients make treatment and screening decisions; however, little is known about implementing them into routine clinical practice. Objective To assess the feasibility of implementing a patient decision aid (PtDA) for the early stage breast cancer surgical decision into routine clinical care. Design Structured individual interviews. Setting and participants A convenience sample of providers from nine sites, including two community resource centres, a community hospital and six academic centres. Main outcome measures Usage data, barriers to and resources for implementing the PtDAs. Results Six of the nine sites were using the PtDAs with patients. Two sites were primarily using a scheduling system and four sites relied on a lending system. For the academic centres, the keys to successful implementation included integrating the PtDA into the flow of patients through the centre and having physicians who recommended it to patients. At the community centres, the keys to successful implementation included an informed staff and the flexibility to get the PtDAs to patients in different ways. Barriers that limited or prevented sites from using the PtDA included a lack of clinical support, a lack of system support, competing priorities and scheduling problems. Conclusions It is feasible to implement a breast cancer PtDA into routine clinical care at academic centres and community resource centres. Future research should assess the effectiveness of PtDAs in routine clinical care as well as resources and barriers to their implementation in community hospitals. C1 Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. RP Sepucha, KR (reprint author), Massachusetts Gen Hosp, Hlth Decis Res Unit, 50 Staniford St,Suite 936, Boston, MA 02114 USA. EM ksepucha@partners.org NR 21 TC 24 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD SEP PY 2006 VL 9 IS 3 BP 255 EP 264 DI 10.1111/j.1369-7625.2006.00393.x PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 071XE UT WOS:000239636400007 PM 16911140 ER PT J AU Castelnuovo, E Thompson-Coon, J Pitt, M Cramp, M Siebert, U Price, A Stein, K AF Castelnuovo, E. Thompson-Coon, J. Pitt, M. Cramp, M. Siebert, U. Price, A. Stein, K. TI The cost-effectiveness of testing for hepatitis C in former injecting drug users SO HEALTH TECHNOLOGY ASSESSMENT LA English DT Review ID QUALITY-OF-LIFE; VIRUS-RELATED CIRRHOSIS; HEPATOCELLULAR-CARCINOMA DEVELOPMENT; LIVER FIBROSIS PROGRESSION; NATURAL-HISTORY; RISK-FACTORS; FOLLOW-UP; COMPENSATED CIRRHOSIS; DISEASE PROGRESSION; PROSPECTIVE COHORT AB Objectives: To evaluate the effectiveness and cost-effectiveness of testing for hepatitis C (HCV) among former injecting drug users (IDUs). Data sources: Electronic databases 1996-October 2004. Trent Regional Database Study. Routine UK mortality data. Review methods: A decision analytic model was developed to investigate the impact of case-finding and treatment on progression of HCV disease in a hypothetical cohort of 1000 people. This was compared with a cohort in whom no systematic case-finding is implemented but spontaneous presentation for testing is allowed to occur. A group of epidemiological and clinical experts informed the structure of the model, which has three main components: (1) testing and diagnosis, (2) treatment, and (3) long-term consequences of infection. A fourth component, case-finding strategies, examines the potential impact of case-finding in three settings: prisons, general practice and drug services. Results: Case-finding for HCV is likely to prevent, for 1000 people approached, three cases of decompensated cirrhosis, three deaths due to HCV and one case of hepatocellular cancer (at 30 years). Twenty-five additional people are likely to undergo combination therapy as a result of initial case-finding. One liver transplant is likely to be prevented for 10,000 people included in case-finding. Case-finding is likely to cost, in the general case, around 760,000 pound more than a policy of not case-finding. The total cost of either strategy is high and driven predominantly by the cost of treatment with combination therapy (the costs of long-term consequences are heavily discounted owing to the duration of the model). Systematically offering testing to 1000 people would cost around 70,000 pound. In terms of life-years gained, case-finding is likely to result in an additional life-year gained for an investment of 20,084 pound. Taking impacts on quality of life into account gives an estimate for the cost-utility of case-finding as 16,514 pound per QALY. The probabilistic sensitivity analysis shows that, if NHS policy makers view 30,000 pound per QALY as an acceptable return on investment, there is a 74% probability that case-finding for HCV would be considered cost-effective. At 20,000 pound per QALY, the probability that case-finding would be considered cost-effective is 64%. In all analyses, the probability of case-finding being considered cost-effective at a level of 30,000 pound per QALY was high. Case-finding in drug services is likely to be the most expensive, owing to the high prevalence of cases in the tested population. Correspondingly, benefits are highest for this strategy and cost-effectiveness is similar, in average terms, to the general case. Case-finding in general practice by offering testing to the whole population aged 30-54 years is, paradoxically, estimated to be the least expensive option as only a small number of people accept the offer of testing and HCV prevalence in this group is much higher than would be expected from the general population. Two approaches to case-finding in prison were considered, based on the results of studies in Dartmoor and the Isle of Wight prisons. These differed substantially in the prevalence of cases identified in the tested populations. The analysis based on data from Dartmoor prison had the least favourable average cost-effectiveness of the strategies considered (20,000 pound per QALY). Subgroup analyses based on duration of infection show that case-finding is likely to be most cost-effective in people whose infection is more long-standing and who are consequently at greater risk of progression. In people who were infected more than 20 years previously, case-finding yields benefits at around 15,000 pound per QALY. Treatment effectiveness was modelled using estimates from randomised controlled trials and lower rates of viral response may be seen in practice. However, estimates of cost-effectiveness remained below 30,000 pound for all levels of treatment effectiveness above 58% of those shown in the relevant trials. The value of information analysis, based on assumptions that 10,000 people might be eligible for case-finding and that programmes would run for 15 years, suggests that the maximum value of further research into case-finding is in excess of 19 pound million. Partial expected value of perfect information (EVPI) analysis shows that the utility estimates used in the model eclipse all other factors in terms of importance to parameter uncertainty. This is not surprising,since the point estimates for differences in utility between states and across the arms of the model are small. Conclusions: Case-finding for hepatitis C is likely to be considered cost-effective by NHS commissioners. Although there remains considerable uncertainty, it appears unlikely that cost-effectiveness would exceed the levels considered acceptable. Further improvements in the effectiveness of treatments to slow or halt disease progression are likely to improve the cost-effectiveness of case-finding. Case-finding is likely to be most cost-effective if targeted at people whose HCV disease is probably more advanced. Further empirical work is required to specify, in practice, different approaches to case-finding in appropriate settings and to evaluate their effectiveness and cost-effectiveness directly. C1 Univ Plymouth, Peninsular Med Sch, Peninsular Technol Assessment, Plymouth, Devon, England. Derriford Hosp, Plymouth PL6 8DH, Devon, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Southampton Hlth Technol Assessment Grp, Southampton, Hants, England. RP Stein, K (reprint author), Univ Exeter, Peninsular Med Sch, Peninsular Technol Assessment Grp, Exeter EX4 4QJ, Devon, England. NR 105 TC 48 Z9 48 U1 0 U2 1 PU GRAY PUBLISHING PI TUNBRIDGE WELLS PA RUSSELL HOUSE, GROVE HILL RD, TUNBRIDGE WELLS, TN1 1RZ, ENGLAND SN 1366-5278 J9 HEALTH TECHNOL ASSES JI Health Technol. Assess. PD SEP PY 2006 VL 10 IS 32 BP 1 EP + PG 88 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 087YP UT WOS:000240779000001 ER PT J AU Deaton, C Kimble, LP Veledar, E Hartigan, P Boden, WE O'Rourke, RA Weintraub, WS AF Deaton, Christi Kimble, Laura P. Veledar, Emir Hartigan, Pamela Boden, William E. O'Rourke, Robert A. Weintraub, William S. TI The synergistic effect of heart disease and diabetes on self-management, symptoms, and health status SO HEART & LUNG LA English DT Article ID CORONARY-ARTERY DISEASE; QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; CLINICAL-OUTCOMES; FUNCTIONAL STATUS; ANGINA-PECTORIS; MELLITUS; REVASCULARIZATION; IMPACT; BYPASS AB BACKGROUND: Coronary heart disease (CHD) and diabetes may have synergistic effects on symptoms, self-management, and general and cardiac-specific health status. PURPOSE: We compared symptom distress, self-management difficulties, and general and cardiac-specific health status in patients with CHD by the presence and severity of diabetes. METHODS: We performed a cross-sectional study of 1013 patients enrolled in the COURAGE trial, with the use of clinical data, the Symptom Distress Scale, the Self-Management Difficulties Scale, the Short-Form 36, and the Seattle Angina Questionnaire. RESULTS: Patients with diabetes and greater severity of diabetes had worse findings in symptom distress, self-management difficulties, and general and cardiac-specific health status than patients without diabetes. CONCLUSIONS: A robust effect of diabetes on symptom distress and self-management difficulties was found in patients with CHD. The results from the Seattle Angina Questionnaire illustrate difficulty in attributing physical limitations to specific symptoms or conditions, and show the experience of comorbid conditions to be synergistic. Clinicians' understanding of this synergy and integration of condition-specific care with general treatment and self-management practices are needed. C1 Univ Manchester, Sch Nursing Midwifery & Social Work, Manchester M13 9PL, Lancs, England. Emory Univ, Atlanta, GA 30322 USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, New Haven, CT USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Christiana Care Hlth Syst, Newark, DE USA. RP Deaton, C (reprint author), Univ Manchester, Sch Nursing Midwifery & Social Work, Coupland 3,Coupland St, Manchester M13 9PL, Lancs, England. RI Deaton, Christi/F-6485-2010; Veledar, Emir/K-2808-2012 OI Veledar, Emir/0000-0002-3831-5433 NR 26 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 EI 1527-3288 J9 HEART LUNG JI Heart Lung PD SEP-OCT PY 2006 VL 35 IS 5 BP 315 EP 323 DI 10.1016/j.hrting.2006.05.005 PG 9 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 085XO UT WOS:000240637900003 PM 16963363 ER PT J AU d'Avila, A Scanavacca, M Sosa, E AF d'Avila, Andre Scanavacca, Mauricio Sosa, Eduardo TI Transthoracic epicardial catheter ablation of ventricular tachycardia SO HEART RHYTHM LA English DT Editorial Material C1 Univ Sao Paulo, Sch Med, Heart Inst InCor, Cardiac Arrhythmia & Pacemaker Unit, Sao Paulo, Brazil. RP d'Avila, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre/A-7693-2009; Scanavacca, Mauricio Ibrahim/F-7693-2012; d'Avila, Andre Luiz/F-8009-2010 OI Scanavacca, Mauricio Ibrahim/0000-0001-7327-2275; d'Avila, Andre Luiz/0000-0001-8769-1411 NR 5 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD SEP PY 2006 VL 3 IS 9 BP 1110 EP 1111 DI 10.1016/j.hrthm.2006.03.029 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 085XI UT WOS:000240637300026 PM 16945813 ER PT J AU Albertson, RC Kocher, TD AF Albertson, R. C. Kocher, T. D. TI Genetic and developmental basis of cichlid trophic diversity SO HEREDITY LA English DT Review DE cichlid; adaptive radiation; jaw; bmp4; genetic architecture; cranial neural crest ID SMITH-MAGENIS-SYNDROME; NEURAL CREST CELLS; LAKE VICTORIA; FUNCTIONAL-MORPHOLOGY; EXPLOSIVE SPECIATION; SKELETAL DEVELOPMENT; TOOTH MORPHOGENESIS; FISHES TELEOSTEI; LABRID FISHES; ROSTRAL HEAD AB Cichlids have undergone extensive evolutionary modifications of their feeding apparatus, making them an ideal model to study the factors that underlie craniofacial diversity. Recent studies have provided critical insights into the molecular mechanisms that have contributed to the origin and maintenance of cichlid trophic diversity. We review this body of work, which shows that the cichlid jaw is regulated by a few genes of major additive effect, and is composed of modules that have evolved under strong divergent selection. Adaptive variation in cichlid jaw shape is evident early in development and is associated with allelic variation in and expression of bmp4. Modulating this growth factor in the experimentally tractable zebrafish model reproduces natural variation in cichlid jaw shape, supporting a role for bmp4 in craniofacial evolution. These data demonstrate the utility of the cichlid jaw as a model for studying the genetic and developmental basis of evolutionary changes in craniofacial morphology. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Univ New Hampshire, Hubbard Ctr Genome Studies, Durham, NH 03824 USA. RP Albertson, RC (reprint author), Syracuse Univ, Dept Biol, 130 Coll Pl, Syracuse, NY 13244 USA. EM CAlbertson@forsyth.org RI Kocher, Thomas/B-3089-2013; OI Kocher, Thomas/0000-0002-7547-0133 FU NIDCR NIH HHS [T32 DE08327] NR 87 TC 81 Z9 81 U1 12 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0018-067X J9 HEREDITY JI Heredity PD SEP PY 2006 VL 97 IS 3 BP 211 EP 221 DI 10.1038/sj.hdy.6800864 PG 11 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 077GC UT WOS:000240015900009 PM 16835594 ER PT J AU Kong, J White, NS Kwong, KK Vangel, MG Rosman, IS Gracely, RH Gollub, RL AF Kong, Jian White, Nathan S. Kwong, Kenneth K. Vangel, Mark G. Rosman, Ilana S. Gracely, Richard H. Gollub, Randy L. TI Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity SO HUMAN BRAIN MAPPING LA English DT Article DE cognitive; pain; fMRI; anterior insula; cingulate cortex ID ANTERIOR CINGULATE CORTEX; BRAIN ACTIVATION; RATIO SCALES; RESPONSES; STIMULATION; DESCRIPTORS; DIMENSION; HUMANS; LOBE AB Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, MGH MIT GCRC Biomed Imaging Core, Charlestown, MA 02129 USA. Univ Michigan, Hlth Syst, Dept Med Rheumatol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. Univ Michigan, Hlth Syst, Dept Neurol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. VAMC, Ann Arbor, MI USA. RP Kong, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Room 2661, Charlestown, MA 02129 USA. EM kongj@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU NCCIH NIH HHS [P01-AT002048-A-01, R21AT00949]; NIDA NIH HHS [R21 DA11229] NR 25 TC 125 Z9 128 U1 1 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2006 VL 27 IS 9 BP 715 EP 721 DI 10.1002/hbm.20213 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 074YZ UT WOS:000239849900002 PM 16342273 ER PT J AU DiMaio, SP Archip, N Hata, N Talos, IF Warfield, SK Majumdar, A McDannold, N Hynynen, K Morrison, PR Wells, WM Kacher, DF Ellis, RE Golby, AJ Black, PM Jolesz, FA Kikinis, R AF DiMaio, Simon P. Archip, Neculai Hata, Nobuhiko Talos, Ion-Florin Warfield, Simon K. Majumdar, Amit McDannold, Nathan Hynynen, Kullervo Morrison, Paul R. Wells, William M., III Kacher, Daniel F. Ellis, Randy E. Golby, Alexandra J. Black, Peter M. Jolesz, Ferenc A. Kikinis, Ron TI Image-guided neurosurgery at Brigham and Women's Hospital - The integration of imaging, navigation, and interventional devices SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID BRAIN SHIFT; GLIOBLASTOMA-MULTIFORME; CEREBRAL HEMISPHERE; ULTRASOUND SURGERY; DIFFUSION-TENSOR; RESECTION; EXTENT; MRI; SURVIVAL; GUIDANCE C1 Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Surg Planning Lab, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Radiol, Computat Radiol Lab, Boston, MA 02115 USA. MIT, Comp Sci & Artificial Lab, Cambridge, MA 02139 USA. Univ Calif San Diego, SCA Grp, SDSC, NSF Funded Supersompp & Computat Sci Res Ctr, La Jolla, CA 92093 USA. Brigham & Womens Hosp, Focused Ultrasound Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Magnet Resonance Imaging Div, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Brigham & Womens Canc Ctr, Brain Tumor Program, Boston, MA USA. Harvard Univ, Ctr Neurodegenerat & Repair, Cambridge, MA 02138 USA. ETH, Zurich, Switzerland. Univ Hosp, Zurich, Switzerland. RP DiMaio, SP (reprint author), Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, 75 Francis St, Boston, MA 02115 USA. EM simond@bwh.harvard.edu RI Warfield, Simon/B-3352-2009; Hata, Nobuhiko/L-5221-2014; OI Hata, Nobuhiko/0000-0002-6818-7700; Warfield, Simon/0000-0002-7659-3880 FU NCI NIH HHS [R25 CA089017, R25 CA89017-01]; NCRR NIH HHS [P41 RR013218, P41 RR019703, U41 RR019703, U41-RR019703]; NIBIB NIH HHS [U54 EB005149, U54-EB005149]; NIMH NIH HHS [R21 MH067054, R21 MH67054] NR 32 TC 21 Z9 21 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD SEP-OCT PY 2006 VL 25 IS 5 BP 67 EP 73 DI 10.1109/MEMB.2006.1705749 PG 7 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 086LJ UT WOS:000240674500014 PM 17020201 ER PT J AU Guellmar, D Haueisen, J Eiselt, M Giessler, F Flemming, L Anwander, A Knoesche, TR Wolters, CH Dumpelmann, M Tuch, DS Reichenbach, JR AF Guellmar, Daniel Haueisen, Jens Eiselt, Michael Giessler, Frank Flemming, Lars Anwander, Alfred Knoesche, Thomas R. Wolters, Carsten H. Duempelmann, Matthias Tuch, David S. Reichenbach, Juergen R. TI Influence of anisotropic conductivity on EEG source reconstruction: Investigations in a rabbit model SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE animal model; anisotropic conductivity; DTI; EEG; FEM; source localization ID SPREADING CORTICAL DEPRESSION; FINITE-ELEMENT ANALYSIS; TISSUE CONDUCTIVITY; SOURCE LOCALIZATION; INVERSE PROBLEM; MEG SIGNALS; HUMAN HEAD; BRAIN; PROPAGATION; IMPEDANCE AB The aim of our work was to quantify the influence of white matter anisotropic conductivity information on electroencephalogFaphy (EEG) source reconstruction. We performed this quantification in a rabbit head using both simulations and source localization based on invasive measurements. In vivo anisotropic (tensorial) conductivity information was obtained from magnetic resonance diffusion tensor imaging and included into a high-resolution finite-element model. When neglecting anisotropy in the simulations, we found a shift in source location of up to 1.3 min with a mean value of 0.3 mm. The averaged orientational deviation was 10 degree and the mean magnitude error of the dipole was 29 %. Source localization of the first cortical components after median and tibial nerve stimulation resulted in anatomically verified dipole positions with no significant anisotropy effect. Our results indicate that the expected average source localization error due to anisotropic white matter conductivity is within the principal accuracy limits of current inverse procedures. However, larger localization errors might occur in certain cases. In contrast, dipole orientation and dipole strength are influenced significantly by the anisotropy. We conclude that the inclusion of tissue anisotropy information improves source estimation procedures. C1 Inst Diagnost & Intervent Radiol, Biomagnet Ctr, Dept Neurol, D-07747 Jena, Germany. Inst Diagnost & Intervent Radiol, Biomagnet Ctr, Med Phys Grp, D-07747 Jena, Germany. FSU Jena, Inst Pathol Physiol, D-07747 Jena, Germany. Max Planck Inst Human Cognit & Brain Sci, D-04103 Leipzig, Germany. Univ Munster, Inst Biomagnet & Biosignalanalysis, D-48149 Munster, Germany. Eemagine Med Imaging Solut GmbH, D-12489 Berlin, Germany. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Guellmar, D (reprint author), Inst Diagnost & Intervent Radiol, Biomagnet Ctr, Dept Neurol, Erlanger Allee 101, D-07747 Jena, Germany. EM daniel.guellmar@med.uni-jena.de; jens.haueisen@tu-ilmenau.de; Michael.Eiselt@mti.uni-jena.de; giessler@biomag.uni-jena.de; anwander@cbs.mpg.de; knoesche@cbs.mpg.de; carsten.wolters@uni-muenster.de; Matthias.Duempelmann@eemagine.com; juergen.reichenbach@med.uni-jena.de RI Haueisen, Jens/B-7183-2011; Duempelmann, Matthias/K-2583-2012; Anwander, Alfred/B-5874-2011; Wolters, Carsten/R-4234-2016 OI Haueisen, Jens/0000-0003-3871-2890; Anwander, Alfred/0000-0002-4861-4808; Wolters, Carsten/0000-0001-6233-424X NR 41 TC 33 Z9 33 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD SEP PY 2006 VL 53 IS 9 BP 1841 EP 1850 DI 10.1109/TBME.2006.876641 PG 10 WC Engineering, Biomedical SC Engineering GA 076BW UT WOS:000239933000013 PM 16941840 ER PT J AU Peery, JT Klute, GK Blevins, JJ Ledoux, WR AF Peery, Jeffrey T. Klute, Glenn K. Blevins, Joanna J. Ledoux, William R. TI A three-dimensional finite element model of the transibial residual limb and prosthetic socket to predict skin temperatures SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE amputation; artificial limbs; biomechanics; heat transfer; prosthetics; rehabilitation ID TISSUE HEAT-TRANSFER; VASCULAR MICROSTRUCTURE; BIOHEAT EQUATION; SURFACE; FOUNDATION; FRICTION; GEOMETRY; BODY AB Amputees who wear prosthetic limbs often experience discomfort from blisters and sores due to mechanical insult; these skin conditions are exacerbated by elevated skin temperatures and excessive perspiration within the prosthetic socket. The goal of this study was to create a tool for developing new prostheses that accommodate varying thermal loads arising from everyday activities. A three-dimensional thermal model of a transtibial residual limb and prosthesis was constructed using the finite element (FE) method. Transverse computerized tomography (CT) scans were used to specify the geometry of the residual limb and socket. Thermal properties from the literature were assigned to both biological tissue and prosthetic socket elements. The purpose of this work was to create a model that would aid in testing the effect of new prosthesis designs on skin temperature. To validate its output, the model was used to predict the skin temperature distribution in a common prosthetic socket system (silicone liner, wool sock, and carbon fiber socket) at rest with no mechanical loading. Skin temperatures were generally elevated near muscle and decreased anteriorly and at the distal end. Experimental temperature measurements taken at the skin-prosthesis interface of five human subjects were used to validate the model. Data extracted from the thermal model at anterior, posterior, lateral, and medial locations were typically within one standard deviation of experimental results; the mean temperatures were within 0.3 degrees C for each section and were within 0.1 degrees C overall. C1 VA Puget Sound, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA 98108 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. RP Peery, JT (reprint author), VA Puget Sound, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA 98108 USA. EM jeffpeery@yahoo.com; gklute@u.washington.edu; jjb3@u.washington.edu; wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 25 TC 10 Z9 12 U1 2 U2 20 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD SEP PY 2006 VL 14 IS 3 BP 336 EP 343 DI 10.1109/TNSRE.2006.881532 PG 8 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 086UR UT WOS:000240699000010 PM 17009493 ER PT J AU Harris, JB Baresch-Bernal, A Rollins, SM Alam, A LaRocque, RC Bikowski, M Peppercorn, AF Handfield, M Hillman, JD Qadri, F Calderwood, SB Hohmann, E Breiman, RF Brooks, WA Ryan, ET AF Harris, Jason B. Baresch-Bernal, Andrea Rollins, Sean M. Alam, Ashfaqul LaRocque, Regina C. Bikowski, Margaret Peppercorn, Amanda F. Handfield, Martin Hillman, Jeffery D. Qadri, Firdausi Calderwood, Stephen B. Hohmann, Elizabeth Breiman, Robert F. Brooks, W. Abdullah Ryan, Edward T. TI Identification of in vivo-induced bacterial protein antigens during human infection with Salmonella enterica serovar Typhi SO INFECTION AND IMMUNITY LA English DT Article ID VIBRIO-CHOLERAE; TYPHIMURIUM VIRULENCE; TECHNOLOGY IVIAT; GENES; FEVER; MACROPHAGES; RESISTANCE; PHOP/PHOQ; VACCINE; GENOME AB We applied an immunoscreening technique, in vivo-induced antigen technology (IVIAT), to identify immunogenic bacterial proteins expressed during human infection with Salmonella enterica serovar Typhi, the cause of typhoid fever. We were able to assign a functional classification to 25 of 35 proteins identified by IVIAT. Of these 25, the majority represent proteins with known or potential roles in the pathogenesis of S. enterica. These include proteins implicated in fimbrial structure and biogenesis, antimicrobial resistance, heavy metal transport, bacterial adhesion, and extracytoplasmic substrate trafficking as well as secreted hydrolases. The 10 remaining antigens represent proteins with unknown functions. Of the 35 identified antigens, four had no immunoreactivity when probed with control sera from individuals never exposed to serovar Typhi organisms; these four included PagC, TcfB, and two antigens of unknown function encoded by STY0860 and STY3683. PagC is a virulence factor known to be upregulated in vivo in S. enterica serovar Typhimurium infection of mice. TcfB is the major structural subunit of a fimbrial operon found in serovar Typhi with no homolog in serovar Typhimurium organisms. By examining differential immunoreactivities in acute- versus convalescent-phase human serum samples, we found specific anti-PagC and anti-TcfB immunoglobulin G responses in patients with serovar Typhi bacteremia. Serovar Typhi antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis, and they may have diagnostic, therapeutic, or preventive uses. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. ICDDR B, Ctr Hlth & Populat Res, Dhaka, Bangladesh. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL USA. Oragenics, Alachua, FL USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jbharris@partners.org OI Rollins, Sean/0000-0002-3724-1989 FU FIC NIH HHS [K01 TW 07144, K01 TW 07409, K01 TW007144, K01 TW007409]; NIAID NIH HHS [U01 AI 58935, AI 40725, R01 AI040725, T32 AI 07061, T32 AI007061, U01 AI058935, U54 AI 057159, U54 AI057159]; NICHD NIH HHS [K12 HD 00850, K12 HD000850]; NIDCR NIH HHS [R01 DE 13523, R01 DE013523] NR 25 TC 47 Z9 57 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2006 VL 74 IS 9 BP 5161 EP 5168 DI 10.1128/IAI.00488-06 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 081DC UT WOS:000240296400022 PM 16926408 ER PT J AU Ouhara, K Komatsuzawa, H Shiba, H Uchida, Y Kawai, T Sayama, K Hashimoto, K Taubman, MA Kurihara, H Sugai, M AF Ouhara, Kazuhisa Komatsuzawa, Hitoshi Shiba, Hideki Uchida, Yushi Kawai, Toshihisa Sayama, Koji Hashimoto, Koji Taubman, Martin A. Kurihara, Hidemi Sugai, Motoyuki TI Actinobacillus actinomycetemcomitans outer membrane protein 100 triggers innate immunity and production of beta-defensin and the 18-kilodalton cationic antimicrobial protein through the fibronectin-integrin pathway in human gingival epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID NECROSIS-FACTOR-ALPHA; HUMAN BETA-DEFENSIN-2; STAPHYLOCOCCUS-AUREUS; PERIODONTAL-DISEASE; HUMAN KERATINOCYTES; ADAPTIVE IMMUNITY; SALIVARY-GLANDS; EXPRESSION; PEPTIDE; BINDING AB Antimicrobial peptides, human beta-defensin (hBD), and the 18-kDa cationic antimicrobial protein (CAP18) are components of innate immunity. These peptides have antimicrobial activity against bacteria, fungi, and viruses. Actinobacillus actinomycetemcomitans is a gram-negative facultative anaerobe implicated in the initiation of periodontitis. The innate immunity peptides have antibacterial activity against A. actinomycetemcomitans. We investigated the molecular mechanism of human gingival epithelial cells (HGEC) responding to exposure to A. actinomycetemcomitans. HGEC constitutively express hBD1 and inducibly express hBD2, hBD3, and CAP18 on exposure to A. actinomycetemcomitans. The level of expression varies among clinical isolates. In the signaling pathway for hBD2 induction by the bacterial contact, we demonstrate that the mitogen-activated protein (MAP) kinase and not the NF-kappa B transcription factor pathway is used. We found the outer membrane protein 100 (Omp100; identified by molecular mass) is the component inducing the hBD2 response. Omp100 binds to fibronectin, an extracellular matrix inducing hBD2 via the MAP kinase pathway. Anti-integrin alpha(5)beta(1), antifibronectin, genistein, and PP2 suppress the Omp100-induced expression of hBD2, suggesting that Src kinase is involved through integrin alpha(5)beta(1), The inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6 and IL-8, produced by HGEC on contact with A. actinomycetemcomitans also stimulate expression of hBD2. Further, neutralizing antibody against TNF-alpha or IL-8 partially inhibits the induction of hBD2 on bacterial contact. Therefore, we found that the induction of the antimicrobial peptides is mediated by a direct response principally through an Omp100-fibronectin interaction, and using secondary stimulation by inflammatory cytokines induced by the bacterial exposure. C1 Hiroshima Univ, Dept Bacteriol, Grad Sch Biomed Sci, Minami Ku, Hiroshima 7348553, Japan. Hiroshima Univ, Dept Periodontol Med, Grad Sch Biomed Sci, Hiroshima 7348553, Japan. Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Ehime Univ, Sch Med, Dept Dermatol, Shigenobu, Ehime 7910295, Japan. RP Komatsuzawa, H (reprint author), Hiroshima Univ, Dept Bacteriol, Grad Sch Biomed Sci, Minami Ku, Kasumi 1-2-3, Hiroshima 7348553, Japan. EM hkomatsu@hiroshima-u.ac.jp NR 67 TC 30 Z9 32 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2006 VL 74 IS 9 BP 5211 EP 5220 DI 10.1128/IAI.00056-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 081DC UT WOS:000240296400028 PM 16926414 ER PT J AU Patterson, JE AF Patterson, Jan E. TI Multidrug-resistant gram-negative pathogens: Multiple approaches and measures for prevention SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID INITIAL ANTIMICROBIAL THERAPY; BLOOD-STREAM INFECTIONS; SPECTRUM BETA-LACTAMASES; PSEUDOMONAS-AERUGINOSA; RISK-FACTORS; CLINICAL-OUTCOMES; MORTALITY; MICROBIOLOGY; BACTEREMIA; ORGANISMS C1 S Texas Vet Hlth Care Syst, Med Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Patterson, JE (reprint author), S Texas Vet Hlth Care Syst, Med Ctr, San Antonio, TX 78229 USA. EM pattersonj@uthscsa.edu NR 23 TC 9 Z9 9 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2006 VL 27 IS 9 BP 889 EP 892 DI 10.1086/507436 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 205AE UT WOS:000249084300001 PM 16941311 ER PT J AU Anstead, GM Graybill, JR AF Anstead, Gregory M. Graybill, John R. TI Coccidioidomycosis SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID CAVITARY PULMONARY COCCIDIOIDOMYCOSIS; AMPHOTERICIN-B; SURGICAL CONSIDERATIONS; TRANSPLANT RECIPIENTS; KETOCONAZOLE THERAPY; SEPTIC SHOCK; RISK-FACTORS; MENINGITIS; ITRACONAZOLE; IMMITIS AB Coccidioidomycosis is an infection caused by dimorphic fungi of the genus Coccidioides, soil-dwelling fungi endemic in semiarid to and life zones in the southwestern United States, northern Mexico, and scattered areas of Latin America. This article discusses populations at particular risk, diagnosis, clinical presentation, outcomes, and treatment of this potentially horrific disease. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, Res Serv, San Antonio, TX 78229 USA. RP Anstead, GM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM anstead@uthscsa.edu NR 111 TC 27 Z9 30 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 2006 VL 20 IS 3 BP 621 EP + DI 10.1016/j.idc.2006.06.005 PG 24 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 095JV UT WOS:000241304900008 PM 16984872 ER PT J AU Sherman, BJ Savage, CR Eddy, KT Blais, MA Deckersbach, T Jackson, SC Franko, DL Rauch, SL Herzog, DB AF Sherman, Bonnie J. Savage, Cary R. Eddy, Kamryn T. Blais, Mark A. Deckersbach, Thilo Jackson, Safia C. Franko, Debra L. Rauch, Scott L. Herzog, David B. TI Strategic memory in adults with anorexia nervosa: Are there similarities to obsessive compulsive spectrum disorders? SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE anorexia nervosa; obsessive-compulsive disorder; neuropsycological testing; memory; learning; Rey-Osterrieth Complex Figure Test (RCFT); strategic planning; cognition; organization ID BODY DYSMORPHIC DISORDER; POSITRON-EMISSION-TOMOGRAPHY; VERBAL-LEARNING STRATEGIES; BRAIN GLUCOSE-METABOLISM; EATING-DISORDERS; NONVERBAL MEMORY; BULIMIA-NERVOSA; NEUROPSYCHOLOGICAL IMPAIRMENT; ORGANIZATIONAL STRATEGIES; DIRECTED APPLICATION AB Objective: There is growing interest in the relationship between anorexia nervosa (AN) and obsessive-compulsive (OC) spectrum disorders (e.g., OCD, body clysmorphic disorder [EDD]). Previous neuropsychological investigations of OC spectrum disorders have identified problems with the efficient use of strategy on complex measures of learning and memory. This study evaluated nonverbal strategic memory in AN outpatients using an approach previously applied to OC spectrum disorders. Method: Eighteen patients with AN and 19 healthy control participants completed the Rey-Cisterrieth Complex Figure Test (RCFT), a widely used measure of nonverbal strategic planning, learning, and memory. Results: Individuals with AN differed significantly from healthy controls in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in learning were mediated by copy organizational strategies. Conclusion: These results are identical to study findings in OCD and BDD, indicating important shared neuropsychological features among AN and these OC spectrum disorders. As in OCD and 131313, the essential cognitive deficit in AN was impaired use of organizational strategies, which may inform our understanding of the pathophysiology of AN and potentially offer treatment implications. (c) 2006 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Boston Univ, Med Ctr, Ctr Excellence Womens Hlth, Boston, MA 02215 USA. Univ Kansas, Med Ctr, Dept Psychiat & Behav Sci, Kansas City, KS 66103 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. RP Herzog, DB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, YAW6900,55 Fruit St, Boston, MA 02114 USA. EM dherzog@partners.org OI Sherman, Bonnie/0000-0002-6322-8366 NR 54 TC 39 Z9 41 U1 4 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2006 VL 39 IS 6 BP 468 EP 476 DI 10.1002/eat.20300 PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 074HE UT WOS:000239802500005 PM 16715489 ER PT J AU Steinberg, M Corcoran, C Tschanz, J Huber, C Welsh-Bohmer, K Norton, MC Zandi, P Breitner, JCS Steffens, DC Lyketsos, CG AF Steinberg, M. Corcoran, C. Tschanz, J. T. Huber, C. Welsh-Bohmer, K. Norton, M. C. Zandi, P. Breitner, J. C. S. Steffens, D. C. Lyketsos, C. G. TI Risk factors for neuropsychiatric symptoms in dementia: The Cache County Study SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE dementia; neuropsychiatric; Alzheimer; risk factors ID ALZHEIMERS-DISEASE; BEHAVIORAL DISTURBANCES; PSYCHIATRIC-SYMPTOMS; MEDICAL COMORBIDITY; DELUSIONS; HALLUCINATIONS; IMPAIRMENT; PREVALENCE; PSYCHOSIS; INVENTORY AB Objective To investigate the probability of individual neuropsychiatric symptoms in dementia patients as a function of eight risk factors. Methods In the Cache County Study, we administered the Neuropsychiatric Inventory (NPI) to 328 dementia patients at baseline. Approximately 18 months later, we re-administered the NPI to 184 participants available for follow-up. Generalized estimating equation methods were used to model the probability of individual neuropsychiatric symptoms as a function of: gender, age, education, dementia type and severity, APOE status, time of observation, and general medical health. Results Women showed increased tendency toward anxiety, [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.313.76] and delusions (OR 2.15, Cl 1.22-3.78), but older persons of both sexes showed less tendency toward anxiety. Dementia severity increased the tendency toward hallucinations and agitation (OR 2.42, CI 1.81-3.23) and decreased risk of depression. Positive APOE epsilon 4 status increased the tendency toward aberrant motor behavior (OR 1.84, CI 1.05-3.22). Among dementia diagnoses, those with Alzheimer's disease showed decreased tendency toward agitation (OR 0.58, CI 0.350.95), depression (OR 0.56, CI 0.33-0.96) and disinhibition (OR 0.46, CI 0.24-0.88). Later time of observation increased risk of aberrant motor behavior and delusions, and more serious medical comorbidity increased risk of, agitation, irritability, disinhibition, and aberrant motor behavior. Conclusions Gender, age, dementia severity, APOE E4, dementia diagnosis, time of observation, and general medical health appear to influence the occurrence of individual neuropsychiatric symptoms. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Duke Univ, Dept Psychiat & Behav Sci, Sch Med, Durham, NC USA. Utah State Univ, Dept Family & Human Dev, Logan, UT 84322 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Washington, VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA. RP Steinberg, M (reprint author), Johns Hopkins Univ Hosp, 550 N Broadway,Suite 308, Baltimore, MD 21205 USA. EM martins@jhmi.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU NIA NIH HHS [AG-21136, AG-11380] NR 34 TC 33 Z9 35 U1 2 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD SEP PY 2006 VL 21 IS 9 BP 824 EP 830 DI 10.1002/gps.1567 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 091DV UT WOS:000241007400003 PM 16955439 ER PT J AU Ganis, G Kosslyn, SM AF Ganis, Giorgio Kosslyn, Stephen M. TI fMRI studies of different types of deception SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2006 VL 61 IS 3 SI SI BP 305 EP 306 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 071PT UT WOS:000239614800038 ER PT J AU Eisenstein, EM Eisenstein, D AF Eisenstein, E. M. Eisenstein, D. TI A behavioral homeostasis theory of habituation and sensitization from protozoa to humans SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 W Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2006 VL 61 IS 3 SI SI BP 318 EP 318 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 071PT UT WOS:000239614800085 ER PT J AU Steinhauer, SR Siegle, GJ Condray, R Gurklis, JA AF Steinhauer, Stuart R. Siegle, Greg J. Condray, Ruth Gurklis, John A., Jr. TI Pupil dilation during sustained processing: An indicator of intact effortful processing in schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2006 VL 61 IS 3 SI SI BP 338 EP 338 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 071PT UT WOS:000239614800152 ER PT J AU Chakravarti, A AF Chakravarti, Arnab TI Interpretation of molecular marker data in the modern era SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2006 VL 66 IS 1 BP 1 EP 2 DI 10.1016/j.ijrobp.2006.04.020 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 076BH UT WOS:000239931500001 PM 16904515 ER PT J AU Punglia, RS Weeks, JC Neville, BA Earle, CC AF Punglia, Rinaa S. Weeks, Jane C. Neville, Bridget A. Earle, Craig C. TI Effect of distance to radiation treatment facility on use of radiation therapy after mastectomy in elderly women SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation therapy; mastectomy; elderly; breast cancer; barriers to care ID BREAST-CONSERVING SURGERY; FEE-FOR-SERVICE; OLDER WOMEN; POSTOPERATIVE RADIOTHERAPY; ADJUVANT RADIOTHERAPY; PREMENOPAUSAL WOMEN; COMORBIDITY INDEX; CANCER PATIENTS; STAGE-I; CARCINOMA AB Purpose: We sought to study the effect of distance to the nearest radiation treatment facility on the use of postmastectomy radiation therapy (PMRT) in elderly women. Methods and Materials: Using data from the linked Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we analyzed 19,787 women with Stage I or II breast cancer who received mastectomy as definitive surgery during 1991 to 1999. Multivariable logistic regression was used to investigate the association of distance with receipt of PMRT after adjusting for clinical and sociodemographic factors. Results: Overall 2,075 patients (10.5%) treated with mastectomy received PMRT. In addition to cancer and patient characteristics, in our primary analysis, increasing distance to the nearest radiation treatment facility was independently associated with a decreased likelihood of receiving PMRT (OR = 0.996 per additional mile, p = 0.01). Secondary analyses revealed that the decline in PMRT use appeared at distances of more than 25 miles and was statistically significant for those patients living more than 75 miles from the nearest radiation facility (odds of receiving PMRT of 0.58 [95% CI = 0.34-0.99] vs. living within 25 miles of such a facility). The effect of distance on PMRT appeared to be more pronounced with increasing patient age (> 75 years). Variation in the effect of distance on radiation use between regions of the country and nodal status was also identified. Conclusions: Oncologists must be cognizant of the potential barrier to quality care that is posed by travel distance, especially for elderly patients; and policy makers should consider this fact in resource allocation decisions about radiation treatment centers. (c) 2006 Elsevier Inc. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Div Med Oncol, Boston, MA 02115 USA. RP Punglia, RS (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Radiat Oncol, 454B S21-24,44 Binney St, Boston, MA 02115 USA. EM rpunglia@lroc.harvard.edu NR 30 TC 46 Z9 46 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2006 VL 66 IS 1 BP 56 EP 63 DI 10.1016/j.ijrobp.2006.03.059 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 076BH UT WOS:000239931500009 PM 16814955 ER PT J AU Viswanathan, AN Cormack, R Holloway, CL Tanaka, C O'Farrell, D Devlin, PM Tempany, C AF Viswanathan, Akila N. Cormack, Robert Holloway, Caroline L. Tanaka, Cynthia O'Farrell, Desmond Devlin, Phillip M. Tempany, Clare TI Magnetic resonance-guided interstitial therapy for vaginal recurrence of endometrial cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Brachytherapy-Society CY JUN 01-03, 2005 CL San Francisco, CA SP Amer Brachytherapy Soc DE recurrent endometrial cancer; interstitial brachytherapy; magnetic resonance ID EXTERNAL-BEAM RADIOTHERAPY; GYNECOLOGIC MALIGNANCIES; CERVIX CANCER; INTRACAVITARY BRACHYTHERAPY; DEFINITIVE RADIOTHERAPY; SALVAGE RADIOTHERAPY; PROGNOSTIC FACTORS; RADIATION-THERAPY; HDR-BRACHYTHERAPY; CARCINOMA AB Purpose: To evaluate the feasibility and to describe the acute toxicity of a real-time intraoperative magnetic resonance (MR)-image guided interstitial approach to treating vaginal recurrence of endometrial cancer. Methods and Materials: From February 2004 to April 2005, 10 patients with recurrent endometrial cancer underwent MR-guided interstitial brachytherapy. Parameters evaluated included needle placement, dose-volume histograms (DVH), and complications. Results: Magnetic resonance-image guidance resulted in accurate needle placement. Tumor DVH values included median volume, 47 cc; V100, 89%; V150,61%; V200,38%; D90,71 Gy; and D100, 60 Gy. DVH of organs at risk resulted in a median D2cc of external beam and brachytherapy dose (% of brachytherapy prescription): bladder, 75Gy(3) (88%); rectum, 70Gy(3) (87%); and sigmoid, 56Gy(3) (41%). All patients experienced either a Grade 1 or 2 acute toxicity related to the radiation; only 1 patient had Grade 3 toxicity. No toxicities were attributable to the use of MR guidance. Conclusions: Real-time MR guidance during the insertion of interstitial needles reduces the likelihood of an inadvertent insertion of the needles into the bladder and the rectum. Three-dimensional dosimetry allows estimation of the dose to organs at risk. Toxicities are limited. (c) 2006 Elsevier Inc. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM aviswanathan@partners.org OI Cormack, Robert/0000-0001-5553-9984; Viswanathan, Akila/0000-0002-2003-0392 NR 59 TC 50 Z9 50 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2006 VL 66 IS 1 BP 91 EP 99 DI 10.1016/j.ijrobp.2006.04.037 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 076BH UT WOS:000239931500013 PM 16839709 ER PT J AU Weber, DC Miller, RC Villa, S Hanssens, P Baumert, BG Castadot, P Varlet, P Abacioglu, U Igdem, S Szutowicz, E Nishioka, H Hofer, S Rutz, HP Ozsahin, M Taghian, A Mirimanoff, RO AF Weber, Damien C. Miller, Robert C. Villa, Salvador Hanssens, Patrick Baumert, Brigitta G. Castadot, Pierre Varlet, Pascale Abacioglu, Ufuk Igdem, Sefik Szutowicz, Ewa Nishioka, Hiroshi Hofer, Silvia Rutz, Hans Peter Ozsahin, Mahmut Taghian, Alphonse Mirimanoff, Rene O. TI Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: A retrospective study from the rare cancer network SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE cerebellar glioblastoma; malignant glioma; posterior fossa tumors; radiotherapy; chemotherapy ID BRAIN-STEM GLIOMAS; HIGH-GRADE GLIOMAS; PHASE-II; TEMOZOLOMIDE; RADIOTHERAPY; IRRADIATION; RADIATION; INFRATENTORIAL; ASTROCYTOMAS; CHILDREN AB Purpose: The aim of this study was to assess the outcome in patients with cerebellar glioblastoma (GBM) treated in 15 institutions of the Rare Cancer Network. Methods and Materials: Data from a series of 45 adult patients with cerebellar GBM were collected in a retrospective multicenter study. Median age was 50.3 years. Brainstem invasion was observed in 9 (20%) patients. Radiotherapy (RT) was administered to 36 patients (with concomitant chemotherapy, 7 patients). Adjuvant chemotherapy after RT was administered in 8 patients. Median RT dose was 59.4 Gy. Median follow-up was 7.2 months (range, 3.4-39.0). Results: The 1-year and 2-year actuarial overall survival rate was 37.8% and 14.7%, respectively, and was significantly influenced by salvage treatment (p = 0.048), tumor volume (p = 0.044), extent of neurosurgical resection (p = 0.019), brainstem invasion (p = 0.0013), additional treatment after surgery (p < 0.001), and completion of the initial treatment (p < 0.001) on univariate analysis. All patients experienced local progression: 8 and 22 had progression with and without a distant failure, respectively. The 1- and 2-year actuarial progression free survival was 25% and 10.7%, respectively, and was significantly influenced by brainstem invasion (p = 0.002), additional treatment after surgery (p = 0.0016), and completion of the initial treatment (p < 0.001). On multivariate analysis, survival was negatively influenced by the extent of surgery (p = 0.03) and brainstem invasion (p = 0.02). Conclusions: In this multicenter retrospective study, the observed pattern of failure was local in all cases, but approximately 1 patient of 4 presented with an extracerebellar component. Brainstem invasion was observed in a substantial number of patients and was an adverse prognostic factor. (c) 2006 Elsevier Inc. C1 Univ Hosp Geneva, Dept Radiat Oncol, CH-1211 Geneva 14, Switzerland. Mayo Clin, Rochester, MI USA. Inst Catala Oncol, Barcelona, Spain. Dr Bernard Verbeeten Inst, Tilburg, Netherlands. Univ Hosp, Dept Radiat Therapy, MAASTRO Clin, GROW, Maastricht, Netherlands. Inst Jules Bordet, B-1000 Brussels, Belgium. Ctr Hosp St Anne, Paris, France. Marmara Univ Hosp, Istanbul, Turkey. Metropolitan Hosp, Istanbul, Turkey. Med Univ Gdansk, Gdansk, Poland. Tokyo Med Univ, Dept Neurosurg, Tokyo, Japan. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Paul Scherrer Inst, Villigen, Switzerland. CHU Vaudois, CH-1011 Lausanne, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weber, DC (reprint author), Univ Hosp Geneva, Dept Radiat Oncol, CH-1211 Geneva 14, Switzerland. EM damien.weber@hcuge.ch OI Abacioglu, Ufuk/0000-0002-3950-8616 NR 41 TC 24 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2006 VL 66 IS 1 BP 179 EP 186 DI 10.1016/j.ijrobp.2006.04.035 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 076BH UT WOS:000239931500023 PM 16814953 ER PT J AU Rietzel, E Liu, AK Doppke, KP Wolfgang, JA Chen, AB Chen, GTY Choi, NC AF Rietzel, Eike Liu, Arthur K. Doppke, Karen P. Wolfgang, John A. Chen, Aileen B. Chen, George T. Y. Choi, Noah C. TI Design of 4D treatment planning target volumes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE four-dimensional computed tomography; four-dimensional treatment planning; treatment planning; target volumes; organ motion ID LUNG-TUMOR MOTION; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; MULTIPLE CT SCANS; RESPIRATORY MOTION; ORGAN MOTION; CANCER; ARTIFACTS; MOVEMENT; MOBILITY AB Purpose: When using non-patient-specific treatment planning margins, respiratory motion may lead to geometric miss of the target while unnecessarily irradiating normal tissue. Imaging different respiratory states of a patient allows patient-specific target design. We used four-dimensional computed tomography (4DCT) to characterize tumor motion and create treatment volumes in 10 patients with lung cancer. These were compared with standard treatment volumes. Methods and Materials: Four-dimensional CT and free breathing helical CT data of 10 patients were acquired. Gross target volumes (GTV) were delineated on the helical scan as well as on each phase of the 4D data. Composite GTVs were defined on 4DCT. Planning target volumes (PTV) including clinical target volume, internal margin (IM), and setup margin were generated. 4DPTVs with different IMs and standard PTVs were compared by computing centroid positions, volumes, volumetric overlap, and bounding boxes. Results: Four-dimensional PTVs and conventional PTVs differed in volume and centroid positions. Overlap between 4DPTVs generated from two extreme tumor positions only compared with 10 respiratory phases was 93.7%. Comparing PTVs with margins of 15 mm (IM 5 mm) on composite 4D target volumes to PTVs with 20 mm (IM 10 mm) on helical CT data resulted in a decrease in target volume sizes by 23% on average. Conclusion: With patient-specific characterization of tumor motion, it should be possible to decrease internal margins. Patient-specific treatment volumes can be generated using extreme tumor positions on 4DCT. To date, more than 150 patients have been treated using 4D target design. (c) 2006 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NE Proton Therapy Ctr,Dept Radiat Oncol, Boston, MA 02114 USA. Gesell Schwerionenforsch mbH, Biophys Abt, Darmstadt, Germany. RP Rietzel, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NE Proton Therapy Ctr,Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM eike@rietzel.net OI Chen, Aileen/0000-0002-5385-3360 FU NCI NIH HHS [P01-CA21239] NR 39 TC 107 Z9 127 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2006 VL 66 IS 1 BP 287 EP 295 DI 10.1016/j.ijrobp.2006.05.024 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 076BH UT WOS:000239931500039 PM 16904528 ER PT J AU Velmahos, GC Gkiokas, G Chan, LS Brown, CV Salim, A Rhee, P Demetriades, D AF Velmahos, George C. Gkiokas, George Chan, Linda S. Brown, Carlos V. Salim, Ali Rhee, Peter Demetriades, Demetrios TI Nephrectomy versus renal repair after trauma to the kidney: Preserve or sacrifice? SO INTERNATIONAL SURGERY LA English DT Article DE nephrectomy; nephrorrhaphy; renal injury; kidney; renal repair; renal failure; renal dialysis ID GUNSHOT WOUNDS; CONSERVATIVE MANAGEMENT; NONOPERATIVE MANAGEMENT; UNILATERAL NEPHRECTOMY; VASCULAR CONTROL; URINARY-TRACT; INJURIES; BLUNT; RECONSTRUCTION; LACERATIONS AB The objective of this retrospective study (1992-2003) is to evaluate the effect of nephrectomy in postoperative renal dysfunction. NEPHRECTOMY patients had their kidneys removed and REPAIR patients repaired or only partially resected. All patients were matched 1:1 with controls according to age, Injury Severity Score, Abdominal Abbreviated Injury Score, and mechanism of injury. Outcomes measured were renal dysfunction (serum creatinine > 2 mg/dl for > 2 consecutive days), renal dialysis, length of hospital stay, and mortality. Of 214 patients, 149 were NEPHRECTOMY and 65 REPAIR. Compared to their controls, NEPHRECTOMY and REPAIR patients had a higher rate of renal dysfunction. However, the rate was not different between NEPHRECTOMY and REPAIR. Multivariate analysis found no independent effect of the choice of operation in the development of renal dysfunction. No differences were found in the remaining outcomes measured. We conclude that although renal injury is associated with postoperative renal dysfunction, the type of operation is not. Nephrectomy can be offered when necessary without concerns about increasing the likelihood of postoperative renal failure. C1 Univ So Calif, Dept Surg, Div Trauma & Crit Care, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biostat & Outcomes Res, Los Angeles, CA 90089 USA. Los Angeles Cty & Univ So Calif, Med Ctr, Los Angeles, CA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org RI International Surgery, ICS/D-3993-2011 NR 29 TC 1 Z9 1 U1 0 U2 0 PU INT COLLEGE OF SURGEONS PI CHICAGO PA 1516 N LAKE SHORE DR, CHICAGO, IL 60610 USA SN 0020-8868 J9 INT SURG JI Int. Surg. PD SEP-OCT PY 2006 VL 91 IS 5 BP 295 EP 300 PG 6 WC Surgery SC Surgery GA 091DP UT WOS:000241006800011 PM 17061677 ER PT J AU Jhawer, M Mani, S Lefkopoulou, M Hahn, RG Harris, J Catalano, PJ Haller, D AF Jhawer, M Mani, S Lefkopoulou, M Hahn, RG Harris, J Catalano, PJ Haller, D TI Phase II study of mitomycin-C, adriamycin, cisplatin (MAP) and Bleomycin-CCNU in patients with advanced cancer of the anal canal: An eastern cooperative oncology group study E7282 SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE anal cancer; mitomycin-C; adriamycin; cisplatin; bleomycin; CCNU; phase II ID SQUAMOUS-CELL CARCINOMA; RANDOMIZED-TRIAL; PLEURAL MESOTHELIOMA; DOXORUBICIN; COMBINATION; CHEMOTHERAPY; ANUS; MANAGEMENT; CERVIX AB Metastatic anal cancer is a rare disease in the Western hemisphere and current treatment modalities are not effective. In this study, patients with advanced epithelial cancer of the anal canal received MAP followed by Bleomycin and CCNU upon progression of disease. Twelve out of twenty eligible patients had a partial response 60%, (95% CI {36% -81%}). No complete responses were observed. The median survival was 15 months (95% CI {6-20} months). The median time to progression or death was 8 months (95% CI {4-9 months}). Toxicities were moderate and tolerable with routine supportive care; there were 2 cases of grade 3 vomiting, 2 cases of respiratory distress (one grade 1 and one grade 3), one case each of grade 3 leg cramps and cardiac arrhythmia. Of particular note were 7 cases of grade 3 hematologic toxicity. Two patients had grade 4 leukopenia and thrombocytopenia, respectively, that resolved without sequelae. The combination therapy of MAP followed by Bleomycin and CCNU for patients with advanced anal cancer, not amenable to radiotherapy or surgery, results in a moderate objective response but with moderate toxicities. This regimen and sequence is worthy of further study especially in combination with colony stimulating factors, however, its tolerability may be most applicable for patients who have had minimal prior therapy. C1 Jack D Weiler Hosp, Dept Oncol, Montefiore Med Ctr, Bronx, NY 10461 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. RP Mani, S (reprint author), Jack D Weiler Hosp, Dept Oncol, Montefiore Med Ctr, Room 2S-49,1825 Eastchester Rd, Bronx, NY 10461 USA. EM smani@montefiore.org FU NCI NIH HHS [CA15488, CA 66636, CA13650, CA14958, CA21115, CA23318, CA25988] NR 23 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD SEP PY 2006 VL 24 IS 5 BP 447 EP 454 DI 10.1007/s10637-006-7667-x PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 051HC UT WOS:000238151200011 PM 16763788 ER PT J AU Oh, DJ Martin, JL Williams, AJ Russell, P Birk, DE Rhee, DJ AF Oh, Dong-Jin Martin, Jonathan L. Williams, Adrienne J. Russell, Paul Birk, David E. Rhee, Douglas J. TI Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AQUEOUS-HUMOR DYNAMICS; CYNOMOLGUS MONKEY EYES; SMOOTH-MUSCLE-CELLS; INTRAOCULAR-PRESSURE; EXTRACELLULAR-MATRIX; OCULAR HYPERTENSION; CATALYTIC DOMAIN; PROGELATINASE-A; GENE-EXPRESSION; CILIARY MUSCLE AB PURPOSE. To determine the effect of latanoprost on the expression of human matrix metalloproteinases ( MMPs) and tissue inhibitors of metalloproteinases ( TIMPs) in the trabecular meshwork ( TM). METHODS. Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human TM tissue and explant cultures of TM endothelial cells. Cultures of TM cells were treated with vehicle control or latanoprost acid for 24 hours. Real-time RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS. The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 and of TIMP-1 to -4 was present in TM tissue and cultures of TM cells. MMP-9 was not found. In control TM endothelial cells, the relative expression of MMP mRNA were MMP-2 and -14 > MMP-16, -19, and -24 > MMP-15 > MMP-11 and -17 > MMP-1 and -3 > MMP-12. The relative expressions of TIMP mRNA were TIMP-1 > TIMP-2 and -3 > TIMP-4. Latanoprost increased MMP-1 ( in four of five cultures), MMP-3 ( in four of five cultures), MMP-17 ( in three of five cultures), MMP-24 ( in all five cultures), TIMP-2, -3, and -4 expression ( in three of five cultures); MMP-11 and -15 were downregulated. CONCLUSIONS. Contrary to the expected result, latanoprost seems to have a significant effect on TM cells. The transcription of the genes for MMP-1, -3, -17, and -24 is increased by latanoprost treatment. TIMP-2, -3, and -4 are also upregulated. The upregulation of these TIMPs may compensate for the increase of those MMPs. The absence of MMP-9 and concurrent upregulation of a greater number of TIMPs may explain the limited effect of latanoprost on TM outflow. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Thomas Jefferson Univ, Wills Eye Hosp, Lab Mol Ophthalmol, Philadelphia, PA 19107 USA. NEI, Sect Aging & Ocular Dis, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com RI Birk, David/I-4072-2012 OI Birk, David/0000-0002-4865-9088 FU NEI NIH HHS [EY 13997] NR 64 TC 42 Z9 42 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2006 VL 47 IS 9 BP 3887 EP 3895 DI 10.1167/iovs.06-0036 PG 9 WC Ophthalmology SC Ophthalmology GA 077SP UT WOS:000240050700028 PM 16936101 ER PT J AU Zamiri, P Masli, S Streilein, JW Taylor, AW AF Zamiri, Parisa Masli, Sharmila Streilein, J. Wayne Taylor, Andrew W. TI Pigment epithelial growth factor suppresses inflammation by modulating macrophage activation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; EPIDERMAL LANGERHANS CELLS; NITRIC-OXIDE; IMMUNE PRIVILEGE; NEUROTROPHIC FACTOR; AQUEOUS-HUMOR; TGF-BETA; T-CELLS; ANGIOGENESIS; PEDF AB PURPOSE. To study the contribution of murine retinal pigment epithelial (RPE) cells to the innate immune-privilege status of the subretinal space as determined by the ability of pigment epithelial-derived factor ( PEDF) and somatostatin (SOM), produced by RPE, to regulate macrophage-mediated inflammation. METHODS. Serum-free medium was added to RPE eyecups ( a healthy monolayer of RPE resting on choroid and sclera) and the supernatants were removed after 24 hours ( RPE SN). The RPE SN was assayed for the presence of PEDF and SOM and for its ability to regulate interleukin (IL)-12, IL-10, and nitric oxide ( NO) production by resting and activated macrophages. A group of mice received intradermal injection of lipopolysaccharide (LPS) and PEDF in one ear and LPS alone in the other ear. Ear thickness was measured before- and 24 hours after ear injections. RESULTS. Soluble factors present in the RPE SN inhibited IL-12 production and substantially increased IL-10 while having minimal effects on NO production by activated macrophages. The message for PEDF, SOM, and IL-10 was detected in RPE cells, and the protein for these factors was found in the RPE SN. The stimulation of IL-10 and suppression of IL-12 production by RPE-SN-treated macrophages was neutralized by anti-PEDF antibodies. Neutralization of SOM in the RPE SN, suppressed NO production by activated macrophages. Intradermal injection of PEDF substantially inhibited LPS-induced inflammatory response. CONCLUSIONS. PEDF inhibits LPS-driven macrophage activation in vitro and in vivo. By producing PEDF, the RPE contributes to innate immune privilege of the eye. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. RP Zamiri, P (reprint author), Wellman Ctr Photomed, Dept Adv Microscopy, Bartlett Extens 630,55 Fruit St, Boston, MA 02114 USA. EM pzamiri@partners.org OI Taylor, Andrew/0000-0002-0330-8591 FU NEI NIH HHS [EY05678, R01 EY010752, R01 EY010752-10, R01 EY015472] NR 41 TC 68 Z9 70 U1 1 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2006 VL 47 IS 9 BP 3912 EP 3918 DI 10.1167/iovs.05-1267 PG 7 WC Ophthalmology SC Ophthalmology GA 077SP UT WOS:000240050700031 PM 16936104 ER PT J AU Liberman, MC Tartaglini, E Fleming, JC Neufeld, EJ AF Liberman, M. C. Tartaglini, E. Fleming, J. C. Neufeld, E. J. TI Deletion of SLC19A2, the high affinity thiamine transporter, causes selective inner hair cell loss and an auditory neuropathy phenotype SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE sensorineural hearing loss; thiamine responsive megaloblastic anemia ID CARBOPLATIN-TREATED CHINCHILLAS; DIABETES-MELLITUS; DEAFNESS; ANEMIA; CISPLATIN; MUTATIONS; COCHLEA; MICE AB Mutations in the gene coding for the high-affinity thiamine transporter Slc19a2 underlie the clinical syndrome known as thiamine-responsive megaloblastic anemia (TRMA) characterized by anemia, diabetes, and sensorineural hearing loss. To create a mouse model of this disease, a mutant line was created with targeted disruption of the gene. Cochlear function is normal in these mutants when maintained on a high-thiamine diet. When challenged with a low-thiamine diet, Slc19a2-null mice showed 40-60 dB threshold elevations by auditory brainstem response (ABR), but only 10-20 dB elevation by otoacoustic emission (OAE) measures. Wild-type mice retain normal hearing on either diet. Cochlear histological analysis showed a pattern uncommon for sensorineural hearing loss: selective loss of inner hair cells after 1-2 weeks on low thiamine and significantly, greater inner than outer hair cell loss after longer low-thiamine challenges. Such a pattern is consistent with the observed discrepancy between ABR and OAE threshold shifts. The possible role of thiamine transport in other reported cases of selective inner hair cell loss is considered. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Childrens Hosp, Div Hematol, Boston, MA 02115 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM charles_liberman@meei.harvard.edu RI Neufeld, Ellis/F-9331-2011 FU NIDCD NIH HHS [P30 DC005209, P30 DC05209, R01 DC 04820, R01 DC000188, R01 DC004820] NR 21 TC 38 Z9 45 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD SEP PY 2006 VL 7 IS 3 BP 211 EP 217 DI 10.1007/s10162-006-0035-x PG 7 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 078YS UT WOS:000240143300002 PM 16642288 ER PT J AU Pumbwe, L Chang, A Smith, RL Wexler, HM AF Pumbwe, Lilian Chang, Abraham Smith, Rachel L. Wexler, Hannah M. TI Clinical significance of overexpression of multiple RND-family efflux pumps in Bacteroides fragilis isolates SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE cross-resistance; therapy; susceptibility ID RESISTANT PSEUDOMONAS-AERUGINOSA; II TOPOISOMERASE MUTATIONS; EXTENSIVE DNA INVERSIONS; FLUOROQUINOLONE RESISTANCE; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; QUINOLONE RESISTANCE; ANAEROBIC-BACTERIA; GENE-EXPRESSION; BETA-LACTAMASE AB Objectives: The aim of the present study was to determine correlation between bmeB efflux pump overexpression and resistance to fluoroquinolones and beta-lactams in Bacteroides fragilis clinical isolates (n = 51) and the effects of broad-spectrum efflux pump inhibitors (EPIs) on the MICs of the test antibiotics. Methods: Susceptibility to garenoxacin, levofloxacin, moxifloxacin, cefoxitin and faropenem +/- EPIs (CCCP, MC-207,110, reserpine and verapamil) was determined. Expression of bmeB efflux pumps was measured, topoisomerase genes were sequenced and beta-lactamase production was determined. Results: Isolates were grouped into categories based on susceptibility patterns, topoisomerase sequence and efflux pump expression. Panel I isolates (19/51, 37.3%) were highly resistant to fluoroquinolones and cefoxitin (resistance to all agents was significantly reduced by EPIs, P < 0.05), had a point mutation in gyrA (C -> T) causing a Ser-82 -> Phe substitution, and overexpressed bmeB4 and bmeB15. Panel II isolates (7/51; 13.7%) had intermediate-level resistance to fluoroquinolones and cefoxitin and a GyrA substitution. Panel IIIA isolates (21/51; 41.2%) had intermediate-level fluoroquinolone resistance and high-level cefoxitin resistance [resistance to all agents was significantly reduced by EPIs (P < 0.05)] and overexpressed bmeB4 and bmeB15. Panel IIIB isolates (4/51; 7.8%) had low-level fluoroquinolone resistance and high-level resistance to cefoxitin [cefoxitin resistance was significantly reduced by EPIs (P < 0.05)] and overexpressed bmeB4, bmeB6, bmeB10 and bmeB14. All isolates were beta-lactamase-positive. Conclusions: These data suggest that bmeB efflux pump overexpression can (i) cause low- to intermediate-level clinically relevant fluoroquinolone resistance; (ii) be coupled with GyrA substitutions to cause high-level fluoroquinolone resistance; (iii) contribute to high-level clinically relevant resistance to beta-lactams. C1 Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Wexler, HM (reprint author), Greater Los Angeles Vet Adm Healthcare Syst, 691-151J,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hwexler@ucla.edu NR 35 TC 21 Z9 24 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD SEP PY 2006 VL 58 IS 3 BP 543 EP 548 DI 10.1093/jac/dkl278 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 075RI UT WOS:000239902500010 PM 16840432 ER PT J AU Kaka, AS Rueda, AM Shelburne, SA Hulten, K Hamill, RJ Musher, DM AF Kaka, Anjum S. Rueda, Adriana M. Shelburne, Samuel A., III Hulten, Kristina Hamill, Richard J. Musher, Daniel M. TI Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE trimethoprim; sulfamethoxazole; linezolid; time-kill; bactrim ID TRIMETHOPRIM-SULFAMETHOXAZOLE; INFECTIONS; VANCOMYCIN AB Background: The recent proliferation of community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) has led to a marked increase in the need for outpatient treatment of MRSA infections. Many oral agents active against MRSA have been available for years, and a paucity of literature compares them, leaving physicians with little guidance for choosing among them. The purpose of the present study was to compare the bactericidal effects of orally available antibiotics against MRSA and to determine whether there were differences in antimicrobial killing activity against CA-MRSA and hospital-acquired (HA) MRSA isolates. Methods: A total of 12 unique patient MRSA isolates were studied. Six strains were CA, carrying the staphylococcal chromosomal cassette (SCCmec) type IVa, while six were HA and carried SCCmec type II. Time-kill methods were used to study the bactericidal activity of the orally available antimicrobials linezolid, rifampicin, trimethoprim/sulfamethoxazole, clindamycin, minocycline, and moxifloxacin alone and in combination in vitro. Results: Trimethoprim/sulfamethoxazole was rapidly bactericidal resulting in > 2 log(10) cfu/mL decrease at 8 h and > 3 log(10) cfu/mL decrease at 24 h in vitro. No antibiotic combination exhibited better killing than trimethoprim/sulfamethoxazole alone. Adding rifampicin to trimethoprim/sulfamethoxazole showed a trend towards antagonism in vitro. There were no differences in the bactericidal activity of any antimicrobial or antimicrobial combination against MRSA isolates carrying SCCmec type IVa versus those carrying SCCmec type II. Conclusion: Trimethoprim/sulfamethoxazole is rapidly bactericidal against MRSA in vitro when compared with most other orally available antimicrobials. No differences in bactericidal activity were detected when activities against CA-MRSA and HA-MRSA were compared. C1 Michael E DeBakey Vet Affairs Med Ctr, Sect Infect Dis 111G, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Infect Dis Sect, Houston, TX 77030 USA. RP Musher, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Sect Infect Dis 111G, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Daniel.Musher@va.gov OI Hulten, Kristina/0000-0001-7446-157X FU NCRR NIH HHS [K12 RR 1766504]; NIAID NIH HHS [5T32AI055413-03] NR 10 TC 61 Z9 62 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD SEP PY 2006 VL 58 IS 3 BP 680 EP 683 DI 10.1093/jac/dkl283 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 075RI UT WOS:000239902500033 PM 16840428 ER PT J AU Bozic, KJ Wagie, A Naessens, JM Berry, DJ Rubash, HE AF Bozic, Kevin J. Wagie, Amy Naessens, James M. Berry, Daniel J. Rubash, Harry E. TI Predictors of discharge to an inpatient extended care facility after total hip or knee arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Association-of-Hip-and-Knee-Surgeons CY NOV 04-06, 2005 CL Dallas, TX SP Amer Assoc Hip & Knee Surg DE total joint arthroplasty; discharge planning; postactite care; outcomes AB Increased emphasis has been placed on hospital length of stay and discharge planning after total joint arthroplasty (TJA). The purpose of this study was to identify baseline patient characteristics that are predictive of discharge to all inpatient extended care facility (ECF) after TJA. Clinical, demographic, and resource utilization data were analyzed for 7818 consecutive patients who underwent primary or revision TJA at 1 of 3 high-volume TJA centers. A stepwise linear regression model was used to identify predictors of discharge to an ECF. Overall, 29% of patients were discharged to an ECF after TJA. Older age, higher American Society of Anesthesiologists class, Medicare insurance, and female sex were all associated with a higher likelihood of discharge to an ECF. Significant differences in practice patterns were found across hospitals with respect to discharge disposition after TJA. Further study is necessary to determine the appropriate criteria for discharge to an ECF after TJA. C1 Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. NR 15 TC 36 Z9 36 U1 0 U2 4 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 2006 VL 21 IS 6 SU 2 BP 151 EP 156 DI 10.1016/j.arth.2006.04.015 PG 6 WC Orthopedics SC Orthopedics GA 086QS UT WOS:000240688700026 PM 16950078 ER PT J AU Alper, CA Husain, Z Larsen, CE Dubey, DP Stein, R Day, C Baker, A Beyan, H Hawa, M Ola, TO Leslie, RD AF Alper, Chester A. Husain, Zaheed Larsen, Charles E. Dubey, Devendra P. Stein, Rosanne Day, Caitlin Baker, Alissa Beyan, Huriya Hawa, Mohammed Ola, Thomas O. Leslie, R. David TI Incomplete penetrance of susceptibility genes for MHC-determined immunoglobulin deficiencies in monozygotic twins discordant for type I diabetes SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE immunoglobulin deficiency; type I diabetes; incomplete penetrance; major histocompatibility complex ID MAJOR HISTOCOMPATIBILITY COMPLEX; CONSERVED EXTENDED HAPLOTYPE; IGA DEFICIENCY; IDENTICAL-TWINS; INFECTION; CHILDREN; DISEASE; ASSOCIATION; ANTIBODIES; MELLITUS AB Incomplete intrinsic penetrance is the failure of some genetically susceptible individuals (e.g., monozygotic twins of those who have a trait) to exhibit that trait. For the first time, we examine penetrance of susceptibility genes for multiple MHC gene-determined traits in the same subjects. Serum levels of IgA, IgD, IgG3, but not IgG4, in 50 pairs of monozygotic twins discordant for type 1 diabetes (T1D) correlated more closely in the twins than in random paired controls. The frequencies of subjects deficient in IgA (6%), IgD (33%) and IgG4 (12%), but not in IgG3, were higher in the twins than in controls. We postulate that this was because the MHC haplotypes (and possible non-MHC genes) that predispose to T1D also carry susceptibility genes for certain immunoglobulin deficiencies. Immunoglobulin deficiencies were not associated with T1D. Pairwise concordance for the deficiencies in the twins was 50% for IgA, 57% for IgD and 50% for IgG4. There were no significant associations among the specific immunoglobulin deficiencies except that all IgA-deficient subjects had IgD deficiency. Thus, intrinsic penetrance is a random process independently affecting different MHC susceptibility genes. Because multiple different external triggers would be required to explain the results, differential environmental determinants appear unlikely. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. St Bartholomews Hosp, Dept Diabet & Metab, London, England. RP Alper, CA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM alper@cbr.med.harvard.edu FU NHLBI NIH HHS [P01 HL029583-200007, P01 HL029583, HL29583, P01 HL029583-200009, P01 HL029583-20] NR 36 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD SEP PY 2006 VL 27 IS 2 BP 89 EP 95 DI 10.1016/j.jaut.2006.07.007 PG 7 WC Immunology SC Immunology GA 100IK UT WOS:000241661500003 PM 17029885 ER PT J AU Koleva, RI Conley, BA Romero, D Riley, KS Marto, JA Lux, A Vary, CPH AF Koleva, Rositsa I. Conley, Barbara A. Romero, Diana Riley, Kristin S. Marto, Jarrod A. Lux, Andreas Vary, Calvin P. H. TI Endoglin structure and function - Determinants of endoglin phosphorylation by transforming growth factor-beta receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; BINDING PROTEIN ENDOGLIN; HUMAN ENDOTHELIAL-CELLS; I RECEPTORS; EXPRESSION ANALYSIS; MASS-SPECTROMETRY; EPITHELIAL-CELLS; KINASE-1 GENE; COMPLEX; ANGIOGENESIS AB Determination of the functional relationship between the transforming growth factor-beta(TGF beta) receptor proteins endoglin and ALK1 is essential to the understanding of the human vascular disease, hereditary hemorrhagic telangiectasia. TGF beta 1 caused recruitment of ALK1 into a complex with endoglin in human umbilical vein endothelial cells (HUVECs). Therefore, we examined TGF beta receptor-dependent phosphorylation of endoglin by the constitutively active forms of the TGF beta type I receptors ALK1, ALK5, and the TGF beta type II receptor, T beta RII. Of these receptors, T beta RII preferentially phosphorylated endoglin on cytosolic domain serine residues Ser(634) and Ser(635). Removal of the carboxyl-terminal tripeptide of endoglin, which comprises a putative PDZ-liganding motif, dramatically increased endoglin serine phosphorylation by all three receptors, suggesting that the PDZ-liganding motif is important for the regulation of endoglin phosphorylation. Constitutively active (ca) ALK1, but not caALK5, phosphorylated endoglin on cytosolic domain threonine residues. caALK1-mediated threonine phosphorylation required prior serine phosphorylation, suggesting a sequential mechanism of endoglin phosphorylation. Wild-type, but not a threonine phosphorylation-defective endoglin mutant blocked cell detachment and the antiproliferative effects of caALK1 expressed inHUVECs. These results suggest that ALK1 is a preferred TGF beta receptor kinase for endoglin threonine phosphorylation in HUVECs and indicate a role for endoglin phosphorylation in the regulation of endothelial cell adhesion and growth by ALK1. C1 Maine Med Ctr, Res Inst, Ctr Mol Med, Scarborough, ME 04074 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Hosp, D-68163 Mannheim, Germany. Univ Appl Sci, Inst Cell & Mol Biol, D-68163 Mannheim, Germany. RP Vary, CPH (reprint author), Maine Med Ctr, Res Inst, Ctr Mol Med, 81 Res Dr, Scarborough, ME 04074 USA. EM varyc@mmc.org FU PHS HHS [P20 15555] NR 60 TC 67 Z9 69 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25110 EP 25123 DI 10.1074/jbc.M601288200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300012 PM 16785228 ER PT J AU Wei, CC Zhang, SL Chen, YW Guo, DF Ingelfinger, JR Bomsztyk, K Chan, JSD AF Wei, Chih-Chang Zhang, Shao-Ling Chen, Yun-Wen Guo, Deng-Fu Ingelfinger, Julie R. Bomsztyk, Karol Chan, John S. D. TI Heterogeneous nuclear ribonucleoprotein K modulates angiotensinogen gene expression in kidney cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROXIMAL TUBULAR CELLS; DEPENDENT DIABETES-MELLITUS; PROTEIN-KINASE PATHWAY; RAT-KIDNEY; HNRNP-K; HIGH GLUCOSE; BINDING-PROTEIN; MESSENGER-RNA; MOLECULAR-CLONING; RESPONSE ELEMENT AB The present studies aimed to identify the 70-kDa nuclear protein that binds to an insulin-responsive element in the rat angiotensinogen gene promoter and to define its action on angiotensinogen gene expression. Nuclear proteins were isolated from rat kidney proximal tubular cells and subjected to two-dimensional electrophoresis. The 70-kDa nuclear protein was detected by Southwestern blotting and subsequently identified by mass spectrometry, which revealed that it was identical to 65-kDa heterogeneous nuclear ribonucleoprotein K (hnRNP K). hnRNP K bound to the insulin-responsive element of the rat angiotensinogen gene was revealed by a gel mobility shift assay and chromatin immunoprecipitation assay. hnRNP K inhibited angiotensinogen mRNA expression and promoter activity. In contrast, hnRNP K down-expression by small interference RNA enhanced angiotensinogen mRNA expression. Moreover, hnRNP K interacted with hnRNP F in pulldown and co-immunoprecipitation assays. Co-transfection of hnRNP K and hnRNP F further suppressed angiotensinogen mRNA expression. Finally, in vitro and in vivo studies demonstrated that high glucose increases and insulin inhibits hnRNP K expression in rat kidney proximal tubular cells. In conclusion, our experiments revealed that hnRNP K is a nuclear protein that binds to the insulin-responsive element of the rat angiotensinogen gene promoter and modulates angiotensinogen gene transcription in the kidney. C1 Ctr Hosp Univ Montreal, Hotel Dieu, Ctr Rech, Montreal, PQ H2W 1T8, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Chan, JSD (reprint author), Ctr Hosp Univ Montreal, Hotel Dieu, Ctr Rech, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK49578]; NIGMS NIH HHS [GM45134] NR 66 TC 16 Z9 16 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25344 EP 25355 DI 10.1074/jbc.M601945200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300036 PM 16837467 ER PT J AU Lammerding, J Fong, LG Ji, JY Reue, K Stewart, CL Young, SG Lee, RT AF Lammerding, Jan Fong, Loren G. Ji, Julie Y. Reue, Karen Stewart, Colin L. Young, Stephen G. Lee, Richard T. TI Lamins A and C but not lamin B1 regulate nuclear mechanics SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DREIFUSS MUSCULAR-DYSTROPHY; GILFORD-PROGERIA-SYNDROME; DILATED CARDIOMYOPATHY; BUILDING-BLOCKS; HUMAN-DISEASE; PRELAMIN-A; ENVELOPE; CELLS; LAMINOPATHIES; MUTATIONS AB Mutations in the nuclear envelope proteins lamins A and C cause a broad variety of human diseases, including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. Cells lacking lamins A and C have reduced nuclear stiffness and increased nuclear fragility, leading to increased cell death under mechanical strain and suggesting a potential mechanism for disease. Here, we investigated the contribution of major lamin subtypes (lamins A, C, and B1) to nuclear mechanics by analyzing nuclear shape, nuclear dynamics over time, nuclear deformations under strain, and cell viability under prolonged mechanical stimulation in cells lacking both lamins A and C, cells lacking only lamin A (i.e. "lamin C-only" cells), cells lacking wild-type lamin B1, and wild-type cells. Lamin A/C-deficient cells exhibited increased numbers of misshapen nuclei and had severely reduced nuclear stiffness and decreased cell viability under strain. Lamin C-only cells had slightly abnormal nuclear shape and mildly reduced nuclear stiffness but no decrease in cell viability under strain. Interestingly, lamin B1-deficient cells exhibited normal nuclear mechanics despite having a significantly increased frequency of nuclear blebs. Our study indicates that lamins A and C are important contributors to the mechanical stiffness of nuclei, whereas lamin B1 contributes to nuclear integrity but not stiffness. C1 Harvard Univ, Sch Med, Div Cardiovasc, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02139 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angelese Healthcare Syst, Los Angeles, CA 90073 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Lammerding, J (reprint author), Partners Res Facil, Rm 283,65 Landsdowne St, Cambridge, MA 02139 USA. EM jlammerding@rics.bwh.harvard.edu RI Lammerding, Jan/A-9498-2016 OI Lammerding, Jan/0000-0003-4335-8611 FU NCI NIH HHS [CA099506]; NHLBI NIH HHS [HL073809, HL64858, R01 HL082792]; NIAID NIH HHS [AI05438]; NIAMS NIH HHS [AR050200] NR 42 TC 199 Z9 203 U1 1 U2 29 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25768 EP 25780 DI 10.1074/jbc.M513511200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300079 PM 16825190 ER PT J AU Franceschini, MA Joseph, DK Huppert, TJ Diamond, SG Boas, DA AF Franceschini, Maria Angela Joseph, Danny K. Huppert, Theodore J. Diamond, Solomon G. Boas, David A. TI Diffuse optical imaging of the whole head SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE functional brain activation; diffuse optical imaging; optical system ID CEREBRAL HEMODYNAMICS; BRAIN; TOMOGRAPHY; TOPOGRAPHY; RESOLUTION; SYSTEM; ACTIVATION; REDUCTION; DESIGN; ADULTS AB Near-Infrared Spectroscopy (NIRS) and diffuse optical imaging (DOI) are increasingly used to detect hemodynamic changes in the cerebral cortex induced by brain activity. Until recently, the small number of optodes in NIRS instruments has hampered measurement of optical signals from diverse brain regions. Our new DOI system has 32 detectors and 32 sources; by arranging them in a specific pattern, we can cover most of the adult head. With the increased number of optodes, we can collect optical data from prefrontal, sensorimotor, and visual cortices in both hemispheres simultaneously. We describe the system and report system characterization measurements on phantoms as well as on human subjects at rest and during visual, motor, and cognitive stimulation. Taking advantage of the system's larger number of sources and detectors, we explored the spatiotemporal patterns of physiological signals during rest. These physiological signals, arising from cardiac, respiratory, and blood-pressure modulations, interfere with measurement of the hemodynamic response to brain stimulation. Whole-head optical measurements, in addition to providing maps of multiple brain regions' responses to brain activation, will enable better understandings of the physiological signals, ultimately leading to better signal processing algorithms to distinguish physiological signal clutter from brain activation signals. (c) 2006 Society of Photo- Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, NMR Martinos Ctr, Charlestown, MA 02129 USA. RP Franceschini, MA (reprint author), Massachusetts Gen Hosp, NMR Martinos Ctr, 13th St Bld 149,RM2301, Charlestown, MA 02129 USA. EM mari@nmr.mgh.harvard.edu OI Diamond, Solomon/0000-0002-7589-2942 FU NCI NIH HHS [R01 CA097305-03, R01 CA097305, R01 CA097305-04, T32 CA009502, T32-CA09502]; NCRR NIH HHS [P41 RR014075, P41 RR014075-08, P41-RR14075]; NIBIB NIH HHS [R01 EB001954, R01 EB001954-04A2, R01 EB001954-05, R01 EB002482, R01 EB002482-03, R01 EB002482-04, R01-EB001954, R01-EB002482]; NICHD NIH HHS [R01 HD042908] NR 20 TC 127 Z9 128 U1 0 U2 13 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2006 VL 11 IS 5 AR 054007 DI 10.1117/1.2363365 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 113DB UT WOS:000242576900011 PM 17092156 ER PT J AU Jones, PB Herl, L Berezovska, O Kumar, ATN Bacskai, BJ Hyman, BT AF Jones, Phill B. Herl, Lauren Berezovska, Oksana Kumar, Anand T. N. Bacskai, Brian J. Hyman, Bradley T. TI Time-domain fluorescent plate reader for cell based protein-protein interaction and protein conformation assays SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence spectroscopy; molecular spectroscopy ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; MICROSCOPY; PRESENILIN; FLUOROMETER; RELAXATION; MUTATIONS AB Fluorescence lifetime measurement is widely used in the biological sciences due to its inherent sensitivity and concentration independence. Frequency domain high-throughput plate readers and time-resolved energy transfer (TRET) plate readers are in common use and have been successful in a variety of applications ranging from basic biochemistry to drug discovery. Time-domain systems would have advantages due to their ability to distinguish both FRETing and non-FRETing populations, but have been difficult to develop due to inherent difficulties with background autofluorescence and lifetime component separation. Using a modified commercial lifetime plate reader, we demonstrate a method for removal of the complex autofluorescent background decay, described using a stretched exponential function (StrEF). We develop a generalized multi-exponential fitting algorithm (GeMEF), which progressively accounts for confounding lifetime components in FRET-based assays using a series of control experiments. We demonstrate the separability of FRET strength and efficiency and apply the technique to protein-protein interactions and protein conformational assays in a cell-based format. Presenilin 1 (PS1) is known to be important in Amyloid Precursor Protein (APP) processing in Alzheimer's disease. Using transfected cells, we demonstrate APP-PS1 interactions by FRET in a cell-based, 96-well plate format. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Disorders, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Jones, Phillip/0000-0003-0525-6323 FU NIA NIH HHS [1T0AG15379-08]; NIBIB NIH HHS [1R01EB00768] NR 27 TC 11 Z9 11 U1 0 U2 5 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2006 VL 11 IS 5 AR 054024 DI 10.1117/1.2363367 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 113DB UT WOS:000242576900028 PM 17092173 ER PT J AU Crichlow, RJ Andres, PL Morrison, SM Haley, SM Vrahas, MS AF Crichlow, Renn J. Andres, Patricia L. Morrison, Suzanne M. Haley, Stephen M. Vrahas, Mark S. TI Depression in orthopaedic trauma patients - Prevalence and severity SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FUNCTION ASSESSMENT QUESTIONNAIRE; NATIONAL COMORBIDITY SURVEY; ROAD TRAFFIC ACCIDENTS; HEALTH SURVEY SF-36; MAJOR TRAUMA; RECOVERY PROJECT; INJURY; INVENTORY; VALIDITY; CLASSIFICATION AB Background: There is a known connection between physical injury and disability and emotional distress. Several investigators have shown a relationship between trauma, depression, and poor outcomes. The literature on trauma and depression is limited with regard to clarifying the relationship between the degree of injury and depression and the relationship between physical function of patients with less severe injuries and depression. Methods: One hundred and sixty-one patients who presented to our orthopaedic trauma services were enrolled in the study and interviewed. We obtained information about patient demographics and administered several self-reported outcome measures: the Beck Depression Inventory (BDI), the Short Musculoskeletal Function Assessment (SMFA), and the Physical Function-10 (PF-10) subset of the Short Form-36 (SF-36). We documented the nature and severity of the injury or injuries and calculated correlations between the outcome measures and the BDI. Injury-specific factors such as the AO Fracture Classification, the Abbreviated Injury Scale (AIS), the Injury Severity Score (ISS), and the Gustilo and Anderson grade of open fractures were also examined. Results: Fifty-five percent of the patients had minimal depression, as measured with the BDI; 28% had moderate depression; 13% had moderate-to-severe depression; and 3.7% had severe depression. When the somatic elements of the BDI were removed, the prevalence of moderate, moderate-to-severe, or severe depression was 26%. The SMFA scores had a strong negative correlation with the BDI (-0.75; p < 0.001). Of the injury-specific factors, only open factures were found to have an impact on the presence of depression, with an odds ratio of 4.58 (95% confidence ratio, 1.57 to 12.35). Conclusions: The prevalence of clinically relevant depression approached 45% in a diverse cohort of orthopaedic trauma patients. Global disability is strongly correlated with depression. The presence of an open fracture may also increase the risk of depression. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. Partners Orthopaed Trauma Serv, Baltimore, MD 21201 USA. Boston Univ, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. RP Crichlow, RJ (reprint author), Partners Orthopaed Trauma Serv, 305 W Fayette St,Apartment 406, Baltimore, MD 21201 USA. EM mvrahas@partners.org NR 42 TC 59 Z9 59 U1 3 U2 6 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2006 VL 88A IS 9 BP 1927 EP 1933 DI 10.2106/JBJS.D.02604 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 083PO UT WOS:000240470900004 PM 16951107 ER PT J AU Ring, D Kadzielski, J Fabian, L Zurakowski, D Malhotra, LR Jupiter, JB AF Ring, David Kadzielski, John Fabian, Lauren Zurakowski, David Malhotra, Leah R. Jupiter, Jesse B. TI Self-reported upper extremity health status correlates with depression SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PAIN CATASTROPHIZING SCALE; IDIOPATHIC ARM PAIN; PERSONALITY; DISCREPANCIES; VALIDATION; COMPLAINTS; SYMPTOMS AB Background: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is the most widely used upper extremity-specific health-status measure. The DASH score often demonstrates greater variability than would be expected on the basis of objective pathology. This variability may be related to psychosocial factors. The purpose of the present study was to investigate the correlation between the DASH score and psychological factors for specific diagnoses with relatively limited variation in objective pathology. Methods: Two hundred and thirty-five patients with a single, common, discrete hand problem known to have limited variations in objective pathology completed the DASH questionnaire, the Eysenck Personality Questionnaire-Revised (EPQ-R) to assess neuroticism, the Center for Epidemiologic Studies-Depression (CES-D) scale to quantify depressive symptoms, and the Pain Anxiety Symptoms Scale (PASS). Forty-five patients had carpal tunnel syndrome, forty-four had de Quervain tenosynovitis, forty-eight had lateral elbow pain, and seventy-one had a single trigger finger. In addition, twenty-seven patients were evaluated six weeks after a nonoperatively treated fracture of the distal part of the radius. Relationships between psychosocial factors and the DASH score were determined. Results: A significant positive correlation between the DASH score and depression was noted for all diagnoses (r = 0.38 to 0.52; p < 0.01 for all). The DASH score also correlated with pain anxiety for four of the five diagnoses (carpal tunnel syndrome, r = 0.40; de Quervain tendinitis, r = 0.46; lateral elbow pain, r = 0.42; and trigger finger, r = 0.24) (p < 0.05 for all). The DASH score was not correlated with neuroticism for any diagnosis. There was a, highly significant effect of depression (as measured with the CES-D score) on the DASH score for all diagnoses. Both the CES-D score (F = 62.68, p < 0.0001) and gender (F = 11.36, p < 0.001) were independent predictors of the DASH score. Conclusions: Self-reported upper extremity-specific health status as measured with the DASH score correlates with depression and pain anxiety but not neuroticism. These data support the contention that psychosocial factors have a strong influence on health-status measures. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 19 TC 85 Z9 88 U1 3 U2 7 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 2006 VL 88A IS 9 BP 1983 EP 1988 DI 10.2106/JBJS.E.00932 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 083PO UT WOS:000240470900012 PM 16951115 ER PT J AU Hoch, B Inwards, C Sundaram, M Rosenberg, AE AF Hoch, Benjamin Inwards, Carrie Sundaram, Murali Rosenberg, Andrew E. TI Multicentric giant cell tumor of bone - Clinicopathologic analysis of thirty cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SKELETALLY IMMATURE PATIENTS; PULMONARY METASTASES; FOLLOW-UP; BENIGN; OSTEOCLASTOMA; RECURRENCE; DISEASE AB Background: Giant cell tumor of bone accounts for 4% to 5% of primary bone tumors. Approximately 1% of cases present as multiple synchronous or metachronous lesions. In this study, we describe the clinicopathologic features of thirty cases of multicentric giant cell tumor. Methods: Thirty patients who had two or more separate lesions that had been pathologically confirmed to be giant cell tumors were identified. Radiographs were reviewed to evaluate the characteristics and locations of the tumors. Histologic reexamination was performed to document morphologic features. Clinical information and follow-up data were obtained from the medical records. Results: The male:female ratio was 1:2, with an average age at presentation of twenty-one years. Fifty-nine percent of the patients were younger than twenty years of age. There were ninety-four tumors in the series, with an average of three (range, two to nine) per patient. Most tumors had arisen in the long bones. Six patients had synchronous ipsilateral involvement of the distal part of the femur and the proximal part of the tibia. Radiographically, the tumors in long bones manifested as expansive lytic lesions involving the metaphysis and extending into the epiphysis. A minority of the tumors were confined to the metaphysis, had features of a fibro-osseous or bone-forming lesion, or arose in skeletally immature patients. Secondary histopathologic changes including fibrohistiocytic regions, reactive bone formation, or aneurysmal bone cyst-like changes were not uncommon. Most tumors were treated with curettage (64%) or resection (22%). The recurrence rate was similar to that of solitary giant cell tumors. Metastatic disease developed in three patients, and two patients had malignant transformation. Conclusions: Multicentric giant cell tumors occur more often in younger patients than do solitary giant cell tumors, and they frequently present as synchronous lesions around the knee. Some tumors appear as bone-forming or fibro-osseous tumors on imaging studies as a result of fibrohistiocytic regions and reactive bone formation. The risk of recurrence depends on the type of surgery that is performed. Level of Evidence: Therapeutic Level IV See Instructions to Authors for a complete description of levels of evidence. C1 Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA. Mayo Clin, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44195 USA. RP Hoch, B (reprint author), Mt Sinai Med Ctr, Dept Pathol, Box 1194,1 Gustave L Levy Pl, New York, NY 10029 USA. EM benjamin.hoch@mountsinai.org NR 51 TC 38 Z9 47 U1 0 U2 1 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 2006 VL 88A IS 9 BP 1998 EP 2008 DI 10.2106/JBJS.E.01111 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 083PO UT WOS:000240470900014 PM 16951117 ER PT J AU Yeon, HB Lovett, DA Zurakowski, D Herndon, JH AF Yeon, Howard B. Lovett, David A. Zurakowski, David Herndon, James H. TI Physician discipline SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BOARD C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yeon, HB (reprint author), Massachusetts Gen Hosp, 55 Fruit St,VBK 210, Boston, MA 02114 USA. EM jherndon@partners.org NR 25 TC 3 Z9 3 U1 1 U2 1 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 2006 VL 88A IS 9 BP 2091 EP 2096 DI 10.2106/JBJS.F.00524 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 083PO UT WOS:000240470900025 PM 16951127 ER PT J AU Araujo, AB Travison, TG Link, CL Leder, BZ McKinlay, JB AF Araujo, A. B. Travison, T. G. Link, C. L. Leder, B. Z. McKinlay, J. B. TI Are there race/ethnic group differences in the association between sex steroids and bone mineral density in men? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 New England Res Inst, Watertown, MA 02172 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Travison, Thomas/C-7098-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S323 EP S323 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302370 ER PT J AU Banerjee, S Selim, A Suliman, G Juppner, H Bringhurst, F Divieti, P AF Banerjee, S. Selim, A. Suliman, G. Jueppner, H. Bringhurst, F. Divieti, P. TI Initial proteomic analysis of the partially purified carboxyl-PTH receptor(s) in bone cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S320 EP S320 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302360 ER PT J AU Bastepe, M Lorenz-Depiereux, B Bennet-Pages, A Ghassibe, M Wagenstaller, J Muller-Barth, U Badenhoop, K Rittmaster, R Shlossberg, A Olivares, J Ramos, F Vikkula, M Strom, T Juppner, H AF Bastepe, M. Lorenz-Depiereux, B. Bennet-Pages, A. Ghassibe, M. Wagenstaller, J. Mueller-Barth, U. Badenhoop, K. Rittmaster, R. Shlossberg, A. Olivares, J. Ramos, F. Vikkula, M. Strom, T. Jueppner, H. TI An autosomal recessive hypophosphatemic disorder caused by homozygous mutations in dentin matrix protein 1 (DMP1). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CSF Natl Res Ctr Environm & Hlth, Inst Human Genet, Munich, Germany. Christian de Duve Inst Cell Pathol, Brussels, Belgium. Univ Louvain, Sch Med, Brussels, Belgium. Univ Hosp, Frankfurt, Germany. QEII Hlth Sci Ctr, Halifax, NS, Canada. Univ Zaragoza, Fac Med, E-50009 Zaragoza, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S19 EP S19 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300065 ER PT J AU Battaglino, RA Spaete, U Morse, LR Pham, L Stashenko, P AF Battaglino, R. A. Spaete, U. Morse, L. R. Pham, L. Stashenko, P. TI PSTPIP1 silencing by si RNA alters osteoclast morphology and increases resorption in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S263 EP S263 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302139 ER PT J AU Battaglino, RA Pham, L Morse, LR Joe, M Sharma, A Stashenko, P AF Battaglino, R. A. Pham, L. Morse, L. R. Joe, M. Sharma, A. Stashenko, P. TI Cloning, expression and function of NHE-oc: A novel sodium/proton exchanger expressed in osteoclast mitochondria. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S66 EP S66 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300250 ER PT J AU Bergwitz, C Kremke, B Bounoutas, G Hiort, O Insogna, K Juppner, H AF Bergwitz, C. Kremke, B. Bounoutas, G. Hiort, O. Insogna, K. Jueppner, H. TI Hypophosphatemic rickets with hypercalciuria (HHRH) can be associated with renal stones. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Klinikum Schleswig Holstein, Lubeck, Germany. Yale Univ, Sch Med, Endocrine Unit, New Haven, CT 06520 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S312 EP S312 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302328 ER PT J AU Bischoff, DS Zhu, J Makhijani, NS Yamaguchi, DT AF Bischoff, D. S. Zhu, J. Makhijani, N. S. Yamaguchi, D. T. TI Acidic pH stimulates ELR+ CXC chemokine expression in human mesenchymal stem cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S363 EP S363 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303076 ER PT J AU Chen, W Yang, S Abe, Y Moroi, R Li, M Wang, Y Shao, J Li, YP AF Chen, W. Yang, S. Abe, Y. Moroi, R. Li, M. Wang, Y. Shao, J. Li, Y. P. TI A mouse model with pycnodysostosis phenotype reveals that Cathepsin K functions as a regulator of osteoclast apoptosis and senescence. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RI Yang, Shuying/G-4599-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S100 EP S100 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300381 ER PT J AU Cianferotti, L Demay, MB AF Cianferotti, L. Demay, M. B. TI Vitamin D receptor-mediated inhibition of Dkk1 and Sfrp2 suppresses adipogenic differentiation of bone marrow stromal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S5 EP S5 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300017 ER PT J AU Cory, E Nazarian, A Van der Zwaal, P Hoogwater, F Bohanske, M Snyder, B AF Cory, E. Nazarian, A. Van der Zwaal, P. Hoogwater, F. Bohanske, M. Snyder, B. TI DXA is unable to measure differential changes in bone density and microstructure induced by metabolic bone diseases. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Med, BIDMC, OBL, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S352 EP S352 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303037 ER PT J AU Crotti, TN Walsh, NC Barnes, GL Gerstenfeld, LC McHugh, KP AF Crotti, T. N. Walsh, N. C. Barnes, G. L. Gerstenfeld, L. C. McHugh, K. P. TI Neurofibromin expression in bone fracture healing. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S429 EP S429 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303335 ER PT J AU Dean, T Khatri, A Potetinova, Z Willick, G Gardella, TJ AF Dean, T. Khatri, A. Potetinova, Z. Willick, G. Gardella, T. J. TI Role of amino acid side chains in the (17-31) domain of parathyroid hormone in binding to the PTH receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. CNR, Inst Biol Sci, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S198 EP S198 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301315 ER PT J AU Divieti, PP Suliman, G Banerjee, S Harris, SE Bringhurst, FR AF Divieti, P. P. Suliman, G. Banerjee, S. Harris, S. E. Bringhurst, F. R. TI PTH receptors expression in primary osteocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S267 EP S267 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302154 ER PT J AU Garcia-Palacios, V Subler, MA Patrene, K Zhao, L Choi, SJ Blair, HC Windle, JJ Roodman, GD AF Garcia-Palacios, V. Subler, M. A. Patrene, K. Zhao, L. Choi, S. J. Blair, H. C. Windle, J. J. Roodman, G. D. TI A Disintegrin and Metalloprotease 8 (ADAM8) regulates osteoclast function in vitro and bone mass in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Virginia Commonwealth Univ, Richmond, VA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S42 EP S42 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300157 ER PT J AU Gori, F Zhu, ED Demay, MB AF Gori, F. Zhu, E. D. Demay, M. B. TI Wdr5, a BMP-2 induced gene, regulates bone volume postnatally. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S64 EP S64 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300243 ER PT J AU Kamiya, N Ward, T Ye, L Kobayashi, T Atsawasuwan, P Joiner, DM Waldorff, EI Kronenberg, HM Yamauchi, M Goldstein, S Feng, JQ Mishina, Y AF Kamiya, N. Ward, T. Ye, L. Kobayashi, T. Atsawasuwan, P. Joiner, D. M. Waldorff, E. I. Kronenberg, H. M. Yamauchi, M. Goldstein, S. Feng, J. Q. Mishina, Y. TI BMP signaling through type 1a receptor (BMPR1a/ALK3) regulates trabecular and cortical bone properties in an age, sex, and skeletal site dependent manner in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NIEHS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. Univ Missouri, Sch Dent, Kansas City, MO 64110 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ N Carolina, Dent Res Ctr, Chapel Hill, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S77 EP S77 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300295 ER PT J AU Kobayashi, T Karaplis, AC Goltzman, D Kronenberg, HM AF Kobayashi, T. Karaplis, A. C. Goltzman, D. Kronenberg, H. M. TI Bone is the primary target of PTH in regulation of fetal blood calcium. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McGill Univ, Sir Mortimer B Davis Jewish Hosp, Montreal, PQ, Canada. McGill Univ, Royal Victoria Hosp, Med Ctr, Montreal, PQ H3A 1A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S52 EP S52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300196 ER PT J AU Kobayashi, T Kronenberg, HM AF Kobayashi, T. Kronenberg, H. M. TI Small RNAs regulate chondrocyte differentiation in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S32 EP S33 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300118 ER PT J AU Kozloff, KM Quinti, L Tung, C Weissleder, R Mahmood, U AF Kozloff, K. M. Quinti, L. Tung, C. Weissleder, R. Mahmood, U. TI Non-invasive imaging of cathepsin K-Activated optical probe reveals osteoclast activity in vivo and in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Massachusetts Gen Hosp, CMIR, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S41 EP S41 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300153 ER PT J AU Leder, BZ Araujo, AB Travison, TG McKinlay, JB AF Leder, B. Z. Araujo, A. B. Travison, T. G. McKinlay, J. B. TI Biochemical markers of bone turnover and bone mineral density in black, hispanic, and white men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Res Inst, Watertown, MA USA. RI Travison, Thomas/C-7098-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S107 EP S107 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300407 ER PT J AU Linglart, A Bastepe, M Juppner, H AF Linglart, A. Bastepe, M. Juppner, H. TI Patients affected by the autosomal dominant and the sporadic form of pseudohypoparathyroidism type Ib (PHP-Ib) show a similar degree of PTH-Resistance. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Hop St Vincent de Paul, INSERM U561, F-75674 Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S119 EP S119 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301016 ER PT J AU Morse, LR Nyugen, H Jain, N Williams, S Tun, C Battaglino, R Stashenko, P Garshick, E AF Morse, L. R. Nyugen, H. Jain, N. Williams, S. Tun, C. Battaglino, R. Stashenko, P. Garshick, E. TI Age and motor score predict osteoprotegerin level in chronic SCI. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Med, PMR, Boston, MA 02115 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. Boston Med Ctr, PMR, Boston, MA USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S125 EP S125 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301040 ER PT J AU Napierala, D Sam, K Morello, R Zheng, O Bertin, T Shivdasani, R Lee, B AF Napierala, D. Sam, K. Morello, R. Zheng, O. Bertin, T. Shivdasani, R. Lee, B. TI Abnormal chondrocyte terminal differentiation and growth plate mineralization in the Trps1 mutant mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S19 EP S19 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300067 ER PT J AU Nishimori, S Kobayashi, T Kronenberg, HM AF Nishimori, S. Kobayashi, T. Kronenberg, H. M. TI Gene screening within the murine growth plate using DNA microarray. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S340 EP S340 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302439 ER PT J AU O'Brien, CA Plotkin, I Vyas, K Cazer, PE Gortazar, AR Goellner, JJ Chen, J Shelton, R Weinstein, RS Schipani, E Jilka, RL Manolagas, SC Bellido, T AF O'Brien, C. A. Plotkin, I. Vyas, K. Cazer, P. E. Gortazar, A. R. Goellner, J. J. Chen, J. Shelton, R. Weinstein, R. S. Schipani, E. Jilka, R. L. Manolagas, S. C. Bellido, T. TI Activation of PTH receptor 1 specifically in osteocytes suppresses sost expression and increases bone mass in transgenic mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S4 EP S4 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300013 ER PT J AU Ohishi, M Purton, LE Gunes, Y Marzia, M Scadden, DT Kronenberg, HM Schipani, E AF Ohishi, M. Purton, L. E. Gunes, Y. Marzia, M. Scadden, D. T. Kronenberg, H. M. Schipani, E. TI Constitutively active PTH/PTHrP receptor (PPR) in bone stromal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S198 EP S198 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301316 ER PT J AU Provot, S Zinyk, D Gunes, Y Kronenberg, HM Johnson, RS Longaker, MT Giaccia, AJ Schipani, E AF Provot, S. Zinyk, D. Gunes, Y. Kronenberg, H. M. Johnson, R. S. Longaker, M. T. Giaccia, A. J. Schipani, E. TI Hif-1alpha regulates differentiation of the limb bud mesenchyme and joint development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA USA. Univ Calif San Diego, Mol Biol Sect, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S49 EP S49 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300182 ER PT J AU Sitara, D Bergwitz, C Razzaque, MS Juppner, H Lanske, BKM AF Sitara, D. Bergwitz, C. Razzaque, M. S. Juppner, H. Lanske, B. K. M. TI In vivo molecular mechanisms of abnormal homeostasis in Fgf-23 null animals. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Dent Med, Dept Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S150 EP S150 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301136 ER PT J AU Vesco, KK Marshall, L Rizzo, JH Nelson, HD Humphrey, L Antoniucci, D Ensrud, K Hochberg, M Hillier, TA AF Vesco, K. K. Marshall, L. Rizzo, J. H. Nelson, H. D. Humphrey, L. Antoniucci, D. Ensrud, K. Hochberg, M. Hillier, T. A. TI Surgical menopause and risk for hip fracture in older women: The study of osteoporotic fractures. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Kaiser Ctr Hlth Res, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR 94143 USA. Univ Calif San Francisco, San Francisco, CA 55455 USA. Univ Minnesota, Minneapolis, MN 21201 USA. Univ Maryland, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S275 EP S275 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302184 ER PT J AU Withington, C Shimada, M AF Withington, C. Shimada, M. TI Overexpression of human calpastatin reduces osteoblastic proliferation, differentiation and mineralization. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S387 EP S387 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303168 ER PT J AU Wu, JY Kobayashi, T Rodda, S McMahon, AP Kronenberg, HM AF Wu, J. Y. Kobayashi, T. Rodda, S. McMahon, A. P. Kronenberg, H. M. TI Deletion of the G protein subunit Gs alpha in early osteoblasts results in fractures at birth. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S57 EP S57 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300214 ER PT J AU Wu, Y Ackerman, J Graham, L Glimcher, M AF Wu, Y. Ackerman, J. Graham, L. Glimcher, M. TI NMR measurement of hydroxyl ions in young and old bovine bone minerals. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S343 EP S343 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303003 ER PT J AU Yang, D Guo, J Shioda, T Devieti, P Bringhurst, F AF Yang, D. Guo, J. Shioda, T. Devieti, P. Bringhurst, F. TI Role of CITED1, a CBP/P300-Interacting protein, in regulation of osteoblastic differentiation by parathyroid hormone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Lab Tumor Biol, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S445 EP S445 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303390 ER PT J AU Yang, S Li, YP AF Yang, S. Li, Y. P. TI RGS10-Deficient mice exhibit severe osteopetrosis due to impaired osteoclast differentiation associated with loss of [Ca2+]i oscillations and NFAT2 expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RI Yang, Shuying/G-4599-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S23 EP S23 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300082 ER PT J AU Zickmund, SL Blasiole, JA Brase, V Arnold, RM AF Zickmund, Susan L. Blasiole, Julie A. Brase, Venture Arnold, Robert M. TI Congestive heart failure patients report conflict with their physicians SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE congestive heart failure; doctor-patient relationship; communication ID QUALITY-OF-LIFE; RESUSCITATION PREFERENCES; HEPATITIS-C; COMMUNICATION; SATISFACTION; CARE; MANAGEMENT; PREDICTORS; CLINICIAN; SYMPTOMS AB Background: Given the importance of the doctor-patient relationship, we examined the prevalence and nature of patients' perceived conflicts with the physicians caring for their congestive heart failure (CHF). Methods and Results: This cross-sectional study recruited patients with CHF in the outpatient and inpatient service of a tertiary referral hospital. Patients completed demographics, semistructured interviews, and surveys of emotional and health status. CHF physiologic measures and comorbidities were abstracted from the medical record. A team of 2 blinded coders analyzed the interviews. Thirty-one percent of the 289 patients reported difficulties with physicians. In the bivariate analysis, only marital status was significantly associated with conflict. Major problems included the providers' poor communication skills (20%), trust in the physicians' competence (18%), and insufficient medical information (16%). Patients identified care outside the tertiary referral hospital (13%) and inadequate communication between physicians (9%) as additional sources of difficulty. Conclusion: Perceived conflict with providers is common in patients with CHF. Patient-level factors, however, did not predict conflict, which differs from our previous findings with hepatitis C patients. Perceived conflict is troubling because it can undermine the trust in the doctor-patient relationship, thereby weakening the therapeutic bond necessary to care for this sick and often vulnerable population. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15260 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Zickmund, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 151C-U,Univ Dr C, Pittsburgh, PA 15240 USA. FU NHLBI NIH HHS [HL07121] NR 54 TC 10 Z9 10 U1 3 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD SEP PY 2006 VL 12 IS 7 BP 546 EP 553 DI 10.1016/j.cardfail.2006.03.008 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086YI UT WOS:000240708700009 PM 16952789 ER PT J AU Gohler, A Januzzi, JL Worrell, SS Osterziel, KJ Gazelle, GS Dietz, R Siebert, U AF Goehler, Alexander Januzzi, James L. Worrell, Stewart S. Osterziel, Karl Josef Gazelle, G. Scott Dietz, Rainer Siebert, Uwe TI A systematic meta-analysis of the efficacy and heterogeneity of disease management programs in congestive heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Review DE congestive heart failure; disease management program; meta-analysis; mortality; heterogeneity; publication bias ID HOME-BASED INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; ELDERLY-PATIENTS; MULTIDISCIPLINARY CARE; OLDER PATIENTS; HIGH-RISK; TELEPHONE INTERVENTION; UNPLANNED READMISSIONS; PUBLICATION BIAS; CLINICAL-TRIAL AB Background: We sought to systematically combine the evidence on efficacy of disease management programs (DMPs) in the treatment of congestive heart failure (CHF), to identify and explain heterogeneity of results from prior studies of DMPs, and to assess potential publication bias from these studies. Methods and Results: We conducted a systematic literature search on randomized clinical trials investigating the effect of DMPs on CHF outcomes and performed meta-analyses and meta-regressions comparing DMPs and standard care for mortality and rehospitalization. We included 36 studies from 13 different countries (with data from 8341 patients). Our meta-analysis yielded a pooled risk difference of 3%0 (95% confidence interval [CI] 1-6%, P < .01) for mortality and of 8% (95% CI 5-11%, P < .0001) for rehospitalization, both favoring DMP. Factors explaining heterogeneity between studies included severity of disease, proportion of beta-blocker at baseline, country, duration of follow-up, and mode of postdischarge contact. No statistically significant publication bias was detected. Conclusion: DMPs have the potential to reduce morbidity and mortality for patients with CHF. The benefit of the intervention depends on age, severity of disease, guideline-based treatment at baseline, and DMP modalities. Future studies should directly compare the effect of different aspects of disease management programs for different populations. C1 Harvard Univ, Sch Med, Cardiovasc Res Program, MGH Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Humboldt Med Sch, Div Cardiol, Berlin, Germany. Univ Hlth Sci, Dept Publ Hlth, Med Decis Making & Hlth Technol Assessment, UMIT, Hall In Tirol, Austria. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Siebert, U (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Program, MGH Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. NR 62 TC 101 Z9 105 U1 5 U2 12 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD SEP PY 2006 VL 12 IS 7 BP 554 EP 567 DI 10.1016/j.cardfail.2006.03.003 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086YI UT WOS:000240708700010 PM 16952790 ER PT J AU Dukkipati, S Holmvang, G Scozzaro, M D'Avila, A Reddy, VY Mansour, M AF Dukkipati, Srinivas Holmvang, Godtfred Scozzaro, Matthew D'Avila, Andre Reddy, Vivek Y. Mansour, Moussa TI An unusual confluence of the inferior pulmonary veins in a patient undergoing catheter ablation for atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2006 VL 17 IS 9 BP 1034 EP 1034 DI 10.1111/j.1540-8167.2006.00527.x PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 072SA UT WOS:000239692100023 PM 16759296 ER PT J AU Wadhani, N Sarma, JSM Singh, BN Radzik, D Gaud, C AF Wadhani, Nitin Sarma, Jonnalagedda S. M. Singh, Bramah N. Radzik, David Gaud, Christine TI Dose-dependent effects of oral dronedarone on the circadian variation of RR and QT intervals in healthy subjects: Implications for antiarrhythmic actions SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE dronedarone; QT circadian rhythm; antiarrhythmic agent ID ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; AMIODARONE; SR-33589; AGENT; CELLS; HEART; ADRENOCEPTOR; DOGS AB Dronedarone, a non-iodinated benzofuran derivative, was developed as a potentially less toxic alternative to amiodarone. This study describes Holter data of dronedarone in humans. Five groups of healthy subjects were given I of 5 oral doses of dronedarone in a twice-daily regimen or placebo. Holter recordings of circadian rhythmicity of RR and QT intervals were evaluated. Dronedarone prolonged RR and QT intervals as a function of dose, without effect on circadian patterns. The relative prolongation of QT, QTc, and RR by dronedarone was significant. The QTc interval did not exhibit a clearly recognizable circadian pattern, suggesting that the circadian pattern of the QT interval was mostly a reflection of circadian changes in the RR interval in the study population. Dronedarone resembled amiodarone in class III and sympatholytic effects, indicating its potential as a unique antiarrhythmic compound seemingly devoid of the side effects mediated by iodine in amiodarone. C1 VA Greater Los Angeles Area Healthcare Syst, Cardiol Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Sanofi Aventis, Chilly Mazarin, France. RP Singh, BN (reprint author), VA Greater Los Angeles Area Healthcare Syst, Cardiol Sect, 111E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM bsingh@ucla.edu NR 19 TC 8 Z9 9 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD SEP PY 2006 VL 11 IS 3 BP 184 EP 190 DI 10.1177/1074248406290678 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 095NI UT WOS:000241314200004 PM 17056831 ER PT J AU Ghanem, RC Azar, DT AF Ghanem, Ramon C. Azar, Dimitri T. TI Femtosecond-laser arcuate wedge-shaped resection to correct high residual astigmatism after penetrating keratoplasty SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID POSTKERATOPLASTY ASTIGMATISM; SURGICAL-CORRECTION; INTRAOCULAR-LENS; SURGERY; IMPLANTATION; TRIPLE AB We describe a standardized technique of femtosecond (FS) laser arcuate resection (LAR) in which intersecting arcuate cuts are used to perform a wedge resection for the correction of high astigmatism. A simple formula was used to calculate the relative decentration of the arcuate cuts based on the radii of curvature and desired wedge width to be resected. Feasibility of the procedure was established in porcine corneas before treatment of a patient with 20 diopters (D) of post-keratoplasty astigmatism. The astigmatism was reversed. Suture removal resulted in reduction of 14.5 D of astigmatism. Laser arcuate resection can be an effective alternative to manual wedge resection, allowing easier, more controlled, and more precise excision of tissue in width, length, and depth. C1 Univ Illinois, Corneal External Dis & Refract Surg Serv, Chicago, IL 60680 USA. UIC Dept Ophthalmol & Visual Sci, Chicago, IL USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Azar, DT (reprint author), Univ Illinois, Corneal External Dis & Refract Surg Serv, Chicago, IL 60680 USA. EM dazar@uic.edu FU NEI NIH HHS [EY10101] NR 23 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2006 VL 32 IS 9 BP 1415 EP 1419 DI 10.1016/j.jcrs.2006.02.083 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 081NT UT WOS:000240325000016 PM 16931248 ER PT J AU Subramanian, M Kuang, PP Wei, L Rishikof, DC Liu, H Goldstein, RH AF Subramanian, Mangalalaxmy Kuang, Ping-Ping Wei, Lin Rishikof, David C. Liu, Hanqiao Goldstein, Ronald H. TI Modulation of amino acid uptake by TGF-beta in lung myofibroblasts SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE amino acid transport; transforming growth factor-beta; phosphatidylinositol 3-kinase; lung; fibroblast ID SMOOTH-MUSCLE-CELLS; TRANSPORT SYSTEM-A; GROWTH-FACTOR; ADAPTIVE REGULATION; SKELETAL-MUSCLE; GENE-EXPRESSION; INSULIN; FIBROBLASTS; SUBTYPE; ATA2 AB Hormones such as insulin, growth factors, and cell stress stimulate system A amino acid transporter. Transforming growth factor-beta (TGF-beta) stimulates amino acid uptake thereby inducing cell proliferation, cellular hypertrophy, and matrix synthesis. Insulin appears to activate amino acid in smooth muscle cells via a phosphaticlylinositol 3-kinase (PI3-kinase)-dependent pathway. We examine the effect and interaction of TGF-beta, insulin, and PI3-kinase activity on amino acid uptake in human lung myofibroblasts. TGF-beta treatment induced large increases in system A activity and a small delayed increase in the phosphorylation of protein kinase 13, also termed phospho-Akt. In contrast, insulin induced small increases in system A activity and large increases in phospho-Akt levels. LY294002, a PI3-kinase inhibitor, blocked the TGF-beta-induced amino acid uptake only partially, but completely blocked TGF-beta-induced Akt phosphorylation. Moreover, the level of phospho-Smad3 was found to be high even when LY294002 blocked TGF-beta-induced phospho-Akt levels. Inhibition of PI3-kinase activity resulted in increase in K-m, consistent with a major change in transporter activity without change in transporter number. The PI3-kinase inhibitor also did not change the amino acid transporter 2 (ATA2) mRNA levels. Taken together, these results suggest that TGF-beta induced Smad-3 and amino acid uptake through a PI3-kinase independent pathway. C1 Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA. Boston VA Healthcare Syst, Dept Med, Div Pulm Med, Boston, MA USA. RP Subramanian, M (reprint author), Boston Univ, Sch Med, Ctr Pulm, Dept Med, 715 Albany St,R-304, Boston, MA 02118 USA. EM ramyats@abu.edu FU NHLBI NIH HHS [P01-HL46902, R01-HL70182, HL66547, HL49602] NR 23 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 1 PY 2006 VL 99 IS 1 BP 71 EP 78 DI 10.1002/jcb.20849 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 077TE UT WOS:000240052400005 PM 16598748 ER PT J AU Da Silva, APB Pollett, A Rittling, SR Denhardt, DT Sodek, J Zohar, R AF Da Silva, Andre Paes Batista Pollett, Aaron Rittling, Susan R. Denhardt, David T. Sodek, Jaro Zohar, Ron TI Exacerbated tissue destruction in DSS-induced acute colitis of OPN-null mice is associated with downregulation of TNF-alpha expression and non-programmed cell death SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID DEXTRAN SULFATE SODIUM; INFLAMMATORY-BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA; OSTEOPONTIN-DEFICIENT MICE; ULCERATIVE-COLITIS; IMMUNE-RESPONSE; MURINE COLITIS; CROHNS-DISEASE; T-CELLS; IN-VIVO AB Osteopontin (OPN), a pro-inflammatory mediator, is constitutively expressed in normal gut and is upregulated in inflammatory colitis. To determine the significance of OPN in inflammatory bowel disease, we studied the development of acute, experimental colitis induced by dextran sulfate sodium (DSS) in OPN-null and wild-type (WT) mice. OPN expression was markedly increased in WT diseased colons, while a higher disease activity index, including spleen enlargement, bowel shortening, and mucosal destruction, was observed in OPN-null mice. Although peripheral blood neutrophil numbers were lower in DSS-treated OPN-null mice, tissue myeloperoxidase levels, reflecting enhanced neutrophil activity, were increased in the diseased colons. In comparison, lymphocyte numbers in peripheral blood were increased earlier than in DSS-treated WT mice. Despite a significantly greater spleen enlargement, flow cytometric analysis of splenocytes from the DSS-treated OPN-null mice revealed lower numbers of differentiated macrophages and (CD4+ and CD8 alpha+) lymphocytes. Whereas pro-inflammatorycytokines, including G-CSF, RANTES, MIP1 alpha, and TNF-alpha, were increased < 10-fold in DSS-treated WT splenocytes, expression of these cytokines was dramatically suppressed in the DSS-treated OPN-null splenocytes as well as gut tissues. The suppressed TNF-a response in OPN-null mice was reflected in a marked increase in non-apoptotic cell death in diseased colons. Collectively, these studies demonstrate that OPN is required for mucosal protection in acute inflammatory colitis. C1 Univ Toronto, Fac Dent, Toronto, ON M5G 1G6, Canada. Univ Toronto, Fac Med, Dept Biochem, Toronto, ON, Canada. Univ Toronto, CIHR Grp Matrix Dynam, Toronto, ON, Canada. Mt Sinai Hosp, Dept Pathol, Toronto, ON M5G 1X5, Canada. Harvard Univ, Forsyth Dent Inst, Boston, MA USA. Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. RP Zohar, R (reprint author), Univ Toronto, Fac Dent, 124 Edward St, Toronto, ON M5G 1G6, Canada. EM ron.zohar@utoronto.ca RI Pollett, Aaron/J-2308-2016 OI Pollett, Aaron/0000-0001-5121-8788 NR 79 TC 39 Z9 39 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2006 VL 208 IS 3 BP 629 EP 639 DI 10.1002/jcp.20701 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 068YW UT WOS:000239412300017 PM 16741956 ER PT J AU Eichler, F Tan, WH Shih, VE Grant, PE Krishnamoorthy, K AF Eichler, Florian Tan, Wen-Hann Shih, Vivian E. Grant, P. Ellen Krishnamoorthy, Kalpathy TI Proton magnetic resonance spectroscopy and diffusion-weighted imaging in isolated sulfite oxidase deficiency SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID MR SPECTROSCOPY; BRAIN AB Isolated sulfite oxidase deficiency is a rare autosomal recessive disorder of the newborn that can be mistaken for neonatal asphyxia. Diffusion-weighted imaging of the brain demonstrates widespread diffusion restriction, and proton magnetic resonance spectroscopy shows an elevated lactate level, a decrease in the ratio of N-acetylaspartate to creatine, and a rise in the ratio of choline to creatine. This precedes severe cystic encephalomalacia and suggests that the energy failure associated with neuronal dysfunction and myelin disintegration occurs early in isolated sulfite oxidase deficiency. C1 Harvard Univ, Dept Neurol, Div Child Neurol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. Harvard Univ, Sch Med, Genet Training Program, Boston, MA 02114 USA. Harvard Univ, Dept Radiol, Div Child Neurol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Krishnamoorthy, K (reprint author), Harvard Univ, Dept Neurol, Div Child Neurol, Massachusetts Gen Hosp,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM kkrishnamoorthy@partners.org NR 11 TC 11 Z9 11 U1 0 U2 0 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 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2006 VL 21 IS 9 BP 801 EP 805 DI 10.2310/7010.2006.00174 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 102KV UT WOS:000241810800016 PM 16970890 ER PT J AU Monuteaux, MC Blacker, D Biederman, J Fitzmaurice, G Buka, SL AF Monuteaux, Michael C. Blacker, Deborah Biederman, Joseph Fitzmaurice, Garrett Buka, Stephen L. TI Maternal smoking during pregnancy and offspring overt and covert conduct problems: a longitudinal study SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE conduct disorder; overt; covert; maternal smoking ID OPPOSITIONAL DEFIANT DISORDER; VIOLENCE; PSYCHOPATHOLOGY; COMPLICATIONS; AGGRESSION; SEROTONIN; BEHAVIOR; CRIME; RISK; BOYS AB Background: Empirical evidence demonstrates that conduct disorder ( CD) symptoms tend to cluster into covert and overt domains. We hypothesized that overt and covert CD symptoms may be distinct constructs with distinct risk factors. An important risk factor for CD is maternal smoking during pregnancy. We further investigated this association, attending to overt and covert CD symptom subtypes. Also, we tested whether gender and socioeconomic status (SES) modified this association. Method: Participants were male and female adult offspring (n = 682) of a community sample of pregnant women followed longitudinally from prenatal life to age 22. Prospective assessments of maternal smoking during pregnancy were used to predict self-reported DSM-III CD symptoms. Results: Prenatal exposure to smoking was significantly associated with increased overt CD symptoms for participants of low SES, but not for participants of high SES, whereas covert CD symptoms were not associated with prenatal exposure. Gender did not significantly modify the relationship between maternal smoking and CD symptom subtypes. Conclusions: These results suggest that the previously documented association between maternal smoking and CD may be specific to overt CD symptoms, providing support for the heuristic value of differentiating overt and covert CD symptoms as distinct syndromes. These findings further support smoking prevention programs for pregnant women. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Program, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. RP Monuteaux, MC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Program, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM mmonuteaux@partners.org RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 28 TC 25 Z9 25 U1 3 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD SEP PY 2006 VL 47 IS 9 BP 883 EP 890 DI 10.1111/j.1469-7610.2005.01566.x PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 076EZ UT WOS:000239941100003 PM 16930382 ER PT J AU Misra, S Kimball, WR AF Misra, Sutanu Kimball, william R. TI Pneumothorax during argon beam-enhanced coagulation in laparoscopy SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE argon beam coagulation; hemorrhage; pneumothorax; surgery, laparoscopic ID PARTIAL NEPHRECTOMY AB Argon beam coagulation is an effective modality to control rapid diffuse hemorrhage. We present a case of pneumothorax. from argon beam coagulation used during laparoscopic surgery. We discuss potential cardiopulmonary consequences of this relatively new application of argon beam technology. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Misra, S (reprint author), Anesthesia Associates Kent Cty, POB 7032, Warwick, RI 02887 USA. EM sutanumisra@hotmail.com NR 8 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 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 2006 VL 18 IS 6 BP 446 EP 448 DI 10.1016/j.jclinane.2005.12.012 PG 3 WC Anesthesiology SC Anesthesiology GA 091JF UT WOS:000241022600009 PM 16980162 ER PT J AU Mitsiades, CS Kotoula, V Poulaki, V Sozopoulos, E Negri, J Charalambous, E Fanourakis, G Voutsinas, G Tseleni-Balafouta, S Mitsiades, N AF Mitsiades, Constantine S. Kotoula, Vassiliki Poulaki, Vassiliki Sozopoulos, Elias Negri, Joseph Charalambous, Elpida Fanourakis, Galinos Voutsinas, Gerassimos Tseleni-Balafouta, Sophia Mitsiades, Nicholas TI Epidermal growth factor receptor as a therapeutic target in human thyroid carcinoma: Mutational and functional analysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CELL LUNG-CANCER; PHASE-III TRIAL; MOLECULAR THERAPY; EGFR MUTATIONS; GEFITINIB; TUMORS; ERLOTINIB; CARBOPLATIN; PACLITAXEL; INHIBITOR AB Context: The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues. EGFR inhibitors have produced objective responses in patients with non-small-cell lung carcinomas harboring activating EGFR TK domain somatic mutations. Objective and Methods: Because the EGFR pathway has been reported to be important for the pathophysiology of thyroid carcinoma, we investigated the expression and mutational status of EGFR in 14 thyroid carcinoma cell lines as well as its functional role by evaluating their in vitro sensitivity to AEE788, a new dual-family EGFR/ErbB2 and vascular endothelial growth factor receptor TK inhibitor. We also evaluated the mutational status, mRNA and protein expression, as well as phosphorylation status of EGFR in a panel of thyroid carcinoma specimens. Results: EGFR expression and phosphorylation in the thyroid carcinoma cell lines and tissue specimens were present but not stronger than in noncancerous thyroid tissue. EGFR TK domain mutations were detected in two of 62 histological specimens (3.2%) but not in cell lines. All thyroid carcinoma cell lines were significantly less sensitive (IC(50) at least 25-fold higher) in vitro to AEE788 than a primary culture of EGFR-mutant lung carcinoma cells. Conclusions: Thyroid carcinoma cells overall are poorly responsive to clinically relevant concentrations of AEE788 in vitro. The presence of EGFR-activating TK domain mutations may identify a small minority of thyroid cancer patients that may benefit from EGFR inhibitors, but additional preclinical evidence of efficacy is needed. C1 Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Aristotle Univ Thessaloniki, Sch Med, Dept Pathol, GR-54006 Thessaloniki, Greece. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Athens, Dept Pathol, Athens 11527, Greece. NCSR Demokritos, Inst Biol, Lab Environm Mutagenesis & Carcinogenesis, GR-15310 Athens, Greece. RP Mitsiades, CS (reprint author), Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst, Mayer Bldg,Room M555,44 Binney St, Boston, MA 02115 USA. EM Constantine_Mitsiades@dfci.harvard.edu NR 21 TC 45 Z9 47 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 2006 VL 91 IS 9 BP 3662 EP 3666 DI 10.1210/jc.2006-0055 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 082AL UT WOS:000240358600066 PM 16822827 ER PT J AU Bini, EJ Currie, SL Shen, H Brau, N Schmidt, W Anand, BS Cheung, R Wright, TL AF Bini, Edmund J. Currie, Sue L. Shen, Hui Brau, Norbert Schmidt, Warren Anand, Bhupinderjit S. Cheung, Ramsey Wright, Teresa L. CA VA HCV 001 Study Grp TI National multicenter study of HIV testing and HIV seropositivity in patients with chronic hepatitis C virus infection SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE HIV; AIDS; hepatitis C; testing; multicenter studies; epidemiology ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CLINICAL-TRIALS GROUP; UNITED-STATES; LIVER-DISEASE; COINFECTED PATIENTS; COST-EFFECTIVENESS; MORTALITY; PROGRESSION; PREVALENCE AB Background: Although HIV testing is recommended for persons with hepatitis C virus (HCV) infection who are at risk for HIV, little is known about HIV testing in this population. Methods: Data were prospectively collected in 4364 HCV-infected patients at 24 Veterans Affairs medical centers across the United States, including demographics, risk factors for HIV infection, and self-reported information on HIV testing. Results: Overall, 76.8% had been tested for HIV at least once, 14.8% were never tested, 6.6% did not know if they were tested, and 1.8% declined to answer. Multivariable analysis identified injection drug use, needlestick injury, sex with a same-sex partner, a greater number of lifetime sexual partners, and sex with an injection drug user as factors that were independently associated with HIV testing. At least one risk factor for HIV infection was present in 84.5% of the 646 patients who were never HIV tested. Among the 3350 subjects who were tested for HIV, 8.4% were positive, 88.3% were negative, 2.4% did not know the results of their test, and 0.9% declined to answer. Multivariable analysis identified African American and Hispanic race/ethnicity, income <=$10,000, sex with a same-sex partner, and sex with an injection drug user as the only variables that were independently associated with HIV seropositivity. Conclusions: Although a substantial proportion of HCV-infected patients have been tested for HIV, missed opportunities for early diagnosis of HIV infection exist. Public health strategies to improve HIV testing among patients with chronic HCV infection are needed. C1 VA New York Harbor Healthcare Syst, Div Gastroenterol, New York, NY 10010 USA. NYU, Sch Med, New York, NY USA. VA Med Ctr, San Francisco, CA USA. VA Med Ctr, Boston, MA USA. VA Med Ctr, Palo Alto, CA USA. VA Med Ctr, Iowa City, IA USA. VA Med Ctr, Houston, TX USA. RP Bini, EJ (reprint author), VA New York Harbor Healthcare Syst, Div Gastroenterol, 423 E 23rd St, New York, NY 10010 USA. EM Edmund.Bini@med.va.gov NR 45 TC 8 Z9 8 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2006 VL 40 IS 8 BP 732 EP 739 DI 10.1097/00004836-200609000-00014 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 079FC UT WOS:000240159900014 PM 16940888 ER PT J AU Deng, JC Cheng, GH Newstead, MW Zeng, XY Kobayashi, K Flavell, RA Standiford, TJ AF Deng, Jane C. Cheng, Genhong Newstead, Michael W. Zeng, Xianying Kobayashi, Koichi Flavell, Richard A. Standiford, Theodore J. TI Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ANTIBACTERIAL HOST-DEFENSE; TUMOR-NECROSIS-FACTOR; INFLAMMATORY RESPONSE SYNDROME; MURINE KLEBSIELLA PNEUMONIA; ORGAN DYSFUNCTION SYNDROME; RECEPTOR-ASSOCIATED KINASE; PSEUDOMONAS-AERUGINOSA; NEUTROPHIL RECRUITMENT; INTERLEUKIN-1 RECEPTOR; MONOCYTE DEACTIVATION AB Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic patients and experimental animals display a "deactivated" phenotype, characterized by impaired inflammatory and antimicrobial responses, including hyporesponsiveness to LPS. We investigated the role of the LPS/TLR4 axis and its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), in modulating the immunosuppression of sepsis using a murine model of peritonitis-induced sepsis followed by secondary challenge by intratracheal Pseudomonas aeruginosa. Septic mice demonstrated impaired alveolar macrophage function and increased mortality when challenged with intratracheal Pseudomonas as compared with nonseptic controls. TLR2 and TLR4 expression was unchanged in the lung following sepsis, whereas levels of IRAK-M were upregulated. Macrophages from IRAK-M-deficient septic mice produced higher levels of proinflammatory cytokines ex vivo and greater costimulatory molecule expression in vivo as compared with those of their WT counterparts. Following sepsis and secondary intrapulmonary bacterial challenge, IRAK-M-/- animals had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice. In addition, increased pulmonary chemokine and inflammatory cytokine production was observed in IRAK-M-/- animals, leading to enhanced neutrophil recruitment to airspaces. Collectively, these findings indicate that IRAK-M mediates critical aspects of innate immunity that result in an immunocompromised state during sepsis. C1 Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Univ Michigan, Ctr Med, Div Pulm & Crit Care Med, Dept Med, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT USA. Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Deng, JC (reprint author), Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, David Geffen Sch Med, 10833 LeConte Ave,37-131 CHS, Los Angeles, CA 90095 USA. EM jdeng@mednet.ucla.edu FU NHLBI NIH HHS [K08 HL081229, K08HL081229, P050 HL60289, R01 HL057243, HL57243] NR 61 TC 136 Z9 140 U1 0 U2 5 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 2006 VL 116 IS 9 BP 2532 EP 2542 DI 10.1172/JCI28054 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 082IT UT WOS:000240380700029 PM 16917541 ER PT J AU Chen, CY Chi, KH George, RW Cox, DL Srivastava, A Silva, MR Carneiro, F Lauwers, GY Ballard, RC AF Chen, Cheng-Yen Chi, Kai-Hua George, Robert W. Cox, David L. Srivastava, Amitabh Silva, Mario Rui Carneiro, Fatima Lauwers, Gregory Y. Ballard, Ronald C. TI Diagnosis of gastric syphilis by direct immunofluorescence staining and real-time PCR testing SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; TREPONEMA-PALLIDUM; DNA AB We report on a case of gastric syphilis in a patient with chronic dyspepsia. The diagnosis was established by serology and the demonstration of spirochetes in diffusely inflammed gastric mucosa by staining with a fluorescent monoclonal antibody specific for pathogenic treponemes and by the detection of specific treponemal DNA sequences by a real-time PCR. C1 Ctr Dis Control & Prevent, Div STD Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Hosp Coimbra, Dept Pathol, Coimbra, Portugal. Univ Porto, Inst Mol Pathol & Immunol, P-4100 Oporto, Portugal. Fac Med HS Joao, Oporto, Portugal. RP Chen, CY (reprint author), Ctr Dis Control & Prevent, Div STD Prevent, Natl Ctr HIV STD & TB Prevent, Mail Stop G-39,1600 Clifton Rd, Atlanta, GA 30333 USA. EM cycl@cdc.gov RI Srivastava, Amitabh/A-9386-2009; Carneiro, Fatima/J-6432-2013 OI Carneiro, Fatima/0000-0002-1964-1006 NR 10 TC 23 Z9 24 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2006 VL 44 IS 9 BP 3452 EP 3456 DI 10.1128/JCM.00721-06 PG 5 WC Microbiology SC Microbiology GA 086YB UT WOS:000240708000072 PM 16954299 ER PT J AU Hayes, DF Picard, MH AF Hayes, Daniel F. Picard, Michael H. TI Heart of darkness: The downside of trastuzumab SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID METASTATIC BREAST-CANCER; TRIAL COMPARING DOXORUBICIN; MONOCLONAL-ANTIBODY; RANDOMIZED-TRIAL; PHASE-II; ADJUVANT CHEMOTHERAPY; CARDIOTOXICITY; RECEPTOR; PLUS; HER2 C1 Univ Michigan, Breast Oncol Program, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hayes, DF (reprint author), Univ Michigan, Breast Oncol Program, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. OI Picard, Michael/0000-0002-9264-3243 FU NCI NIH HHS [R01 CA92461] NR 27 TC 37 Z9 40 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2006 VL 24 IS 25 BP 4056 EP 4058 DI 10.1200/JCO.2006.07.5143 PG 3 WC Oncology SC Oncology GA 081LV UT WOS:000240320000004 PM 16908930 ER PT J AU Guadagnolo, BA Punglia, RS Kuntz, KM Mauch, PM Ng, AK AF Guadagnolo, Beverly A. Punglia, Rinaa S. Kuntz, Karen M. Mauch, Peter M. Ng, Andrea K. TI Cost-effectiveness analysis of computerized tomography in the routine follow-up of patients after primary treatment for Hodgkin's disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol ID POSITRON-EMISSION-TOMOGRAPHY; STEM-CELL TRANSPLANTATION; BONE-MARROW TRANSPLANTATION; HIGH-DOSE THERAPY; INVOLVED-FIELD RADIOTHERAPY; EARLY-STAGE; WHOLE-BODY; FDG-PET; SALVAGE CHEMOTHERAPY; FAVORABLE-PROGNOSIS AB Purpose To estimate the clinical benefits and cost effectiveness of computed tomography (CT) in the follow-up of patients with complete response (CR) after treatment for Hodgkin's disease (HD). Patients and Methods We developed a decision-analytic model to evaluate follow-up strategies for two hypothetical cohorts of 25-year-old patients with stage I-II or stage III-IV HD, treated with doxorubicin, bleomycin, vinblastine, and dacarbazine-based chemotherapy with or without radiation therapy, respectively. We compared three strategies for observing asymptomatic patients after CR: routine annual CT for 10 years, annual CT for 5 years, or follow-up with non-CT modalities only. We used Markov models to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies. Cost data were derived from the Medicare fee schedule and medical literature. We performed sensitivity analyses by varying baseline estimates. Results Annual CT follow-up is associated with minimal survival benefit. With adjustments for quality of life, we found a decrement in quality-adjusted life expectancy for early-stage patients followed with CT compared with non-CT modalities. Sensitivity analyses showed annual CT for 5 years becomes more effective than non-CT follow-up if the specificity of CT is 80% or more or if the disutility associated with a false-positive CT result is less than 0.01 quality-adjusted life years (QALYs). For advanced-stage patients, annual CT for 5 years is associated with a very small quality-adjusted survival gain over non-CT follow-up with an incremental cost-effectiveness ratio of $9,042,300/QALY. Conclusion Our analysis suggests that routine CT should not be used in the surveillance of asymptomatic patients in CR after treatment for HD. C1 Harvard Univ, Joint Ctr Radiat Therapy, Harvard Radiat Oncol Program, Boston, MA 02215 USA. Harvard Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02215 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Guadagnolo, BA (reprint author), Harvard Univ, Dept Radiat Oncol, 375 Longwood Ave, Boston, MA 02215 USA. EM aguadagnolo@post.harvard.edu FU NCI NIH HHS [5 R25 CA57711-11] NR 48 TC 40 Z9 40 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2006 VL 24 IS 25 BP 4116 EP 4122 DI 10.1200/JCO.2006.07.0409 PG 7 WC Oncology SC Oncology GA 081LV UT WOS:000240320000013 PM 16943528 ER PT J AU Baron, F Storb, R Storer, BE Maris, MB Niederwieser, D Shizuru, JA Chauncey, TR Bruno, B Forman, SJ McSweeney, PA Maziarz, RT Pulsipher, MA Agura, ED Wade, J Sorror, M Maloney, DG Sandmaier, BM AF Baron, Frederic Storb, Rainer Storer, Barry E. Maris, Michael B. Niederwieser, Dietger Shizuru, Judith A. Chauncey, Thomas R. Bruno, Benedetto Forman, Stephen J. McSweeney, Peter A. Maziarz, Richard T. Pulsipher, Michael A. Agura, Edward D. Wade, James Sorror, Mohamed Maloney, David G. Sandmaier, Brenda M. TI Factors associated with outcomes in allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning after failed myeloablative hematopoietic cell transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 7th Conference on Process Integration Modeling and Optimization for Energy Saving and Pollution Reduction CY AUG, 2004 CL Prague, CZECH REPUBLIC ID GRAFT-VERSUS-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; AUTOLOGOUS TRANSPLANTATION; HOST-DISEASE; HEMATOLOGIC MALIGNANCIES; HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA; BLOOD; ENGRAFTMENT AB Purpose Several studies have investigated the feasibility of allogeneic hematopoietic cell transplantations (HCTs) after reduced-intensity conditioning in patients who experienced relapse after myeloablative HCT. Although most studies showed relatively low nonrelapse mortality (NRM) rates and encouraging short-term results, it has yet to be defined which patients would benefit most from these approaches. Patients and Methods We analyzed data from 147 patients with hematologic malignancies who experienced treatment failure with conventional autologous (n = 135), allogeneic (n = 10), or syngeneic (n = 2) HCT and were treated with HLA-matched related (n = 62) or unrelated (n = 85) grafts after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Results Three-year probabilities of NRM, relapse, and overall survival were 32%, 48%, and 27%, respectively, for related recipients, and 28%, 44%, and 44%, respectively, for unrelated recipients. The best outcomes were observed in patients with non-Hodgkin's lymphoma, whereas patients with multiple myeloma and Hodgkin's disease had worse outcomes as a result of high incidences of relapse and progression. Being in partial remission (PR) or complete remission (CR) at HCT (P = .002) and developing chronic graft-versus-host disease (GVHD; P = .03) resulted in lower risks of relapse and progression. Factors associated with better overall survival were PR or CR (P = .01) and lack of comorbidity (P = .03) at HCT and absence of acute GVHD after HCT (P = .06). Conclusion Encouraging outcomes were seen with allogeneic HCT after nonmyeloablative conditioning in selected patients who had experienced relapse after a high-dose HCT, particularly in patients with non-Hodgkin's lymphoma. Results with unrelated grafts were comparable with results with related grafts. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Sch Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Stanford Univ, Stanford, CA 94305 USA. City Hope Comprehens Canc Ctr, Duarte, CA USA. Rocky Mt Canc Ctr, Denver, CO USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Utah, Salt Lake City, UT USA. Baylor Univ, Dallas, TX USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Liege, Liege, Belgium. Univ Leipzig, D-7010 Leipzig, Germany. Univ Turin, Turin, Italy. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM bsandmai@fhcrc.org FU NCI NIH HHS [CA15704, CA92058, CA78902, P01 CA078902, CA49605, CA18029]; NHLBI NIH HHS [HL36444] NR 44 TC 66 Z9 67 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2006 VL 24 IS 25 BP 4150 EP 4157 DI 10.1200/JCO.2006.06.9914 PG 8 WC Oncology SC Oncology GA 081LV UT WOS:000240320000018 PM 16896000 ER PT J AU D'Amico, AV Loffredo, M Renshaw, AA Loffredo, B Chen, MH AF D'Amico, Anthony V. Loffredo, Marian Renshaw, Andrew A. Loffredo, Brittany Chen, Ming-Hui TI Six-month androgen suppression plus radiation therapy compared with radiation therapy alone for men with prostate cancer and a rapidly increasing pretreatment prostate-specific antigen level SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; COMPETING RISK; DOUBLING TIME; PSA VELOCITY; FAILURE; MORTALITY AB Purpose We evaluated whether treatment with 6 months of androgen-suppression therapy (AST) and radiation therapy (RT) compared with RT was associated with the time to prostate-specific antigen (PSA) recurrence, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) in men with a pretreatment PSA velocity more than 2 ng/mL/yr. Patients and Methods The study cohort comprised 241 men with clinically localized or locally advanced prostate cancer treated with RT and AST or RT from 1989 to 2002. Cox regression and Gray's formulation were used to assess whether treatment was associated significantly with the time to PSA recurrence or ACM and PCSM, respectively, adjusting for known prognostic factors. Results Despite the significantly longer median follow-up, younger age at diagnosis, higher proportion of Gleason score 7 to 10, and advanced T-category cancers, significantly lower estimates of PSA recurrence (P < .001), PCSM (P = .007), and ACM (P < .001) were observed in men who were treated using RT and AST compared with BT. Treatment with BT and AST compared with RT was associated with a longer time to PSA recurrence (adjusted hazard ratio [HR], 0.22; 95% CI, 0.14 to 0.35; P < .001), PCSM (HR, 0.23, 95% CI, 0.09 to 0.64; P = .005), and ACM (HR, 0.30; 95% CI, 0.16 to 0.58; P < .001). Conclusion Treatment using 6 months of AST and RT compared with BT in men with a pretreatment PSA velocity greater than 2 ng/mL/yr was associated with a longer time to PSA recurrence, PCSM, and ACM. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 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@iroc.harvard.edu NR 24 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2006 VL 24 IS 25 BP 4190 EP 4195 DI 10.1200/JCO.2006.06.8239 PG 6 WC Oncology SC Oncology GA 081LV UT WOS:000240320000024 PM 16943536 ER PT J AU Hussein, MR Hassan, HI AF Hussein, M. R. Hassan, H. I. TI Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID CANCER-CELLS; GRANZYME-B; T-CELLS; LYMPHOCYTES; EXPRESSION; MUTATIONS; STAGE; RISK; LUNG; P53 AB Background: Mammary carcinogenesis is a multistep process entailing the transition from normal breast to benign proliferative breast disease (ductal hyperplasia) to ductal carcinoma in situ to infiltrating ductal carcinoma. Hypothesis: These transitions are associated with changes in the mononuclear inflammatory cell infiltrate. Materials and methods: A total of 53 mastectomy specimens of normal breast, benign proliferative breast disease, ductal carcinoma in situ and infiltrating ductal carcinoma were evaluated for mononuclear inflammatory cell infiltrate by using immunohistological methods and monoclonal antibodies including CD20, CD68, CD3 and granzyme B, histiocytes, T cells and cytotoxic T cells. Results: Transitions from normal breast to the subsequent tissue with lesions (normal skin v benign proliferative breast disease v ductal carcinoma in situ v infiltrating ductal carcinoma) were associated with significantly (p < 0.01) increased mean (SD) density of mononuclear inflammatory cell infiltrate at the parenchyma (3.2 (1.0) v 26.4 (7.8) v 33.6 (7.9) v 39.1 (4.7) for CD20+ B cells; 2.8 (1.0) v 81.5 (14.0) v 84.0 (14.9) v103.7 (3.9) for CD3; 1.3 (2.0) v 3.8 (4.0) v 12.7 (23) v 22.1 (25.0) for CD68+ macrophages; 2.0 (1.0) v 58.3 (5.0) v 60.0 (10.0) v 74.1 (28.0) for granzyme B+ cytotoxic T cells) and at the stroma (0.7 (1.0) v 3.0 (5.0) v 13.3 (20) v 16.7 (30.0) for CD20+ B cells; 1.0 (2.06) v 4.0 (2.5) v 16.7 (5.0) v 21.7 (15) for CD68+ macrophages; 1.4 (0.6) v 4.2 (1.2) v 46.6 (16.7) v 77.0 (5.0) for CD3+ cells and 0 (0) v 0.5 (1.0) v 0.7 (1.0) v 0.7 (1.0) for granzyme B+ cytotoxic T cells). Conclusions: The increased mononuclear inflammatory cell infiltrate during mammary carcinogenesis may reflect non-specific or specific immunological processes. C1 Assir Cent Hosp, Dept Histopathol, Abha, Saudi Arabia. Assiut Univ, Dept Pathol, Assiut Univ Hosp, Fac Med, Assiut, Egypt. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Madison, WI 53705 USA. RP Hussein, MR (reprint author), Assir Cent Hosp, Dept Histopathol, Abha, Saudi Arabia. EM mrh17@swissinfo.org NR 23 TC 38 Z9 40 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD SEP PY 2006 VL 59 IS 9 BP 972 EP 977 DI 10.1136/jcp.2005.031252 PG 6 WC Pathology SC Pathology GA 077PQ UT WOS:000240042500014 PM 16935972 ER PT J AU Lopez, NJ Socransky, SS Da Silva, I Japlit, MR Haffajee, AD AF Lopez, Nestor J. Socransky, Sigmund S. Da Silva, Isabel Japlit, Michele R. Haffajee, Anne D. TI Effects of metronidazole plus amoxicillin as the only therapy on the microbiological and clinical parameters of untreated chronic periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE antibiotics; clinical trials; controlled; metronidazole-amoxicillin/therapeutic use; microbiology; periodontal diseases; scaling and root planing; subgingival microbiota ID PROFESSIONAL PLAQUE REMOVAL; SYSTEMIC METRONIDAZOLE; ADULT PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; ANTIBIOTIC-RESISTANCE; NONSURGICAL TREATMENT; BRAZILIAN POPULATION; SUBGINGIVAL PLAQUE; PATIENT COMPLIANCE AB Aim: To determine the effect of metronidazole plus amoxicillin (M+A) as the sole therapy, on the subgingival microbiota of chronic periodontitis. Material and Methods: Twenty-two patients with untreated chronic periodontitis were randomly assigned to a group that received M+A for 7 days, or to a group receiving scaling and root planing (SRP) and two placebos. Clinical measurements including sites with plaque, bleeding on probing (BOP), probing depth (PD) and attachment level (AL) were made at baseline, 3, 6, 9 and 12 months. Subgingival plaque samples were taken from all teeth at baseline 3, 6, 9 and 12 months for the counts of 40 subgingival species using checkerboard DNA-DNA hybridization. Results: Mean PD was reduced from 2.80 +/- 0.45 at baseline to 1.95 +/- 0.05 at 12 months (P < 0.001) and from 2.39 +/- 0.41 to 1.95 +/- 0.10 (P < 0.001) in the M+A- and SRP-treated patients, respectively. Corresponding values for relative mean AL were 10.07 +/- 1.30-9.77 +/- 0.34 (P < 0.001) and 9.94 +/- 0.28-9.77 +/- 0.26 (P < 0.001). Percentage of sites exhibiting BOP were 40.6 +/- 18.3-14.0 +/- 1.4 (P < 0.001), and 38.5 +/- 5.1-19.0 +/- 2.8 (P < 0.001) in the M+A and SRP groups, respectively. Mean total DNA probe counts and counts of the majority of the 40 test species were significantly reduced over time in both groups, with no significant differences detected at any time point between groups. At 12 months many of the species were still present at significantly lowered levels compared with their baseline counts in both groups. Conclusions: Changes in clinical and microbiological parameters were similar after receiving systemically administered M+A as the sole therapy or after receiving SRP only. C1 Univ Chile, Fac Dent, Dept Conservat Dent, Santiago, Chile. Forsyth Dent Inst, Dept Periodontol, Boston, MA USA. RP Lopez, NJ (reprint author), Jose Antonio Soffia 2747,Of 603 Santiago, Santiago 7510008, Chile. EM nlopez@interactiva.cl NR 62 TC 44 Z9 47 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 2006 VL 33 IS 9 BP 648 EP 660 DI 10.1111/j.1600-051X.2006.00957.x PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 069NE UT WOS:000239453800007 PM 16856904 ER PT J AU Trivedi, MH Fava, M Marangell, LB Osser, DN Shelton, RC AF Trivedi, Madhukar H. Fava, Maurizio Marangell, Lauren B. Osser, David N. Shelton, Richard C. TI Use of treatment algorithms for depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID MAJOR DEPRESSION; DOUBLE-BLIND; BUPROPION-SR; ASTERISK-D; AUGMENTATION; FLUOXETINE; DISORDER; FAILURE; LITHIUM; TRIAL C1 Univ Texas, SW Med Ctr, Dept Psychiat, Mood Disorders Program & Clin, Dallas, TX 75235 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Baylor Coll Med, Dept Psychiat, Mood Disorders Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Vanderbilt Univ Sch Med, Dept Psychiat, Nashville, TN USA. RP Trivedi, MH (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, Mood Disorders Program & Clin, Dallas, TX 75235 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2006 VL 67 IS 9 BP 1458 EP 1465 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 095WN UT WOS:000241339100019 PM 17017835 ER PT J AU Howard, I Turner, R Olkin, R Mohr, DC AF Howard, Isa Turner, Rebecca Olkin, Rhoda Mohr, David C. TI Therapeutic alliance mediates the relationship between interpersonal problems and depression outcome in a cohort of multiple sclerosis patients SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE working alliance; interpersonal problems; multiple sclerosis; depression ID WORKING ALLIANCE; EXPERIENTIAL THERAPY; RATING-SCALE; INVENTORY; PSYCHOTHERAPY; METAANALYSIS; VALIDITY; RUPTURES AB The relationship among therapeutic alliance, psychotherapy outcomes, and interpersonal problems was examined. The present study hypothesized therapeutic alliance would mediate the relationship between interpersonal functioning and outcome among patients with multiple sclerosis entering psychotherapy for depression. Nineteen clients received 16 weeks of individual cognitive-behavioral therapy (CBT) for depression as described by D. C. Mohr, A. C. Boudewyn, D. E. Goodkin, A. Bostrom, and L. Epstein (2001). Participants completed the Beck Depression Inventory (BDI: Beck, Ward, Mendelson, Mock, & Erbaugh, 1961), the Inventory of Interpersonal Problems-Circumplex (IIP-C: Alden, Wiggins, & Pincus, 1990), and the Working Alliance Inventory-Client Form (WAI-C; Horvath & Greenberg, 1989). The IIP-C significantly predicted Week 16 BDI and the WAI-C at 4 weeks. When controlling for the WAI-C, the relationship between the IIP-C and BDI was no longer significant, supporting the mediational hypothesis. (c) 2006 Wiley Periodicals, Inc. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94131 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Howard, I (reprint author), San Francisco Vet Affairs Med Ctr, 4150 Clement St,116-S, San Francisco, CA 94131 USA. EM Isa.Howard@va.gov FU CSR NIH HHS [RG2719 A1/2] NR 32 TC 17 Z9 18 U1 2 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2006 VL 62 IS 9 BP 1197 EP 1204 DI 10.1002/jclp.20274 PG 8 WC Psychology, Clinical SC Psychology GA 076BO UT WOS:000239932200011 PM 16810663 ER PT J AU Guenther, FH AF Guenther, Frank H. TI Cortical interactions underlying the production of speech sounds SO JOURNAL OF COMMUNICATION DISORDERS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Speech-Language-Hearing-Association CY NOV 18-20, 2005 CL San Diego, CA SP Amer Speech Language Hearing Assoc ID SUPERIOR TEMPORAL GYRUS; VERTICAL-BAR PRODUCTION; HUMAN AUDITORY-CORTEX; NEURAL-NETWORK MODEL; NEURONAL-ACTIVITY; RESPONSES; SPEAKERS; DISCRIMINATION; ARTICULATION; DISTINCTNESS AB Speech production involves the integration of auditory, somatosensory, and motor information in the brain. This article describes a model of speech motor control in which a feedforward control system, involving premotor and primary motor cortex and the cerebellum, works in concert with auditory and somatosensory feedback control systems that involve both sensory and motor cortical areas. New speech sounds are learned by first storing an auditory target for the sound, then using the auditory feedback control system to control production of the sound in early repetitions. Repeated production of the sound leads to tuning of feedforward commands which eventually supplant the feedback-based control signals. Although parts of the model remain speculative, it accounts for a wide range of kinematic, acoustic, and neuroimaging data collected during speech production and provides a framework for investigating communication disorders that involve malfunction of the cerebral cortex and interconnected subcortical structures. Learning outcomes: Readers will be able to: (1) describe several types of learning that occur in the sensory-motor system during babbling and early speech, (2) identify three neural control subsystems involved in speech production, (3) identify regions of the brain involved in monitoring auditory and somatosensory feedback during speech production, and (4) identify regions of the brain involved in feedforward control of speech. (c) 2006 Elsevier Inc. All rights reserved. C1 Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Guenther, FH (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM guenther@cns.bu.edu FU NIDCD NIH HHS [R01 DC02852] NR 52 TC 226 Z9 231 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0021-9924 J9 J COMMUN DISORD JI J. Commun. Disord. PD SEP-OCT PY 2006 VL 39 IS 5 BP 350 EP 365 DI 10.1016/j.jcomdis.2006.06.013 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 105LE UT WOS:000242030600003 PM 16887139 ER PT J AU Setty, BN Sahani, DV Ouellette-Piazzo, K Hahn, PF Shepard, JAO AF Setty, Bindu N. Sahani, Dushyant V. Ouellette-Piazzo, Kathy Hahn, Peter F. Shepard, Jo-Anne O. TI Comparison of enhancement, image quality, cost, and adverse reactions using 2 different contrast medium concentrations for routine chest CT on 16-slice MDCT SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article ID THORACIC SPIRAL CT; DETECTOR-ROW CT; VASCULAR OPACIFICATION; IODINE CONCENTRATION; HEPATIC ENHANCEMENT; POWER INJECTOR; SALINE FLUSH; HELICAL CT; REDUCTION; ANGIOGRAPHY AB Objective: To evaluate the degree of enhancement and image quality of chest computed tomographic (CT) examinations on 16-slice multidetector CT using low-concentration [300 milligrams of iodine per milliliter (mg I/mL)] and high-concentration (370 mg I/mL) contrast media; to assess the impact on cost and adverse reactions of the use of high-iodine concentration contrast medium. Materials and Methods: A total of 100 patients scheduled for routine chest CT examinations were administered nonionic contrast medium of 2 strengths: low-iodine concentration contrast medium (300 mg I/mL) [group A: n = 50; male-female ratio, 28:22; mean age, 58.4 years] and high-iodine concentration contrast medium (370 mg I/mL) (group B: n = 50; male-female ratio, 18:32; mean age, 57.6 years) with a constant amount of iodine (400 mg) injected per kilogram of body weight. Contrast media were injected using a dual injector at 2.5 mL/s followed by a 30-mL saline at 2.5 mL/s. The degree of enhancement was quantified by measuring Hounsfield unit values in different arteries and veins and was also rated on a 5-point scale for qualitative assessment. We also evaluated perivenous contrast-related artifacts. The data were compared using Mann-Whitney U test for both qualitative and quantitative enhancement ratings. A P value of less than 0.05 was considered statistically significant. The P value was adjusted using Bonferroni correction for statistical significance when multiple comparisons were performed. The difference in cost and the incidence of adverse reactions in both groups were calculated. Results: The mean enhancement values in group B were significantly greater (P < 0.05) than those in group A. The mean Hounsfield units and standard deviation in groups A and B were aorta = 153 +/- 4, 216 +/- 20; pulmonary artery = 147 +/- 10, 208 +/- 20; superior vena cava = 155 +/- 27, 299 +/- 72; and pulmonary vein = 134 +/- 10, 215 +/- 30, respectively. The mean enhancement on a 5-point scale was greater in group B (4.2) than in group A (3.3) (P < 0.01). No significant difference between groups in perivenous artifacts was seen. Up to 5.5% savings in cost resulted from the use of a higher concentration of iodine, with no increase in adverse reactions. Conclusions: Use of higher-concentration contrast media provides a higher degree of contrast enhancement and image quality for a routine chest CT on a 16-slice multidetector CT. It also contributes to considerable cost savings with no increased risk of adverse reactions compared with low-concentration contrast media. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Chest, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 18 TC 33 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2006 VL 30 IS 5 BP 818 EP 822 DI 10.1097/01.rct.0000229999.30897.3b PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 084KD UT WOS:000240530900021 PM 16954936 ER PT J AU Margolis, HC Beniash, E Fowler, CE AF Margolis, H. C. Beniash, E. Fowler, C. E. TI Role of macromolecular assembly of enamel matrix proteins in enamel formation SO JOURNAL OF DENTAL RESEARCH LA English DT Review DE amelogenin; amelogenesis; enamel; matrix; proteins; self-assembly ID DYNAMIC LIGHT-SCATTERING; DEVELOPING BOVINE ENAMEL; INTRACRYSTALLINE BIOMINERALIZATION PROTEIN; ELECTRON-MICROSCOPIC TOMOGRAPHY; LINKED AMELOGENESIS IMPERFECTA; DEVELOPING DENTAL ENAMEL; IN-OIL MICROEMULSIONS; PORCINE TOOTH GERMS; X-RAY DIFFRACTION; OCTACALCIUM PHOSPHATE AB Unlike other mineralized tissues, mature dental enamel is primarily (> 95% by weight) composed of apatitic crystals and has a unique hierarchical structure. Due to its high mineral content and organized structure, enamel has exceptional functional properties and is the hardest substance in the human body. Enamel formation (amelogenesis) is the result of highly orchestrated extracellular processes that regulate the nucleation, growth, and organization of forming mineral crystals. However, major aspects of the mechanism of enamel formation are not well-understood, although substantial evidence suggests that protein-protein and protein-mineral interactions play crucial roles in this process. The purpose of this review is a critical evaluation of the present state of knowledge regarding the potential role of the assembly of enamel matrix proteins in the regulation of crystal growth and the structural organization of the resulting enamel tissue. This review primarily focuses on the structure and function of amelogenin, the predominant enamel matrix protein. This review also provides a brief description of novel in vitro approaches that have used synthetic macromolecules (i.e., surfactants and polymers) to regulate the formation of hierarchical inorganic (composite) structures in a fashion analogous to that believed to take place in biological systems, such as enamel. Accordingly, this review illustrates the potential for developing bio-inspired approaches to mineralized tissue repair and regeneration. In conclusion, the authors present a hypothesis, based on the evidence presented, that the full-length amelogenin uniquely regulates proper enamel formation through a process of cooperative mineralization, and not as a pre-formed matrix. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. GlaxoSmithKline Inc, Weybridge, Surrey, England. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM hmargolis@forsyth.org FU NIDCR NIH HHS [DE-013237, DE-016376, DE016703, P01 DE013237] NR 185 TC 164 Z9 166 U1 5 U2 40 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2006 VL 85 IS 9 BP 775 EP 793 PG 19 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 077EG UT WOS:000240010000002 PM 16931858 ER PT J AU McLellan, DL Kaufman, NJ AF McLellan, Deborah L. Kaufman, Nancy J. TI Examining the effects of tobacco control policy on low socioeconomic status women and girls: an initiative of the Tobacco Research Network on Disparities (TReND) SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Editorial Material AB This commentary focuses on the convening of a national meeting of experts to develop a research agenda for investigating the effects of tobacco control policies on low socioeconomic women and girls. C1 Dana Farber Canc Inst, Ctr Community Based Res, Unit L, Jamaica Plain, MA 02130 USA. Aurora Hlth Care, Milwaukee, WI USA. RP McLellan, DL (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Unit L, 196 Chestnut Ave, Jamaica Plain, MA 02130 USA. EM Deborah_mclellan@comcast.net NR 7 TC 5 Z9 5 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD SEP PY 2006 VL 60 SU 2 BP 5 EP 6 DI 10.1136/jech.2006.052407 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 079VQ UT WOS:000240206400003 PM 17708004 ER PT J AU Balbach, ED Herzberg, A Barbeau, EM AF Balbach, Edith D. Herzberg, Abby Barbeau, Elizabeth M. TI Political coalitions and working, women: how the tobacco industry built a relationship with the Coalition of Labor Union Women SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article AB Objectives: To assess how the tobacco industry established a political relationship with the Coalition of Labor Union Women (CLUW) and to learn from this example how tobacco control advocates can work more effectively with organisations with which working class women are affiliated. Methods: The study reviewed tobacco industry documents to determine Tobacco Institute strategy, using the CLUW News and other published material to corroborate our findings. Results: The Tobacco Institute was effective at framing excise tax and smokefree worksite issues in a way that facilitated CLUW's support of industry positions on these issues. The Tobacco Institute was also willing to reciprocate by providing financial and other kinds of support to CLUW. Conclusions: While tobacco control missed an opportunity to partner with CLUW on smokefree worksites and excise taxes in the 1980s and 1990s, tobacco control can also use issue framing and reciprocity to form coalitions with organisations representing the interests of working women. C1 Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Balbach, ED (reprint author), 112 Packard Ave, Medford, MA 02155 USA. EM edith.balbach@tufts.edu FU NCI NIH HHS [R01 CA095964] NR 37 TC 19 Z9 19 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD SEP PY 2006 VL 60 SU 2 BP 27 EP 32 DI 10.1136/jech.2006.046276 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 079VQ UT WOS:000240206400007 PM 17708008 ER PT J AU Sullivan, AM Lakoma, MD Billings, JA Peters, AS Block, SD AF Sullivan, Amy M. Lakoma, Matthew D. Billings, J. Andrew Peters, Antoinette S. Block, Susan D. CA PCEP Core Faculty TI Creating enduring change - Demonstrating the long-term impact of a faculty development program in palliative care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE palliative care; medical education; nursing education; faculty development program ID CONTINUING MEDICAL-EDUCATION; OF-LIFE CARE; COMPETENCE; PHYSICIAN; INTERVENTIONS; 21ST-CENTURY; PERFORMANCE; TEACHERS; EFFICACY; OUTCOMES AB BACKGROUND: Improved educational and evaluation methods are needed in continuing professional development programs. OBJECTIVE: To evaluate the long-term impact of a faculty development program in palliative care education and practice. DESIGN: Longitudinal self-report surveys administered from April 2000 to April 2005. PARTICIPANTS: Physician and nurse educators from North America and Europe. All program graduates in = 156) were invited to participate. INTERVENTION. Two-week program offered annually (2000 to 2003) with 2 on-site sessions and 6-month distance-learning period. Learner-centered training addressed teaching methods, clinical skill development, and organizational and professional development. MEASURES: Self-administered survey items assessing behaviors and attitudes related to palliative care teaching, clinical care, and organizational and professional development at pre-, postprogram, and long-term (6, 12. or 18 months) follow-up. RESULTS: Response rates: 96% in = 149) preprogram, 73% in = 114) follow-up. Participants reported increases in: time spent in palliative care practice (38% preprogram, 47% follow-up, P <.01); use of learner-centered teaching approaches (sum of 8 approaches used "a lot": preprogram 0.7 +/- 1.1, follow-up 3.1 +/- 2.0, P <.000 1); and palliative care topics taught (sum of 11 topics taught "a lot": preprogram 1. 6 2.0, follow-up 4.9 +/- 2.9. P <.0001). Reported clinical practices in psychosocial dimensions of care improved (e.g., assessed psychosocial needs of patient who most recently died: 68% preprogram, 85% follow-up, P=.01). Nearly all (90%) reported launching palliative care initiatives, and attributed their success to program participation. Respondents reported major improvements in confidence, commitment to palliative care, and enthusiasm for teaching. Eighty-two percent reported the experience as "transformative." CONCLUSIONS: This evidence of enduring change provides support for the potential of this educational model to have measurable impact on practices and professional development of physician and nurse educators. C1 Dana Farber Canc Inst, Boston, MA 01984 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sullivan, AM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 01984 USA. EM amy_sullivan@dfci.harvard.edu NR 58 TC 30 Z9 31 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2006 VL 21 IS 9 BP 907 EP 914 DI 10.1111/j.1525-1497.2006.00486.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 074DG UT WOS:000239792300002 PM 16918733 ER PT J AU Nelson, KM AF Nelson, Karin M. TI The burden of obesity among a national probability sample of veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Centers-for-Disease-Control Diabetes and Obesity Conference CY MAY 16-19, 2006 CL Denver, CO SP Ctr Dis Control DE veterans; obesity ID HEALTH-CARE-SYSTEM; BODY-MASS INDEX; QUALITY-OF-LIFE; BARIATRIC SURGERY; US ADULTS; DISEASE BURDEN; WEIGHT-LOSS; FOLLOW-UP; OVERWEIGHT; PREVALENCE AB BACKGROUND: Few national data exist about the prevalence of obesity and the resulting health burden among veterans. METHODS: We analyzed data from the 2003 Behavioral Risk Factor Surveillance System (n=242,362) to compare rates of obesity among veterans who do and do not utilize the VA, compared with nonveterans. We used bivariate analyses to describe the association of obesity with lifestyle factors. disability, and comorbid disease, and multivariate analysis to assess the independent association of obesity with VA care. RESULTS: Veterans who use the VA for health care have the highest rates of obesity compared with veterans who do not use the VA and nonveterans (27.7% vs 23.9% vs 22.8%, P <.00 1). Only 27.8% of veterans who receive health care at the VA are of normal weight (vs 42.6% of the general population, P <.001), 44.5% are overweight, 19.9% have class I obesity. 6% have class II obesity, and 1.8% are morbidly obese (an estimated 82.950 individuals). Obese veterans who utilize the VA for services have higher rates of hypertension (65.8%) and diabetes (31.3%), are less likely to follow diet and exercise guidelines, and more likely to report poor health and disability than their normal-weight counterparts. CONCLUSIONS: Veterans who receive care at the VA have higher rates of overweight and obesity than the general population. At present, less than half of VA medical centers have weight management programs. As the largest integrated U.S. health system, the VA has a unique opportunity to respond to the epidemic of obesity. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Nelson, KM (reprint author), 1660 S Columbian Way S-111 GIMC, Seattle, WA 98108 USA. EM Karin.Nelson@va.gov NR 43 TC 71 Z9 71 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2006 VL 21 IS 9 BP 915 EP 919 DI 10.1111/j.1525-1497.2006.00526.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 074DG UT WOS:000239792300003 PM 16918734 ER PT J AU McCormick, KA Cochran, NE Back, AL Merrill, JO Williams, EC Bradley, KA AF McCormick, Kinsey A. Cochran, Nancy E. Back, Anthony L. Merrill, Joseph O. Williams, Emily C. Bradley, Katharine A. TI How primary care providers talk to patients about alcohol - A qualitative study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE alcohol drinking; primary care; communication; physician-patient relations ID PRIMARY-HEALTH-CARE; BRIEF PHYSICIAN ADVICE; BEHAVIORAL-COUNSELING INTERVENTIONS; RANDOMIZED CONTROLLED TRIAL; BENEFIT-COST-ANALYSIS; GENERAL-PRACTITIONERS; PROBLEM DRINKING; PROBLEM DRINKERS; CONSUMPTION; ATTITUDES AB BACKGROUND: Alcohol misuse is a common and well-documented source of morbidity and mortality. Brief primary care alcohol counseling has been shown to benefit patients with alcohol misuse. OBJECTIVE: To describe alcohol-related discussions between primary care providers and patients who screened positive for alcohol misuse. DESIGN., An exploratory, qualitative analysis of audiotaped primary care visits containing discussions of alcohol use. PARTICIPANTS: Participants were 29 male outpatients at a Veterans Affairs (VA) General Internal Medicine Clinic who screened positive for alcohol misuse and their 14 primary care providers, all of whom were participating in a larger quality improvement trial. MEASUREMENTS: Audiotaped visits with any alcohol-related discussion were transcribed and coded using grounded theory and conversation analysis, both qualitative research techniques. RESULTS: Three themes were identified: (1) patients disclosed information regarding their alcohol use, but providers often did not explore these disclosures; (2) advice about alcohol use was typically vague and/or tentative in contrast to smoking-related advice, which was more common and usually more clear and firm; and (3) discomfort on the part of the provider was evident during alcohol-related discussions. LIMITATIONS: Generalizability of findings from this single-site VA study is unknown. CONCLUSION: Findings from this single site study suggest that provider discomfort and avoidance are important barriers to evidence-based brief alcohol counseling. Further investigation into current alcohol counseling practices is needed to determine whether these patterns extend to other primary care settings, and to inform future educational efforts. C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. White River Junct VA Hosp, White River Jct, VT USA. Dartmouth Coll Sch Med, Dept Med & Community & Family Med, Hanover, NH USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP McCormick, KA (reprint author), VA Puget Sound Hlth Serv Res & Dev 152, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM kamc@u.washington.edu FU NIAAA NIH HHS [K23 AA000313, K23AA00313] NR 47 TC 55 Z9 56 U1 4 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2006 VL 21 IS 9 BP 966 EP 972 DI 10.1111/j.1525-1497.2006.00490.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 074DG UT WOS:000239792300012 PM 16918743 ER PT J AU Atlas, SJ Chang, YC Lasko, TA Chueh, HC Grant, RW Barry, MJ AF Atlas, Steven J. Chang, Yuchiao Lasko, Thomas A. Chueh, Henry C. Grant, Richard W. Barry, Michael J. TI Is this "My" Patient? Development and validation of a predictive model to link patients to primary care providers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med DE primary health care; health services research; quality of care; patient roster; provider denominator ID HEALTH-CARE; UNITED-STATES; QUALITY; CONTINUITY; PHYSICIANS AB BACKGROUND: Evaluating the quality of care provided by individual primary care physicians (PCPs) may be limited by failing to know which patients the PCP feels personally responsible for. OBJECTIVE: To develop and validate a model for linking patients to specific PCps. DESIGN. Retrospective convenience sample. PARTICIPANTS: Eighteen PCPs from 10 practice sites within an academic adult primary care network. MEASUREMENTS: Each PCP reviewed the records for all outpatients seen over the preceding 3 years (16,435 patients reviewed) and designated each patient as "My Patient" or "Not My Patient Using this reference standard, we developed an algorithm with logistic regression modeling to predict "My Patient" using development and validation subsets drawn from the same patient set. Quality of care was then assessed by "My Patient" or "Not My Patient" designation by analyzing cancer screening test rates. RESULTS: Overall, PCPs designated 11,226 patients (68.3%, range per provider 15% to 93%) to be "My Patient." The model accurately categorized patients in development and validation subsets (combined sensitivity 80.4%, specificity 93.7%, and positive predictive value 96.5%). To achieve positive predictive values of > 90% for individual PCPs, the model excluded 19.6% of PCP "My Patients" (range 5.5% to 75.3%). Cancer screening rates were higher among model-predicted "My Patients." CONCLUSIONS: Nearly one-third of patients seen were considered "Not My Patient" by the PCP, although this proportion varied widely. We developed and validated a simple model to link specific patients and PCPs. Such efforts may help effectively target interventions to improve primary care quality. C1 Harvard Univ, Div Gen Med, Med Serv, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02115 USA. RP Atlas, SJ (reprint author), Harvard Univ, Div Gen Med, Med Serv, Massachusetts Gen Hosp,Med Sch, 50 Staniford St, Boston, MA 02114 USA. EM sattas@partners.org OI Grant, Richard/0000-0002-6164-8025 NR 19 TC 27 Z9 27 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2006 VL 21 IS 9 BP 973 EP 978 DI 10.1111/j.1525-1497.2006.00509.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 074DG UT WOS:000239792300013 PM 16918744 ER PT J AU Fung, CH AF Fung, Constance H. TI Computerized condition-specific templates for improving care of geriatric syndromes in a primary care setting SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID VULNERABLE ELDERS; INTERVENTIONS; INCONTINENCE; COMMUNITY; QUALITY; HEALTH; TRIAL; FALLS AB INTRODUCTION. As the U.S. population ages, primary care clinicians (PCCs) will encounter more patients with geriatric syndromes, such as urinary incontinence (Ul) and falls. Yet, current evidence suggests that care of these conditions does not meet expected standards and that PCCs would benefit from tools to improve care of these conditions. Little is known about the role of computerized condition-specific templates for improving care of geriatric syndromes. AIM: We sought to develop and assess the usefulness of condition-specific computerized templates in a primary care setting. SETTING: A large academic Veterans Affairs medical center. PROGRAM DESCRIPTION: We developed and tested the usefulness of 2 condition-specific computerized templates (UI and falls) that could be added on to an existing electronic health record system. PROGRAM EVALUATION., Semistructured interviews were used to identify barriers to use of computerized templates. Usefulness and usability were assessed through a randomized-controlled trial involving standardized patients. DISCUSSION: Use of condition-specific templates resulted in improved history and physical exam assessment for both Ul and falls (P <.05). Our computerized, condition-specific templates are a promising method for improving care of geriatric conditions in a primary care setting. but require improvement in usability before widespread implementation. C1 Univ Calif Los Angeles, RAND Corp, David Geffen Sch Med,Div Gen Internal Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Fung, CH (reprint author), 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM cfung@rand.org FU NIA NIH HHS [P60 AG10415, P60 AG010415] NR 26 TC 11 Z9 11 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2006 VL 21 IS 9 BP 989 EP 994 DI 10.1111/j.1525-1497.2006.00522.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 074DG UT WOS:000239792300016 PM 16918747 ER PT J AU Siminoff, LA Burant, CJ Ibrahim, SA AF Siminoff, Laura A. Burant, Christopher J. Ibrahim, Said A. TI Racial disparities in preferences and perceptions regarding organ donation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE decision making; disparities; minorities; organ donation; attitudes; African Americans ID AFRICAN-AMERICANS; UNITED-STATES; PROCUREMENT; ATTITUDES; BLACKS; POLICY; RACE AB OBJECTIVES: To identify reasons for lower organ donation rates by African Americans, we examined knowledge and attitudes about brain death, donation, and transplantation and trust in the health care system. METHODS: Data were collected from 1,283 subjects in Ohio using a random digit dial telephone survey. Items were developed based on focus group results. Willingness-to-donate indicators included a signed donor card and willingness to donate one's own and a loved one's organs. RESULTS: Compared with whites, African-Americans had lower rates of signing a donor card (39.1% vs 64.9%, P <.001), and willingness to donate their own organs (72.6% vs 88.3%, P <.0011 or a loved one's organs (53.0%vs 66.2%, P <.001). African Americans had lower scores on the Trust in the Health Care System scale (mean scores +/- SD, 9.43 +/- 3.05 vs 9.93 +/- 2.88, P <.01) and were more likely to agree that "if doctors know I am an organ donor, they won't try to save my life" (38.6% vs 25.9%, P <.001), the rich or famous are more likely to get a transplant (81.9% vs 75.7%, P <.05), and less likely to agree that doctors can be trusted to pronounce death (68.2% vs 82.9. P <.001). African Americans were also more likely to agree that families should receive money for donating organs (45.6% vs 28.0%, P <.001) and funeral expenses (63.1% vs 46.6%, P <. 001). CONCLUSIONS: African Americans reported greater mistrust in the equity of the donation system and were more favorable about providing tangible benefits to donor families than white respondents. C1 Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Siminoff, LA (reprint author), Case Western Reserve Univ, Sch Med, Dept Bioeth, TA-215,10900 Euclid Ave, Cleveland, OH 44106 USA. EM las5@case.edu RI Siminoff, Laura /H-6277-2012 FU AHRQ HHS [R01 HS010047, R01-HS10047] NR 27 TC 76 Z9 78 U1 0 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2006 VL 21 IS 9 BP 995 EP 1000 DI 10.1111/j.1525-1497.2006.00516.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 074DG UT WOS:000239792300017 PM 16918748 ER PT J AU Breitner, JCS AF Breitner, John C. S. TI Dementia - Epidemiological considerations, nomenclature, and a tacit consensus definition SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE dementia; definition; syndrome; neuropathology; epidemiology ID ALZHEIMERS-DISEASE; CACHE COUNTY; OLD PEOPLE; ONSET; PREVALENCE; AGE; METAANALYSIS; PREDICTS; BRAINS; WOMEN AB Epidemiologic inquiry requires the definition of a "case." Dementia may be defined clinically or alternatively by inference of irreversible brain pathology. Several iterations of the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases have skirted this issue by using criteria that are at once syndromic and neuropathological. The limitations of this compromise are revealed by large discrepancies in case identification when the various published criteria are strictly applied. Despite this problem, neuroepidemiologists have produced convergent estimates of the prevalence and incidence of dementia and its association with risk factors. This progress has reflected the tacit reliance of investigators on a simple definition of dementia as the syndrome of substantial global cognitive decline not attributable to alteration in level of consciousness. Beyond this description, our knowledge of pathology and, ultimately, the etiology of individual cases is extremely variable. Whatever its antecedents, syndromically defined dementia presents a looming public health crisis. C1 Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Geriatr Psychiat, Seattle, WA 98108 USA. RP Breitner, JCS (reprint author), Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jcsb@u.washington.edu NR 31 TC 10 Z9 11 U1 2 U2 7 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 2006 VL 19 IS 3 BP 129 EP 136 DI 10.1177/0891988706291081 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 077HW UT WOS:000240020900003 PM 16880354 ER PT J AU Blacker, D Lovestone, S AF Blacker, Deborah Lovestone, Simon TI Genetics and dementia nosology SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT Meeting on Diagnostic Issues in Dementia - Future of Psychiatric Diagnosis - Refinding the Research Agenda CY SEP 15-17, 2005 CL Geneva, SWITZERLAND SP Amer Psychiat Assoc, US Natl Inst Hlth, World Hlth Org DE dementia; Alzheimer's disease; DSM-V; genetics ID FAMILIAL ALZHEIMERS-DISEASE; MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E GENOTYPE; QUALITY STANDARDS SUBCOMMITTEE; ACADEMY-OF-NEUROLOGY; AGE-AT-ONSET; FRONTOTEMPORAL DEMENTIA; VASCULAR DEMENTIA; APOE GENOTYPE; PATHOLOGICAL DIAGNOSIS AB In preparation for the development of the Diagnostic and Statistical Manual of Mental Disorders (5th ed), the American Psychiatric Association convened workshops reviewing scientific evidence relevant to diagnosis of dementia. One of the domains covered was genetics, which is reviewed here. The following areas are reviewed: genetic data on Alzheimer's disease and other dementias; the impact of nosology on genetic research in terms of its potential to improve diagnostic sensitivity and specificity and to decrease heterogeneity; the impact of genetic research findings on nosology, specific diagnostic criteria, and subtypes; and recommendations and future directions. The focus is on Alzheimer's disease, where more genetic data are available, and other dementias are reviewed more briefly. In addition, a separate section reviews the relationship of genetic findings and mild cognitive impairment, a boundary zone between normal aging and dementia, particularly Alzheimer's disease. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Kings Coll London, MRC, Ctr Neurodegenerat Res, Inst Psychiat, London WC2R 2LS, England. RP Blacker, D (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149-2691,149 13th St, Charlestown, MA 02129 USA. EM blacker@nmr.mgh.harvard.edu RI Lovestone, Simon/E-8725-2010 FU NIA NIH HHS [5 P01 AG4853]; NIMH NIH HHS [5R37 MH60009] NR 65 TC 3 Z9 3 U1 2 U2 3 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 2006 VL 19 IS 3 BP 186 EP 191 DI 10.1177/0891988706291091 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 077HW UT WOS:000240020900010 PM 16880361 ER PT J AU Nazzal, A Lozano-Calderon, S Jupiter, JB Rosenzweig, JS Randolph, MA Lee, SGP AF Nazzal, Adam Lozano-Calderon, Santiago Jupiter, Jesse B. Rosenzweig, Jaime S. Randolph, Mark A. Lee, Sang Gil P. TI A histologic analysis of the effects of stainless steel and titanium implants adjacent to tendons: An experimental rabbit study SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE inflammation; rabbit model; steel; tendon; titanium ID DISTAL RADIUS FRACTURES; INTERNAL-FIXATION; PI-PLATE; ALLOY; COMPLICATIONS; PARTICLES; OSTEOTOMY; MODEL; DOGS; END AB Purpose: The current trend is to treat distal radius fractures with open reduction and internal fixation with either titanium or stainless steel plates. Both provide stable fixation; however, there is minimal evidence concerning the soft-tissue response to these materials. Our objective was to evaluate the response of adjacent extensor tendons to titanium and stainless steel in a rabbit in vivo model and to evaluate the influence of time. Methods: Forty rabbits were divided into 5 groups of 8 rabbits each. Groups I and II had unilateral osteotomy of the distal radius followed by dorsal fixation with titanium and stainless steel plates, respectively. Groups III and IV had fixation with titanium and stainless steel, respectively, but without osteotomy. Group V had surgical dissection without osteotomy or plates. Two animals per group were killed at 1, 4, 12, and 24 weeks. The specimens (distal radius, plate, overlying soft tissue, and extensor tendon) were harvested en bloc for histologic analysis. For interface preservation between implant and tissues the specimens were embedded in methylmethacrylate, sectioned, and stained with hematoxylin-eosin. Results: Histologic analysis showed a fibrous tissue layer formed over both implants between the plate and the overlying extensor tendons in the groups treated with plating independently of the material and the presence or absence of osteotomy. This fibrous layer contained the majority of debris. Metallic particles were not observed in the tendon or muscle substance of any animals; however, they were visualized in the tenosynovium. Hematoxylin-eosin-stained sections of groups I through IV showed proliferative fibroblasts and metallic particles; however, this layer was not observed in group V. Statistical analysis did not show differences between the groups regarding the number of cells or metallic particles. Conclusions: Our results indicate that both implants generated adjacent reactive inflammatory tissue and particulate debris. There was no difference in cell or particle number produced by both materials. There is a statistically significant increase in inflammatory cells with increasing time of implantation. C1 Harvard Univ, Massachusetts Gen Hosp, Hand & Opper Extrm Serv, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Plast Surg, Sch Med, Boston, MA USA. RP Nazzal, A (reprint author), Boston Orthoped & Spine Specialist, 101 Merrimac St,2nd Floor, Boston, MA 02114 USA. EM Anazzal@partners.org NR 22 TC 13 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2006 VL 31A IS 7 BP 1123 EP 1130 DI 10.1016/j.jhsa.2006.03.001 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 081MC UT WOS:000240320700013 PM 16945714 ER PT J AU Pearce, MJ Singer, JL Prigerson, HG AF Pearce, Michelle J. Singer, Jerome L. Prigerson, Holly G. TI Religious coping among caregivers of terminally ill cancer patients - Main effects and psychosocial mediators SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE cancer; caregivers; mediation; mental health; religious coping ID OLDER-ADULTS; LONGITUDINAL CHANGES; ELDERLY-PATIENTS; CHRONICALLY ILL; SELF-EFFICACY; HEALTH-STATUS; STRESS; PEOPLE; INVOLVEMENT; PREDICTORS AB This study investigated the association between religious Coping, mental health and the caring experience, as well as potential explanatory mechanisms, among 162 informal caregivers of terminally ill cancer patients. Regression analyses indicated controlling for socio-demographic variables, more use of positive religious coping strategies was associated with more burden, yet, also more satisfaction. In contrast, more use of negative religious coping strategies was related to more burden, poorer quality of life and less satisfaction, and with an increased likelihood of Major Depressive Disorder and anxiety disorders. In a number of models, negative religious coping was related to outcomes through its relationship with social support, optimism and self-efficacy. Implications for research and healthcare are discussed. C1 Yale Univ, Dept Psychol, New Haven, CT 06520 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pearce, MJ (reprint author), Yale Univ, Dept Psychol, POB 208205, New Haven, CT 06520 USA. EM michelle.pearce@yale.edu FU NCI NIH HHS [CA106370, R01 CA106370]; NIA NIH HHS [P30AG21342]; NIMH NIH HHS [MH56529, MH63892] NR 77 TC 39 Z9 41 U1 1 U2 15 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD SEP PY 2006 VL 11 IS 5 BP 743 EP 759 DI 10.1177/1359105306066629 PG 17 WC Psychology, Clinical SC Psychology GA 087VR UT WOS:000240771400008 PM 16908470 ER PT J AU Best, RG Hysong, SJ Pugh, JA Ghosh, S Moore, FI AF Best, Richard G. Hysong, Sylvia J. Pugh, Jacqueline A. Ghosh, Suvro Moore, Frank I. TI Task overlap among primary care team members: An opportunity for system redesign? SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Article ID MANAGEMENT AB This article presents the results of research(1) on a systematic approach to the assignment of primary care work in the Veterans Health Administration. Based on a functional job analysis protocol, the study identified overlap in the performance of primary care tasks among multiple occupational groups as prima facie evidence of opportunities to reallocate work responsibilities. Results show that registered nurses, physicians, advanced practitioners, and licensed vocational nurses reported performing 60 percent to 97 percent of the same tasks, while clerks and health technicians appeared to be underutilized. The frequency and duration with which occupational groups performed each task were also examined, providing additional evidence to be used in improving clinic efficiency. The management of healthcare personnel can be improved through systematic analysis of the work, the worker, and the work organization and through more informed decisions about the appropriateness of task assignment (or reassignment). This article presents an evidence-based approach to personnel management with important implications for clinic efficiency. The approach can be used to guide strategic planning and staffing decisions by identifying not only who currently does the work but, more importantly, who should be doing the work given the full array of data. C1 Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. Houston Ctr Qual Care & Ultiizat Studies, Houston, TX USA. Baylor Coll Med, Houston, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Sch Publ Hlth, San Antonio, TX USA. RP Best, RG (reprint author), Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. EM rbest@satx.rr.com RI Hysong, Sylvia/B-8420-2008; OI Hysong, Sylvia/0000-0002-9063-5207; Pugh, Jacqueline/0000-0003-4933-141X NR 19 TC 10 Z9 10 U1 0 U2 2 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD SEP-OCT PY 2006 VL 51 IS 5 BP 295 EP 306 PG 12 WC Health Policy & Services SC Health Care Sciences & Services GA 087ZH UT WOS:000240780800005 PM 17039689 ER PT J AU McDivitt, RP AF McDivitt, Robert P. TI Practitioner application SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Editorial Material C1 US Dept Vet Affairs, VA Midwest Hlth Care Network VISN 23, Minneapolis, MN USA. RP McDivitt, RP (reprint author), US Dept Vet Affairs, VA Midwest Hlth Care Network VISN 23, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD SEP-OCT PY 2006 VL 51 IS 5 BP 306 EP 307 PG 2 WC Health Policy & Services SC Health Care Sciences & Services GA 087ZH UT WOS:000240780800006 ER PT J AU Chen, YG Chen, J Osborne, MA Chapman, HD Besra, GS Porcelli, SA Leiter, EH Wilson, SB Serreze, DV AF Chen, Yi-Guang Chen, Jing Osborne, Melissa A. Chapman, Harold D. Besra, Gurdyal S. Porcelli, Steven A. Leiter, Edward H. Wilson, S. Brian Serreze, David V. TI CD38 is required for the peripheral survival of immunotolerogenic CD4(+) invariant NK T cells in nonobese diabetic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYCLIC ADP-RIBOSE; NOD MICE; SURFACE-PROTEINS; B-CELLS; ACTIVATION; INDUCTION; TOLERANCE; RESPONSES; MOUSE; GENE AB T cell-mediated autoimmune type-1 diabetes (T1D) in NOD mice partly results from this strain's numerical and functional defects in invariant NK T (iNKT) cells. T1D is inhibited in NOD mice treated with the iNKT cell superagonist a-galactosylceramide through a process involving enhanced accumulation of immunotolerogenic dendritic cells in pancreatic lymph nodes. Conversely, T1D is accelerated in NOD mice lacking CD38 molecules that play a role in dendritic cell migration to inflamed tissues. Unlike in standard NOD mice, a-galactosylceramide pretreatment did not protect the CD38-deficient stock from T1D induced by an adoptively transferred pancreatic beta cell-autoreactive CD8 T cell clone (AI4). We found that in the absence of CD38, ADP-ribosyltransferase 2 preferentially activates apoptotic deletion of peripheral iNKT cells, especially the CD4(+) subset. Therefore, this study documents a previously unrecognized role for CD38 in maintaining survival of an iNKT cell subset that preferentially contributes to the maintenance of immunological tolerance. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Diabet Res Labs, Cambridge, MA 02138 USA. RP Serreze, DV (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM dvs@jax.org OI Besra, Gurdyal/0000-0002-5605-0395 FU Medical Research Council [G0400421]; NCI NIH HHS [CA34196]; NIAID NIH HHS [AI45889, AI51392]; NIDDK NIH HHS [DK27722, DK36175, DK46266, DK51090]; Wellcome Trust NR 46 TC 19 Z9 19 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 2006 VL 177 IS 5 BP 2939 EP 2947 PG 9 WC Immunology SC Immunology GA 077BN UT WOS:000240002800025 PM 16920929 ER PT J AU Chen, JP Lu, HL Lai, SL Campanella, GS Sung, JM Lu, MY Wu-Hsieh, BA Lin, YL Lane, TE Luster, AD Liao, F AF Chen, Jia-Perng Lu, Hsin-Lin Lai, Szu-Liang Campanella, Gabriele S. Sung, Jui-Ming Lu, Mei-Yi Wu-Hsieh, Betty A. Lin, Yi-Ling Lane, Thomas E. Luster, Andrew D. Liao, Fang TI Dengue virus induces expression of CXC chemokine ligand 10/IFN-gamma-inducible protein 10, which competitively inhibits viral binding to cell surface heparan sulfate SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; ANTIBODY-DEPENDENT ENHANCEMENT; NATURAL-KILLER-CELLS; HEMORRHAGIC-FEVER; YELLOW-FEVER; IN-VIVO; INDUCIBLE PROTEIN-10; ENDOTHELIAL-CELLS; T-LYMPHOCYTES; HUMAN LIVER AB Dengue virus is an arthropod-borne flavivirus that causes a mild febrile illness, dengue fever, or a potentially fatal syndrome, dengue hemorrhagic fever/dengue shock syndrome. Chemokines primarily orchestrate leukocyte recruitment to the areas of viral infection, which makes them critical mediators of immune and inflammatory responses. In the present study, we investigated the induction and function of chemokines in mice early after infection with dengue virus in vivo. We found that CXCL10/IFN-gamma-inducible protein 10 (IP-10) expression was rapidly and transiently induced in liver following infection. The expressed CXCL10/IP-10 likely mediates the recruitment of activated NK cells, given that anti-CXCL10/IP-10-treated mice showed diminished NK cell infiltration and reduced hepatic expression of effector molecules in activated NK cells after dengue virus infection. Of particular interest, we found that CXCL10/IP-10 also was able to inhibit viral binding to target cells in vitro. Further investigation revealed that various CXCL10/IP-10 mutants, in which the residues that mediate the interaction between the chemokine and heparan sulfate were substituted, failed to exert the inhibitory effect on dengue binding, which suggests that CXCL10/IP-10 competes with dengue virus for binding to heparan sulfate on the cell surface. Moreover, subsequent plaque assays showed that this inhibition of dengue binding blocked viral uptake and replication. The inhibitory effect of CXCL10/IP-10 on the binding of dengue virus to cells may represent a novel contribution of this chemokine to the host defense against viral infection. C1 Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Natl Taiwan Univ, Coll Med, Grad Inst Immunol, Taipei 10764, Taiwan. Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan. Univ Calif Irvine, Dept Mol Biol, Irvine, CA 92679 USA. RP Liao, F (reprint author), Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. EM fl9z@ibms.sinica.edu.tw OI WU-HSIEH, BETTY AN-YE/0000-0003-1522-2055 NR 68 TC 47 Z9 48 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2006 VL 177 IS 5 BP 3185 EP 3192 PG 8 WC Immunology SC Immunology GA 077BN UT WOS:000240002800053 PM 16920957 ER PT J AU Kokkotou, E Torres, D Moss, AC O'Brien, M Grigoriadis, DE Karalis, K Pothoulakis, C AF Kokkotou, Efi Torres, Daniel Moss, Alan C. O'Brien, Michael Grigoriadis, Dimitri E. Karalis, Katia Pothoulakis, Charalabos TI Corticotropin-releasing hormone receptor 2-deficient mice have reduced intestinal inflammatory responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DIFFICILE TOXIN-A; UROCORTIN-II; ULCERATIVE-COLITIS; CROHNS-DISEASE; COLONIC-MUCOSA; G-PROTEIN; CRF; EXPRESSION; PEPTIDE; TYPE-2 AB Corticotropin-releasing hormone (CRH) and urocortins (Ucn) bind with various affinities to two G-protein-coupled receptors, CRHR1 and CRHR2, which are expressed in brain and in peripheral tissues, including immune cells. CRHR2-deficient Mice display anxiety-like behavior, hypersensitivity to stress, altered feeding behavior and metabolism, and cardiovascular abnormalities. However, the phenotype of these mice in inflammatory responses has not been determined. In the present study we found that compared with wild-type CRHR2-null mice developed substantially reduced intestinal inflammation and had lower intestinal mRNA expression of the potent chemoattractants keratinocyte chemokine and monocyte chemoattractant protein 1 following intraluminal exposure to Clostridium difficile toxin A, a potent enterotoxin that mediates antibiotic-associated diarrhea and colitus in humans. This effect was recapitulated by administration of astressin 2B, a selective CRHR2 antagonist, before toxin A exposure. Moreover, Ab array analysis revealed reduced expression of several inflammatory chemokines, including keratinocyte chemokine and monocyte chemoattractant protein 1 in toxin A-exposed mice pretreated with astressin 2B. Real-time RT-PCR of wild-type mouse intestine showed that only UcnII, but not other Ucn, was significantly up-regulated by ileal administration of toxin A at 4 h compared with buffer exposure. We also found that human colonic epithelial HT-29 cells express CRHR2 alpha mRNA, whereas expression of beta and gamma spliced variants was minimal. Moreover, treatment of HT-29 cells with UcnII, which binds exclusively to CRHR2. stimulated expression of IL-8 and monocyte chemoattractant protein 1. Taken together, these results provide direct evidence that CRHR2 mediates intestinal inflammatory responses via release of proinflammatory mediators at the colonocyte level. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Endocrinol, Boston, MA 02215 USA. Neurocrine Biosci Inc, Dept Mol Biol, San Diego, CA USA. Boston Univ, Med Ctr, Dept Pathol, Boston, MA USA. Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. RP Pothoulakis, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Dana 601,330 Brookline Ave, Boston, MA 02215 USA. EM cpothoul@bidmc.harvard.edu FU NIDDK NIH HHS [DK 47977, P30 DK040561-11, P0-1 DK 33506, P30 DK040561, DK 38458] NR 50 TC 58 Z9 59 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2006 VL 177 IS 5 BP 3355 EP 3361 PG 7 WC Immunology SC Immunology GA 077BN UT WOS:000240002800072 PM 16920976 ER PT J AU Ascon, DB Lopez-Briones, S Liu, MC Ascon, M Savransky, V Colvin, RB Soloski, MJ Rabb, H AF Ascon, Dolores B. Lopez-Briones, Sergio Liu, Manchang Ascon, Miguel Savransky, Vladimir Colvin, Robert B. Soloski, Mark J. Rabb, Hamid TI Phenotypic and functional characterization of kidney-infiltrating lymphocytes in renal ischemia reperfusion injury SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL DEFICIENCY; T-CELL; ISCHEMIA/REPERFUSION INJURY; UP-REGULATION; CD69; GAMMA; MICE; IDENTIFICATION; ASSOCIATION; EXPRESSION AB T and B lymphocytes have been implicated in the pathogenesis of renal ischemia reperfusion injury (IRI). The trafficking of lymphocytes into kidneys during IRI has been postulated to underlie this effect, but has not been rigorously studied. We therefore characterized the lymphocyte populations infiltrating into mouse kidneys 3 and 24 h after renal IRI. Immunohistochemistry and flow cytometry staining of kidney lymphocytes showed increased trafficking of CD3(+) T cells and CD19(+) B cells in both sham-operated and IRI mice 3 h after renal IRI. In the IRI mice, increased infiltration of NK1.1(+) and CD4(+)NK1.1(+) cells compared with normal and sham-operated mice was observed 3 and 24 h after renal IRI, respectively. After 24 h of renal IRI, the decreased percentages of CD3(+), CD19(+), and NK1.1(+) populations in the IRI mice compared with control groups were observed. Increased TNF-alpha and IFN-gamma production of kidney infiltration CD3(+) T cells in IRI mice but not sham-operated mice was found. Unexpectedly, isolation and transfer of kidney-infiltrating lymphocytes 24 h after renal IRI into T cell-deficient mice reduced their functional and histological injury after renal IRI, suggesting that kidney-infiltrating lymphocytes could have a protective function. These quantitative, qualitative, and functional changes in kidney lymphocytes provide mechanistic insight into how lymphocytes modulate IRI, as well as demonstrating that abdominal surgery alone leads to lymphocyte changes in kidney. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Rabb, H (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Ross Res Bldg,Room 970,720 Rutland Ave, Baltimore, MD 21205 USA. EM hrabb1@jhmi.edu OI Lopez-Briones, Sergio/0000-0003-0273-0958 FU NIDDK NIH HHS [R0-1 DK54770] NR 35 TC 89 Z9 95 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2006 VL 177 IS 5 BP 3380 EP 3387 PG 8 WC Immunology SC Immunology GA 077BN UT WOS:000240002800075 PM 16920979 ER PT J AU Siddique, MA Hartman, KE Dragileva, E Dondero, M Gebretsadik, T Shintani, A Peiperl, L Valentine, F Kalams, SA AF Siddique, M. Atif Hartman, Kelly E. Dragileva, Ella Dondero, Maria Gebretsadik, Tebeb Shintani, Ayumi Peiperl, Laurence Valentine, Fred Kalams, Spyros A. TI Low CD4(+) T cell nadir is an independent predictor of lower HIV specific immune responses in chronically HIV-1-infected subjects receiving highly active antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LYMPHOCYTE; IMMUNODEFICIENCY; INFECTION; EFFECTOR; VIREMIA AB The influence of CD4(+) T cell nadirs on human immunodeficiency virus (HIV)-specific immune responses in subjects with apparently normal CD4(+) T cell counts is not known. We evaluated the frequency of HIV-1-specific immune responses in a cohort of patients with complete viral suppression (HIV-1 RNA load, < 50 copies/mL) who were receiving highly active antiretroviral therapy and had a wide range of CD4(+) T cell nadirs. We found positive associations between CD4(+) T cell nadirs and the magnitude of HIV-specific CD8(+) T cell responses (P = .02) and of T cell helper responses (P = .04). These data show the CD4(+) T cell nadir to be an independent predictor of HIV-specific CD4(+) and CD8(+) T cell responses in HIV-1-infected subjects with optimal suppression of viremia. C1 Vanderbilt Univ, Med Ctr, Infect Dis Unit, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. AIDS Clin Trial Grp, Operat Ctr, Silver Spring, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NYU, Med Ctr, New York, NY 10016 USA. RP Kalams, SA (reprint author), Vanderbilt Univ, Med Ctr, Infect Dis Unit, Dept Med, 1161 21st Ave,MCN-A4103, Nashville, TN 37232 USA. EM spyros.a.kalams@vanderbilt.edu NR 15 TC 23 Z9 23 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2006 VL 194 IS 5 BP 661 EP 665 DI 10.1086/505913 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 078HH UT WOS:000240092800018 PM 16897665 ER PT J AU Chan, ESL Fernandez, P Merchant, AA Desai, A Montesinos, MC Tung, CF Khoa, DN Pillinger, MH Reiss, AB Tomic-Canic, M Chen, JF Schwarzschild, MA Cronstein, BN AF Chan, E. S. L. Fernandez, P. Merchant, A. A. Desai, A. Montesinos, M. C. Tung, C. F. Khoa, D. N. Pillinger, M. H. Reiss, A. B. Tomic-Canic, M. Chen, J. F. Schwarzschild, M. A. Cronstein, B. N. TI Adenosine A(2A) receptors and dermal fibrosis: a pathogenic role for adenosine in diffuse dermal fibrosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Meeting Abstract C1 [Chan, E. S. L.; Fernandez, P.; Merchant, A. A.; Desai, A.; Montesinos, M. C.; Tung, C. F.; Khoa, D. N.; Pillinger, M. H.; Tomic-Canic, M.; Cronstein, B. N.] NYU, Sch Med, New York, NY USA. [Reiss, A. B.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Chen, J. F.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Schwarzschild, M. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. OI Montesinos, M. Carmen/0000-0003-1801-311X NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD SEP PY 2006 VL 11 IS 1 BP 144 EP 144 PG 1 WC Dermatology SC Dermatology GA 265JV UT WOS:000253355800034 ER PT J AU Saad, AF Virella, G Chassereau, C Boackle, RJ Lopes-Virella, MF AF Saad, Antonio F. Virella, Gabriel Chassereau, Charlyne Boackle, Robert J. Lopes-Virella, Maria F. TI OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages SO JOURNAL OF LIPID RESEARCH LA English DT Article DE oxidized low density lipoprotein; autoimmunity; atherosclerosis; activated macrophages; inflammation; oxidized low density lipoprotein immune complexes; oxidized low density lipoprotein antibodies ID LOW-DENSITY-LIPOPROTEIN; HUMAN ATHEROSCLEROTIC LESIONS; CORONARY-ARTERY-DISEASE; OXIDIZED LDL; HUMAN MONOCYTES; IMMUNOHISTOCHEMICAL LOCALIZATION; PITTSBURGH EPIDEMIOLOGY; DIABETES COMPLICATIONS; END-PRODUCTS; ANTIBODIES AB Oxidized low density lipoprotein (OxLDL) is immunogenic and induces autoimmune responses in humans. OxLDL antibodies are predominantly of the proinflammatory IgG1 and IgG3 isotypes. We tested the capacity of immune complexes prepared with copper-oxidized human LDL and affinity chromatography-purified human OxLDL antibodies [OxLDL-immune complexes (ICs)] to activate complement and to induce cytokine release by MonoMac 6 (MM6) cells and by primary human macrophages. The levels of C4d and C3a were significantly higher in human serum incubated with OxLDL-ICs than after incubation with OxLDL or OxLDL antibody, indicating complement activation by the classical pathway. MM6 cells and primary human macrophages were incubated with OxLDL-ICs, with or without prior conditioning with interferon-g. After 18 h of incubation, both MM6 cells and primary human macrophages released significantly higher levels of proinflammatory cytokines after incubation with OxLDL-ICs than after incubation with OxLDL or with OxLDL antibody, both in primed and unprimed cells. OxLDL-ICs were more potent activators of MM6 cells than keyhole limpet hemocyanin-ICs. Blocking Fc gamma receptor I (Fc gamma RI) with monomeric IgG1 significantly depressed the response of MM6 cells to OxLDL-ICs. In conclusion, human OxLDL-ICs have proinflammatory properties, as reflected by their capacity to activate the classical pathway of complement and to induce proinflammatory cytokine release from MM6 cells and primary human macrophages. C1 Ralph H Johnson Med Ctr Dept Vet Affairs, Charleston, SC USA. Med Univ S Carolina, Dept Med, Div Endocrinol Metab Nutr, Charleston, SC USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC USA. Med Univ S Carolina, Coll Dent Med, Dept Stomatol, Charleston, SC USA. RP Lopes-Virella, MF (reprint author), Ralph H Johnson Med Ctr Dept Vet Affairs, Charleston, SC USA. EM virellam@musc.edu FU NHLBI NIH HHS [P01 HL-55782] NR 43 TC 64 Z9 66 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2006 VL 47 IS 9 BP 1975 EP 1983 DI 10.1194/jlr.M600064-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 081XV UT WOS:000240351800010 PM 16804192 ER PT J AU Pugh, MJV Hanlon, JT Zeber, JE Bierman, A Cornell, J Berlowitz, DR AF Pugh, Mary Jo V. Hanlon, Joseph T. Zeber, John E. Bierman, Arlene Cornell, John Berlowitz, Dan R. TI Assessing potentially inappropriate prescribing in the elderly veterans affairs population using the HEDIS 2006 quality measure SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Article DE geriatrics; quality of health care; benchmarking; pharmacoepidemiology ID CLINICAL-PRACTICE GUIDELINES; NURSING-HOME RESIDENTS; MEDICATION USE; DRUG-USE; EXPLICIT CRITERIA; CARE PATIENTS; OUTPATIENTS; DEPRESSION; MORTALITY; ENROLLEES AB BACKGROUND: Studies have found that 20% to 25% of older patients receive drugs identified as inappropriate by the 1997 Beers criteria. After the addition of 22 new drugs to the 2003 Beers criteria, the National Committee on Quality Assurance convened an expert consensus panel to identify which drugs from the 2003 Beers criteria should always be avoided in the elderly. The resulting list of drugs to avoid was added to the 2006 Health Plan Employer Data and Information Set (HEDIS) to measure the quality of prescribing for the elderly. OBJECTIVE: To use HEDIS 2006 criteria to determine the rate of potentially inappropriate prescribing in the elderly (PIPE) and to determine if patient risk factors are similar to those found using Beers criteria. METHODS: This cross-sectional database study identified older patients receiving drugs included in the HEDIS 2006 criteria using national data from the Veterans Health Administration. Patients aged 65 years or older on October 1, 1999, with at least 2 outpatient visit days during fiscal year 2000, ending September 30, or outpatient visits in fiscal years 1999 and 2000 were included (N = 1,096,361). Multivariable logistic regression analyses stratified by gender identified patient characteristics associated with increased risk of HEDIS 2006 drug exposure. Since oral estrogens were considered appropriate at the time of this study, they were excluded from the list of HEDIS 2006 drugs. RESULTS: Overall, 19.6% of older veterans were exposed to HEDIS 2006 drugs-23.3% of older veteran women and 19.2% of older veteran men. The most commonly prescribed HEDIS 2006 drugs were antihistamines (received by 9.0% of men and 10.7% of women), opioid analgesics (received by 4.6% of men and 5.8% of women), and skeletal muscle relaxants (received by 4.3% of men and 5.3% of women). Propoxyphene was the most commonly used HEDIS 2006 drug, received by 4.5% of men and 5.7% of women, followed by diphenhydramine, received by 3.5% of men and 4.7% of women, and hydroxyzine, received by 3.2% of both men and women. Patients receiving 10 or more medications of any type were at greatest risk of exposure. Men were 8.2 times more likely to receive at least 1 HEDIS 2006 drug than those taking 1 to 3 drugs of any type (95% confidence interval [CI], 8.0-8.4), while women were 9.6 times more likely (95% Cl, 8.2-11.2). CONCLUSIONS: Even though we included a slightly different list of drugs to avoid, results for the HEDIS 2006 measure were similar to those of the 1997 Beers criteria. The HEDIS 2006 drugs are commonly prescribed, and there is a distinct need for direct evidence linking HEDIS 2006 PIPE exposure to adverse patient outcomes. To reduce PIPE, it seems necessary to provide additional evidence for clinicians through the conducting of a well-designed study to assess patient outcomes associated with PIPE exposure as defined by the HEDIS criteria. C1 VERDICT, S Texas Vet Healthcare Syst, Audie L Murphy Div 11C6, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equit Res, Pittsburgh, PA USA. Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA 15260 USA. Univ Toronto, Sch Med, Toronto, ON, Canada. Univ Toronto, Sch Nursing, Toronto, ON, Canada. VA Hlth Serv Res & Dev Serv, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Pugh, MJV (reprint author), VERDICT, S Texas Vet Healthcare Syst, Audie L Murphy Div 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM PughM@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763 NR 60 TC 71 Z9 72 U1 0 U2 7 PU ACADEMY MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAG CARE PHARM JI J. Manag. Care Pharm. PD SEP PY 2006 VL 12 IS 7 BP 537 EP 545 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 096DA UT WOS:000241356000001 PM 16981799 ER PT J AU Wang, CH Gold, BG Kaler, LJ Yu, X Afentoulis, ME Burrows, GG Vandenbark, AA Bourdette, DN Offner, H AF Wang, Chunhe Gold, Bruce G. Kaler, Laurie J. Yu, Xiaolin Afentoulis, Michael E. Burrows, Gregory G. Vandenbark, Arthur A. Bourdette, Dennis N. Offner, Halina TI Antigen-specific therapy promotes repair of myelin and axonal damage in established EAE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE axonal loss; demyelination; multiple sclerosis; T lymphocytes ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; STEM-CELL TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; T-CELLS; INFLAMMATORY DEMYELINATION; BRAIN-TISSUE; LESIONS; MICE; DISEASES AB Inflammation results in CNS damage in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. It is uncertain how much repair of injured myelin and axons can occur following highly selective anti-inflammatory therapy in EAE and MS. In this study, SJL/J mice with established EAE were treated successfully with an antigen-specific recombinant T cell receptor ligand (RTL), RTL401, a mouse I-A(s)/PLP-139-151 construct, after the peak of EAE. To define the mechanisms by which late application of RTL401 inhibits EAE, we evaluated mice at different time points to assess the levels of neuroinflammation and myelin and axon damage in their spinal cords. Our results showed that RTL401 administered after the peak of acute EAE induced a marked reduction in inflammation in the CNS, associated with a significant reduction of demyelination, axonal loss and ongoing damage. Electron microscopy showed that RTL-treated mice had reduced pathology compared with mice treated with vehicle and mice at the peak of disease, as demonstrated by a decrease in continued degeneration, increase in remyelinating axons and the presence of an increased number of small, presumably regenerative axonal sprouts. These findings indicate that RTL therapy targeting encephalitogenic T cells may promote CNS neuroregenerative processes. C1 Portland VA Med Ctr, Neuroimmunol Res, Portland, OR USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. RP Wang, CH (reprint author), Portland VA Med Ctr, Neuroimmunol Res, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR USA. EM wangch@ohsu.edu FU NIAID NIH HHS [AI43960, R01 AI043960]; NINDS NIH HHS [NS46877, R42 NS046877, NS41965, R01 NS041965, NS47661, R01 NS047661, R41 NS046877] NR 35 TC 31 Z9 33 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2006 VL 98 IS 6 BP 1817 EP 1827 DI 10.1111/j.1471-4159.2006.04081 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 077MN UT WOS:000240033600011 PM 16899071 ER PT J AU Shinohara, ML Cantor, H AF Shinohara, M. L. Cantor, H. TI Innate immune mechanisms that promote development of effector and regulatory CD4 lineages in EAE (Experimental Autoimmune Encephalomyelitis) SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 34 EP 34 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100088 ER PT J AU Carr, DJJ Wuest, T Welner, R Pelayo, R Farber, J Luster, A Kincade, P AF Carr, D. J. J. Wuest, T. Welner, R. Pelayo, R. Farber, J. Luster, A. Kincade, P. TI CXCL10 but not CXCL9 deficient mice are highly sensitive to herpes simplex virus type 1 infection SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. NIH, NIAID, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 42 EP 42 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100106 ER PT J AU Noubade, R Zachary, JF Wagner, DD Blankenhorn, EP Owens, T Millward, J Teuscher, C AF Noubade, R. Zachary, J. F. Wagner, D. D. Blankenhorn, E. P. Owens, T. Millward, J. Teuscher, C. TI Endothelial cell Weibel-Palade bodies regulate blood brain barrier function and susceptibility to experimental allergic encephalomyelitis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Univ Vermont, Burlington, VT USA. Univ Illinois, Champaign, IL 61820 USA. CBR Inst Biomed Res, Boston, MA USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Montreal Neurol Inst, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 81 EP 81 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100184 ER PT J AU Vandenbark, AA Chou, YK Burrows, GG Link, JM AF Vandenbark, Arthur A. Chou, Yuan K. Burrows, Gregory G. Link, Jason M. TI B cells with preferential affinity for partial (alpha 1 beta 1) MHC class II molecules may regulate pathogenic T cells in experimental encephalomyelitis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 162 EP 162 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633101087 ER PT J AU Haslinger, R Ulbert, I Moore, CI Brown, EN Devor, A AF Haslinger, R. Ulbert, I. Moore, C. I. Brown, E. N. Devor, A. TI Analysis of LFP phase predicts sensory response of barrel cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LOCAL-FIELD POTENTIALS; SINGLE CORTICAL CELLS; NEURONS IN-VIVO; SOMATOSENSORY CORTEX; NEOCORTICAL NEURONS; EVOKED RESPONSES; ONGOING ACTIVITY; LESS-THAN-1 HZ; EEG PHENOMENA; LAYER 2/3 AB Several previous studies have shown the existence of Up and Down states and have linked their magnitude ( e. g., depolarization level) to the size of sensory-evoked responses. Here, we studied how the temporal dynamics of such states influence the sensory-evoked response to vibrissa deflection. Under alpha-chloralose anesthesia, barrel cortex exhibits strong quasi-periodic similar to 1-Hz local field potential ( LFP) oscillations generated by the synchronized fluctuation of large populations of neurons between depolarized ( Up) and hyperpolarized ( Down) states. Using a linear depth electrode array, we recorded the LFP and multiunit activity ( MUA) simultaneously across multiple layers of the barrel column and used the LFP to approximate the subthreshold Up-Down fluctuations. Our central finding is that the MUA response is a strong function of the LFP oscillation's phase. When only ongoing LFP magnitude was considered, the response was largest in the Down state, in agreement with previous studies. However, consideration of the LFP phase revealed that the MUA response varied smoothly as a function of LFP phase in a manner that was not monotonically dependent on LFP magnitude. The LFP phase is therefore a better predictor of the MUA response than the LFP magnitude is. Our results suggest that, in the presence of ongoing oscillations, there can be a continuum of response properties and that each phase may, at times, need to be considered a distinct cortical state. C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, MIT,Massachusetts Gen Hosp, Div Hlth Sci & Technol,Dept Anesthesia & Crit Car, Boston, MA 02115 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Haslinger, R (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Bldg 149 13th St MC 149-2301, Charlestown, MA 02129 USA. EM robhh@nmr.mgh.harvard.edu RI Moore, Christopher/C-5588-2009; Ulbert, Istvan/F-2213-2010 FU NIBIB NIH HHS [R01 EB-00790]; NIDA NIH HHS [R01 DA-015644]; NIMH NIH HHS [R01 MH-59733]; NINDS NIH HHS [NS-051188] NR 37 TC 23 Z9 23 U1 0 U2 4 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 2006 VL 96 IS 3 BP 1658 EP 1663 DI 10.1152/jn.01288.2005 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 072FJ UT WOS:000239659000063 PM 16775200 ER PT J AU Hashimoto, H Monserratt, L Nguyen, P Feil, D Harwood, D Mandelkern, MA Sultzer, DL AF Hashimoto, Hiroshi Monserratt, Lorena Nguyen, Peter Feil, Denise Harwood, Dylan Mandelkern, Mark A. Sultzer, David L. TI Anxiety and regional cortical glucose metabolism in patients with Alzheimer's disease SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Neuropsychiatry-Association CY FEB-MAR -, 2005 CL Bal Harbour, FL SP Amer Neuropsychiat Assoc ID POSTTRAUMATIC-STRESS-DISORDER; PANIC DISORDER; PSYCHOLOGICAL SYMPTOMS; NEUROPSYCHIATRIC INVENTORY; HUMAN AMYGDALA; SOCIAL PHOBIA; SPECT; ACTIVATION; AGITATION; PERFUSION AB In this study, the authors investigated the relationship between anxiety and regional cortical metabolism in Alzheimer's disease. Using the Neuropsychiatric Inventory (NPI), the authors evaluated anxiety in 41 patients with Alzheimer's disease. Regional cortical glucose metabolism was measured using [F-18] fluorodeoxyglucose positron emission tomography in the resting state. Relationships were assessed using voxel-based (SPM2) and anatomic region-based analyses. Higher NPI anxiety score (frequency X severity) was associated with lower metabolism in bilateral entorhinal cortex, anterior parahippocampal gyrus, and left superior temporal gyrus and insula. Functional activity changes in distinct regions of the cortex contribute to the expression of anxiety in Alzheimer's disease. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Hashimoto, H (reprint author), Osaka City Univ, Sch Med, Dept Neuropsychiat, Abeno Ku, 1-4-3 Asahi Machi, Osaka, Osaka 5458585, Japan. EM hashimotoh@med.osaka-cu.ac.jp FU NIMH NIH HHS [MH56031] NR 41 TC 15 Z9 16 U1 0 U2 0 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 2006 VL 18 IS 4 BP 521 EP 528 DI 10.1176/appi.neuropsych.18.4.521 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 103BX UT WOS:000241861800008 PM 17135378 ER PT J AU Barker, FG Butler, WE Smith, ER AF Barker, Fred G., II Butler, William E. Smith, Edward R. TI Summer shunt surgery - Reply SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2006 VL 105 IS 3 SU S BP 164 EP 164 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 077BC UT WOS:000240001700003 ER PT J AU Smith, ER Butler, WE Barker, FG AF Smith, Edward R. Butler, William E. Barker, Fred G., II TI Is there a "July phenomenon" in pediatric neurosurgery at teaching hospitals? SO JOURNAL OF NEUROSURGERY LA English DT Article DE craniotomy; shunt; mortality rate; pediatric neurosurgery ID LENGTH-OF-STAY; INTRACRANIAL ANEURYSM SURGERY; CEREBROSPINAL-FLUID SHUNT; SERIOUS MEDICAL ERRORS; INTENSIVE-CARE-UNIT; WORK HOURS; INTERHOSPITAL TRANSFERS; AMERICAN NEUROSURGERY; SURGICAL EXPERIENCE; BRAIN-TUMORS AB Object. Concern for patient safety, among other reasons, recently prompted sweeping changes in resident work policies in the US. Some have speculated that the arrival of new interns and residents at teaching hospitals each July might cause an annual transient increase in poor patient outcomes and inefficient care. Methods. Data were analyzed for 4323 craniotomies for tumor resection and 22,072 shunt operations performed in pediatric patients between 1988 and 2000 in US nonfederal hospitals (Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, Rockville, MD). In-hospital mortality rates, discharge outcome, complications, and efficiency measures (length of stay [LOS] and hospital charges) for patients treated in July and August were compared with similar data for patients in other months. There were no significant increases in any adverse end point for either tumor or shunt operations in July and August. Odds ratios (95% confidence interval [Cl]) for outcome of tumor craniotomies performed in July and August compared with outcome for tumor craniotomies performed in other months were as follows: for mortality rate, 0.43 (0.14-1.32); for adverse discharge disposition, 1.03 (0.71-1.51); for neurological complications, 1.00 (0.63-1.59); for transfusion, 0.70 (0.41-1.19). Hospital charges were 0.5% lower (range -6 to 5%) in July and August, and LOS was 3% shorter (range -8 to 3%). Odds ratios (95% CI) for July or August shunt surgery compared with shunt surgery performed in other months were as follows: for mortality rate, 0.96 (0.58-1.60); for adverse discharge disposition, 0.85 (0.66-1.11); for neurological complications, 1.27 (0.75-2.16); for transfusion, 0.81 (0.48-1.37). Hospital charges were 0.2% higher in July and August (range -3 to 3%), and LOS was 3% shorter (range -5 to 0.5%). Conclusions. Although moderate increases in some adverse end points could not be excluded, there was no evidence that brain tumor or shunt surgery performed in pediatric patients at US teaching hospitals during July and August is associated with more frequent adverse patient outcome or inefficient care than similar surgery performed during other months. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Childrens Hosp, Dept Neurol Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Yawkey 9E,Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 59 TC 35 Z9 35 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2006 VL 105 IS 3 SU S BP 169 EP 176 DI 10.3171/ped.2006.105.3.169 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 077BC UT WOS:000240001700005 PM 16970228 ER PT J AU Barker, FG AF Barker, Fred G., II TI Brain metastasis SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID RANDOMIZED-TRIAL; SINGLE METASTASES; RADIOTHERAPY; RADIOSURGERY; RADIATION; FEASIBILITY; SURGERY C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2006 VL 105 IS 3 BP 371 EP 372 DI 10.3171/jns.2006.105.3.371 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 076CI UT WOS:000239934200004 PM 16961128 ER PT J AU Hynynen, K McDannold, N Vykhodtseva, N Raymond, S Weissleder, R Jolesz, FA Sheikov, N AF Hynynen, Kullervo McDannold, Nathan Vykhodtseva, Natalia Raymond, Scott Weissleder, Ralph Jolesz, Ferenc A. Sheikov, Nickolai TI Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery SO JOURNAL OF NEUROSURGERY LA English DT Article DE blood-brain barrier; drug delivery system; ultrasonics; ultrasound contrast agent; magnetic resonance imaging ID FOCUSED ULTRASOUND; IN-VIVO; MAMMALIAN-TISSUES; RABBIT BRAIN; THERAPY; SKULL; PERMEABILITY; COMPILATION; PRESSURE; SURGERY AB Object. The goal of this study was to explore the feasibility of using low-frequency magnetic resonance (MR) image-guided focused ultrasound as a noninvasive method for the temporary disruption of the blood-brain barrier (BBB) at targeted locations. Methods. Rabbits were placed inside a clinical 1.5-tesla MR imaging unit, and sites in their brains were targeted for 20-second burst sonications (frequency 260 kHz). The peak pressure amplitude during the burst varied between 0.1 and 0.9 MPa. Each sonication was performed after an intravenous injection of an ultrasound contrast agent (Optison). The disruption of the BBB was evaluated with the aid of an injection of an MR imaging contrast agent (MAG-NEVIST). Additional tests involving the use of MION-47, a 20-nm magnetic nanoparticle contrast agent, were also performed. The animals were killed at different time points between 3 minutes and 5 weeks postsonication, after which light or electron microscopic evaluation was performed. The threshold for BBB disruption was approximately 0.2 MPa. More than 80% of the brain sites sonicated showed BBB disruption when the pressure amplitude was 0.3 MPa; at 0.4 MPa, this percentage was greater than 90%. Tissue necrosis, ischemia, and apoptosis were not found in tissue in which the pressure amplitude was less than 0.4 MPa; however, in a few areas of brain tissue erythrocytes were identified outside blood vessels following exposures of 0.4 MPa or higher. Survival experiments did not show any long-term adverse events. Conclusions. These results demonstrate that low-frequency ultrasound bursts can induce local, reversible disruption of the BBB without undesired long-term effects. This technique offers a potential noninvasive method for targeted drug delivery in the brain aided by a relatively simple low-frequency device. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Hynynen, K (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Biophys, 2075 Bayview Ave,Room S6 65B, Toronto, ON M4N 3M5, Canada. EM khynynen@sri.utoronto.ca FU NIBIB NIH HHS [EB003268, EB00705] NR 29 TC 162 Z9 168 U1 2 U2 28 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2006 VL 105 IS 3 BP 445 EP 454 DI 10.3171/jns.2006.105.3.445 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 076CI UT WOS:000239934200019 PM 16961141 ER PT J AU Shaw, LJ Heller, GV Casperson, P Miranda-Peats, R Slornka, P Friedman, J Hayes, SW Schwartz, R Weintraub, WS Maron, DJ Dada, M King, S Teo, K Hartigan, P Boden, WE O'Rourke, RA Berman, DS AF Shaw, Leslee J. Heller, Gary V. Casperson, Paul Miranda-Peats, Romalisa Slornka, Piotr Friedman, John Hayes, Sean W. Schwartz, Ronald Weintraub, William S. Maron, David J. Dada, Marcin King, Spencer Teo, Koon Hartigan, Pamela Boden, William E. O'Rourke, Robert A. Berman, Daniel S. CA COURAGE Investigators TI Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424 SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE randomized trial; gated myocardial perfusion SPECT; prognosis; secondary prevention ID CORONARY-ARTERY-DISEASE; AMERICAN-HEART-ASSOCIATION; PRACTICE GUIDELINES COMMITTEE; LONG-TERM; MEDICAL THERAPY; TASK-FORCE; HYPERCHOLESTEROLEMIC PATIENTS; PREVENTIVE CARDIOLOGY; PROGNOSTIC VALUE; SILENT ISCHEMIA AB Background: Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results: The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n = 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients' ischemic burdens. Conclusions: The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. Hartford Hosp, Hartford, CT 06115 USA. S Texas Vet Healthcare Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Rochester, Med Ctr, Rochester, NY 14627 USA. Vanderbilt Univ, Med Ctr, Christiana Med Ctr, Nashville, TN USA. McMaster Univ, Hamilton, ON L8S 4L8, Canada. RP Berman, DS (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Room 1258,Taper Bldg,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM daniel.berman@cshs.org NR 61 TC 26 Z9 28 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 2006 VL 13 IS 5 BP 685 EP 698 DI 10.1016/j.nuclcard.2006.06.134 PG 14 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 081ME UT WOS:000240320900014 PM 16945749 ER PT J AU Higgins, JP AF Higgins, John P. TI Increased right ventricular uptake on stress SPECT myocardial perfusion images in a patient with severe coronary artery disease SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article C1 Harvard Univ, Sch Med, Nucl Cardiol Sect, VA Boston Healthcare Syst,Cardiac Stress Lab, Boston, MA 02132 USA. RP Higgins, JP (reprint author), Harvard Univ, Sch Med, Nucl Cardiol Sect, VA Boston Healthcare Syst,Cardiac Stress Lab, Nucl Med 2C-120,1400 VFW Pkwy, Boston, MA 02132 USA. EM John.Higgins@va.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 2006 VL 13 IS 5 BP 725 EP 727 DI 10.1016/j.nuclcard.2006.06.115 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 081ME UT WOS:000240320900019 PM 16945754 ER PT J AU Fang, SC Eisen, EA Dai, HL Zhang, HX Hang, JQ Wang, XR Christiani, DC AF Fang, Shona C. Eisen, Ellen A. Dai, Helian Zhang, Hongxi Hang, Jingqing Wang, Xiaorong Christiani, David C. TI Cancer mortality among textile workers in Shanghai, China: A preliminary study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID COTTON DUST; INDUSTRY; RISK AB Objective: We assessed the association between cotton textile work and cancer mortality. Methods: The cancer mortality experience of 912 (444 cotton, 468 silk) textile workers in Shanghai, China, was compared. Workers were followed from 1981 to 2003. The associations between cotton textile work and death due to all cancers combined (with and without lung cancer) and to gastrointestinal cancers were estimated with Cox models, adjusting for age, work years, and pack-years. Results. There were 69 deaths. The adjusted hazard rate ratio (HR) was 2.10 (95% cmfidence interval [CI], 0.98 - 4.47) for all cancers combined and 2.56 (95% CI, 1.14-5.74) after excluding lung cancer. For gastrointestinal cancers, the adjusted HR was 2.09 (95 % CI, 0.83-5.27). Conclusions: These preliminary data suggest that, with the exception of lung cancer, cotton workers have significantly higher cancer mortality rates than silk workers. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Putuo Dist Peoples Hosp, Shanghai, Peoples R China. Harvard Univ, Sch Med, Pulm & Crit Care Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1407, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Lin, Sihao/A-8412-2012 FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OH02421] NR 17 TC 2 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD SEP PY 2006 VL 48 IS 9 BP 955 EP 958 DI 10.1097/01.jom.0000232527.76794.62 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 084IV UT WOS:000240527500012 PM 16966963 ER PT J AU Chima, KK Seldin, EB Dodson, TB AF Chima, Karindeep K. Seldin, Edward B. Dodson, Thomas B. TI Comparison of wound management methods after removal of maxillofacial osseous lesions SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Purpose: To evaluate outcomes associated with choice of wound management, ie, primary closure or healing by secondary intention, of osseous defects after excision of maxillofacial bone lesions as a guide to clinical practice. Patients and Methods: Using a retrospective cohort study design, we enrolled a sample composed of subjects treated for jaw lesions between 1995 and 2003. The primary predictor variable was the wound management choice of the residual jaw defect, classified as primary closure or healing by secondary intention. The primary outcome variable was postoperative inflammatory complications. Other study variables were grouped as demographic, medical/dental history, lesion information, preoperative complications, operative treatment, and follow-up information. Appropriate uni-, bi-, and multivariate statistics were computed. Results: The sample was composed of 93 subjects with 126 jaw lesions, of which 90 (71.4%) were managed by primary closure. In the bivariate analyses, tobacco use was statistically associated (P < .05) with wound management and near statistically associated (P = .06) with complications. In the multivariate model, after adjusting for the presence of multiple cysts and tobacco use, there was not a statistically significant difference between the 2 wound management choices in terms of postoperative complications. Conclusions: our results suggest that the choice of managing the osseous wound, ie, primary closure versus secondary intention, was not associated with increased risk of postoperative inflammatory complications. The implications of these findings are discussed below. (c) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org NR 5 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2006 VL 64 IS 9 BP 1398 EP 1403 DI 10.1016/j.joms.2006.05.025 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 078OW UT WOS:000240114100012 PM 16916675 ER PT J AU Chen, TC Bhatia, LS Halpern, EE Walton, DS AF Chen, Teresa C. Bhatia, Lini S. Halpern, Elkan E. Walton, David S. TI Risk factors for the development of aphakic glaucoma after congenital cataract surgery SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Ophthalmological-Society CY MAY 20-24, 2006 CL Half Moon Bay, CA SP Amer Ophthalmol Soc ID INTRAOCULAR-PRESSURE ELEVATIONS; PEDIATRIC LENSECTOMY; INFANTILE CATARACTS; COMPLICATIONS; CHILDREN; EYES AB Background: It is well-known that lensectomy surgery during the first year of life increases one's risk of aphakic glaucoma. However, it is controversial whether there is a specific time period during-the first year of life after which performing lensectomy surgery has a lower risk of aphakic glaucoma development. Patients and Methods: A retrospective chart review was performed of all patients seen by a pediatric glaucoma specialist from 1970 to 2003. Patients were included in the study if they underwent congenital cataract surgery. Cataracts were defined as congenital if they were identified within the first 6 months of life, were dominantly inherited, or were of the lamellar type. Aphakic glaucoma was defined as having repeated intraocular pressures > 25 mm Hg after congenital cataract surgery. Patients were excluded if they had any conditions that were independently associated with glaucoma. Results: A total of 368 eyes of 258 patients were included in the study. Of these, 216 (58.7%) eyes of 150 patients developed aphakic glaucoma. Risk factors of greatest significance (P < .0001) included having lensectomy within the first year of life and the development of postoperative complications. Conclusions: No specific age for lensectomy during the first year of life was associated with a decreased risk for development of aphakic glaucoma. Surgery for congenital cataracts should not be delayed if the only reason for delay is to prevent the development of aphakic glaucoma. C1 Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. E Tennessee State Univ, Dept Internal Med, Johnson City, TN USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. NR 35 TC 15 Z9 16 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD SEP-OCT PY 2006 VL 43 IS 5 BP 274 EP 280 PG 7 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 088BT UT WOS:000240787200006 PM 17022160 ER PT J AU Buecker, PJ Berenstein, M Gebhardt, MC Hornicek, FJ Mankin, HJ AF Buecker, Peter J. Berenstein, Mariela Gebhardt, Mark C. Hornicek, Francis J. Mankin, Henry J. TI Locking versus standard plates for allograft fixation after tumor resection in children and adolescents SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE allograft; bone tumors; fixation; locking plates ID RETRIEVED HUMAN ALLOGRAFTS; OSTEOARTICULAR ALLOGRAFTS; BONE ALLOGRAFTS; LIMB SALVAGE; RECONSTRUCTION; OSTEOSARCOMA; NONUNION; TIBIA; LCP AB Purpose: This investigation was undertaken to assess the performance of locking plates in comparison to standard compression plates for allograft fixation after resection of malignant primary skeletal tumors. Methods: Using a computerized database, patients younger than 18 years who had undergone resection of malignant skeletal tumors with allograft reconstruction from January 1998 through June 2004 were identified. Demographic, oncological, surgical, and follow-up data were collected, and comparison of outcomes with regard to allograft-host junction healing between locking and standard compression plates was undertaken. Results: Thirty-nine patients meeting the inclusion criteria were identified. Homogeneity of the study group with regards to age, sex, diagnosis, adjuvant therapy, and presence of metastases allowed for evaluation of allograft-host union as a relatively independent variable. Nine patients in the locking plate group (75%) united after the index procedure at an average of 13.1 months. Fifteen patients (55.6%) with compression plates healed after the initial reconstruction at an average of 14.6 months. Complications and secondary procedures were noted. Conclusions: Results of this investigation suggest that use of locking plates for allograft-host junction fixation is associated with improved union rates and less need for additional operations when compared with standard compression plates. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Naval Pedro Mallo, Buenos Aires, DF, Argentina. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp Boston, Boston, MA USA. RP Buecker, PJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 3B, Boston, MA 02114 USA. EM pjbuecker@hotmail.com NR 24 TC 10 Z9 12 U1 0 U2 2 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-OCT PY 2006 VL 26 IS 5 BP 680 EP 685 PG 6 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 080MU UT WOS:000240252800021 PM 16932111 ER PT J AU Spinale, FG Escobar, GP Hendrick, JW Clark, LL Camens, SS Mingoia, JP Squires, CG Stroud, RE Ikonomidis, JS AF Spinale, Francis G. Escobar, G. Patricia Hendrick, Jennifer W. Clark, Leslie L. Camens, Sarah S. Mingoia, Joseph P. Squires, Christina G. Stroud, Robert E. Ikonomidis, John S. TI Chronic matrix metalloproteinase inhibition following myocardial infarction in mice: Differential effects on short and long-term survival SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LEFT-VENTRICULAR ENLARGEMENT; PREVENTS CARDIAC RUPTURE; HEART-FAILURE; TARGETED DELETION; MATRIX-METALLOPROTEINASE-9; MOLECULES; STRESS; TRIALS; CANCER AB Left ventricular (LV) remodeling occurs after myocardial infarction (MI), and the matrix metalloproteinases ( MMPs) contribute to adverse LV remodeling after MI. Short-term pharmacological MMP inhibition (MMPi; days to weeks) in animal models of MI have demonstrated a reduction in adverse LV remodeling. However, the long-term effects (months) of MMPi on survival and LV remodeling after MI have not been examined. MI was induced in adult mice (n = 131) and, at 3 days post-MI, assigned to MMPi [MI- MMPi: (s)-2-(4-bromo-biphenyl-4-sulfonylamino)3- methyl-butyric acid (PD200126), 7.5 mg/day/ p.o., n = 64] or untreated (MI-only, n = 67). Unoperated mice ( n = 16) served as controls. The median survival in the MI- only group was 5 days, whereas median survival was significantly greater in the MI-MMPi group at 38 days ( p < 0.05). However, with prolonged MMPi ( > 120 days), a significant divergence in the survival curves occurred in which significantly greater mortality was observed with prolonged MMPi ( p < 0.05). LV echo-cardiography at 6 months revealed LV dilation in the MI- only and MI- MMPi groups ( 154 +/- 14 and 219 +/- 24 mu l) compared with control (67 +/- 14 mu l, p < 0.05), with a greater degree of dilation in the MI- MMPi group ( p < 0.05). MMPi conferred a beneficial effect on survival early post-MI, but prolonged MMPi ( > 3 months) was associated with higher mortality and adverse LV remodeling. These unique results suggest that an optimal temporal window exists with respect to pharmacological interruption of MMP activity in the post-MI period. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NCRR NIH HHS [P20 RR16434]; NHLBI NIH HHS [P01 HL48788-08, HL59165] NR 37 TC 22 Z9 26 U1 1 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 2006 VL 318 IS 3 BP 966 EP 973 DI 10.1124/jpet.106.104455 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075IT UT WOS:000239878900005 PM 16757539 ER PT J AU Mukhin, YV Gooz, M Raymond, JR Garnovskaya, MN AF Mukhin, Yurii V. Gooz, Monika Raymond, John R. Garnovskaya, Maria N. TI Collagenase-2 and-3 mediate epidermal growth factor receptor transactivation by bradykinin B-2 receptor in kidney cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACTIVATED PROTEIN-KINASE; GONADOTROPIN-RELEASING-HORMONE; COLONIC EPITHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; MATRIX METALLOPROTEINASES; ANGIOTENSIN-II; RENAL FIBROSIS; MAP KINASE; TRANSFORMING GROWTH; COUPLED RECEPTORS AB We have previously shown that stimulation of extracellular signal-regulated protein kinase (ERK) by bradykinin (BK) in murine inner medullary collecting duct (mIMCD)-3 cells is mediated by epidermal growth factor receptor ( EGFR) transactivation. The mechanism of EGFR transactivation seemed to be novel, because it does not require phospholipase C, Ca2+, calmodulin, protein kinase C, G alpha(i) subunits, or EGFR-B-2 receptor heterodimerization. In this study, we demonstrated the involvement of matrix metalloproteinases ( MMPs) in B-2 receptor-induced EGFR transactivation using their broad-spectrum inhibitors batimastat and N-[(2R)-2-( hydroxamidocarbonylmethyl)4- methylpentanoyl]-L-tryptophan methylamide ( Galardin) (GM-6001). Selective inhibitors for collagenase-2 and -3 (MMP-8 and MMP-13, respectively) blocked BK-induced EGFR phosphorylation and ERK activation, whereas inhibitors for MMP-1, -2, -3, - 7, or - 9 were without effect. Transfection of mIMCD- 3 cells with MMP-8 small interfering RNA ( siRNA) resulted in similar to 50% decrease of BK-induced ERK activation. A neutralizing antibody against MMP-13 as well as transfection with MMP-13 siRNA produced a similar effect. Inhibition of both collagenases resulted in similar to 65% decrease of BK-induced ERK activation, supporting roles for both enzymes. Stimulation of mIMCD-3 cells with 10 nM BK increased the activity of collagenases in concentrated culture media within 10 min. Moreover, recombinant MMP-13 and MMP-8, when applied to mIMCD-3 cells for 10 min without BK, stimulated tyrosine phosphorylation of EGFR and caused similar to 250% increase over basal ERK phosphorylation comparable with BK-induced ERK activation. Collagenases-induced ERK activation was inhibited by 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG-1478) and thus dependent on EGFR tyrosine kinase activity. This study demonstrates a novel role for collagenase-2 and -3 in signaling of the G(q)-coupled BK B-2 receptor in mIMCD-3 cells. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, 96 Jonathan Lucas St,Room 829 CSB,POB 250623, Charleston, SC 29425 USA. EM garnovsk@musc.edu FU NCRR NIH HHS [S10RR013005]; NIDDK NIH HHS [DK52448-02, DK02694] NR 40 TC 14 Z9 16 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2006 VL 318 IS 3 BP 1033 EP 1043 DI 10.1124/jpet.106.104000 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075IT UT WOS:000239878900012 PM 16717107 ER PT J AU Lopez-Meraz, ML Neri-Bazan, L Rocha, L AF Lopez-Meraz, M. L. Neri-Bazan, L. Rocha, L. TI Indorenate modifies a(1)-adrenergic and benzodiazepine receptor binding in the rat brain: an autoradiography study SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID DORSAL RAPHE NUCLEUS; ANXIOLYTIC ACTION; 5-HT1A RECEPTOR; SEROTONIN; SUBTYPES; AGONISTS; GABA; RECOMBINANT; INVOLVEMENT; ANTAGONISTS AB Indorenate (5-methoxytryptamine-ss-methylcarboxylate) is a 5-HT1A receptor agonist that produces anti hypertensive, anxiolytic, antidepressant and anticonvulsant effects. However, there is evidence suggesting that these effects could involve the activation of benzodiazepine (BZD) receptors but not the activation of a(1)-adrenergic receptors. The goal of this study was to analyse the effect of inclorenate on a(1)-adrenergic and BZD receptor binding in specific rat brain areas by using in-vitro autoradiography. Coronal brain sections from male Wistar rats were used for labelling 5-HT1A (H-3-8-OH-DFAT, 2 nM), a(1)-adrenergic (H-3-prazosin, 2 nM) and BZD (H-3-flunitrazepam, 2 nM) receptor binding in the presence or absence of inclorenate (1 mu m). Indorenate totally displaced H-3-8-OH-DPAT binding in all the brain areas evaluated. It decreased H-3-prazosin binding just in the frontal (30%) and sensorimotor (32%) cortices and in the thalamus (21%). Additionally, inclorenate diminished H-3-flunitrazepam binding only in the cingulate (16%) and piriform (18%) cortices as well as in the dorsal raphe nucleus (18%). These results confirm that inclorenate is a 5-HT1A ligand and suggest the possible participation of a(1)-adrenergic and BZD receptors in its pharmacological properties. C1 Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, Los Angeles, CA USA. Ctr Invest & Estudios Avanzados, Dept Farmacobiol, Mexico City, DF, Mexico. RP Lopez-Meraz, ML (reprint author), VA Med Ctr, 11301 Wilshire Blvd,Bldg 114,Room 139,W, Los Angeles, CA 90073 USA. EM lopezmerazml@ucla.edu NR 38 TC 2 Z9 2 U1 0 U2 0 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD SEP PY 2006 VL 58 IS 9 BP 1243 EP 1248 DI 10.1211/jpp.58.9.0011 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 085DG UT WOS:000240582800011 PM 16945183 ER PT J AU Ma, QF AF Ma, Qiufu TI Transcriptional regulation of neuronal phenotype in mammals SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID DORSAL SPINAL-CORD; EMBRYONIC STEM-CELLS; GRANULE CELLS; SEROTONERGIC NEURONS; MOLECULAR-MECHANISMS; PRONEURAL GENES; MOTOR-NEURONS; COMBINATORIAL EXPRESSION; LINEAGE DETERMINATION; DOPAMINERGIC-NEURONS AB Transcription factors (TFs) play pivotal roles in directing the formation of neurons and glia. Here I will review the recent genome-scale analysis of the expression of TFs in the developing mouse nervous system and discuss the logic by which TFs control the establishment of neuronal phenotype. Accumulating evidence suggests that while combinatorial action of TFs is able to define the basic framework of the nervous system, other control mechanisms, such as stochastic and epigenetic regulation of gene expression, also contribute to the generation of nerve cell diversity. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM qiufu_ma@dfci.harvard.edu NR 121 TC 38 Z9 38 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2006 VL 575 IS 2 BP 379 EP 387 DI 10.1113/jphysiol.2006.113449 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 077DD UT WOS:000240007000011 PM 16825304 ER PT J AU Stewart, SE Yen, CH Stack, DE Jenike, MA AF Stewart, S. Evelyn Yen, Chen-Hsing Stack, Denise Egan Jenike, Michael A. TI Outcome predictors for severe obsessive-compulsive patients in intensive residential treatment SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE obsessive-compulsive disorder; outcome; treatment; predictor; gender; severity ID COGNITIVE-BEHAVIOR THERAPY; SEROTONIN REUPTAKE INHIBITORS; TREATMENT RESPONSE; FOLLOW-UP; INTRAVENOUS CLOMIPRAMINE; PERSONALITY-DISORDER; CLINICAL PREDICTORS; DRUG RESPONSE; OPEN TRIAL; PHARMACOTHERAPY AB Intensive residential treatment (IRT) is an effective management approach for those with severe obsessive-compulsive disorder (OCD). This study aimed to identify IRT response predictors for clinical and research use. Consecutive subjects admitted to the Massachusetts General Hospital/McLean OCD Institute (OCDI) between February 1997 and June 2003 were included (N = 476). IRT responder and non-responder group characteristics were compared using t-tests and 2 analyses. Multiple regression analysis modeled relationships between final OCD severity (Yale-Brown Obsessive-Compulsive scale scores) and predictor variables, while accounting for multicollinearity and potential outliers. Treatment responders comprised 59.3% of the treatment sample. Responders had significantly fewer males (p = 0.02), lower depression severity (p = 0.03), poorer psychosocial functioning (P = 0.03) and fewer tic disorders (0.04), but were not different with respect to admission length, age, marital or employment status, OCD onset, family OCD history, treatment or admission history. In the final regression model, decreased initial OCD severity (p < 0.001), female gender (p = 0.003) and better initial psychosocial functioning (Work and Social Adjustment scale scores) (p = 0.003) were predictors of less severe OCD at discharge (adjusted R-square = 0.28). Depression severity (Beek Depression Inventory scores) and insight were not predictive of treatment outcome. Future research is necessary to elucidate putative relationships between gender and OCD psychopathology, and to understand the interplay of psychosocial factors, OCD severity and treatment outcome. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Obsess Compuls Disorder Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. McLean Hosp, Obsess Compuls Disorder Inst, Belmont, MA 02178 USA. RP Stewart, SE (reprint author), Massachusetts Gen Hosp, Obsess Compuls Disorder Clin, 185 Cambridge St,2nd Floor Simches, Boston, MA 02114 USA. EM estewart1@partners.org RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 NR 74 TC 31 Z9 31 U1 4 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD SEP PY 2006 VL 40 IS 6 BP 511 EP 519 DI 10.1016/j.jpsychires.2005.08.007 PG 9 WC Psychiatry SC Psychiatry GA 080LT UT WOS:000240250000006 PM 16229857 ER PT J AU Hajcak, G Franklin, ME Simons, RF Keuthen, NJ AF Hajcak, Greg Franklin, Martin E. Simons, Robert F. Keuthen, Nancy J. TI Hairpulling and skin picking in relation to affective distress and obsessive-compulsive symptoms SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE trichotillomania; skin picking; prevalence; obsessive-compulsive spectrum disorder ID STATE WORRY QUESTIONNAIRE; ANXIETY-STRESS SCALES; PSYCHOMETRIC PROPERTIES; CLINICAL CHARACTERISTICS; SPECTRUM DISORDERS; COLLEGE-STUDENTS; HAIR PULLERS; TRICHOTILLOMANIA; PREVALENCE; DEPRESSION AB The current study examined the frequency and associated distress of both hairpulling and skin picking behaviors in 1,324 college students using the Massachusetts General Hospital Hairpulling Scale (MGHHS) and Skin Picking Scale (SPS). In this sample, many participants reported significant distress secondary to both hairpulling and skin picking. Participants who endorsed relatively frequent hairpulling or skin picking (N = 72) were scheduled for a follow-up testing session to further assess the relationship between these behaviors and measures of affective distress. Compared to a control sample, the follow-up sample endorsed significantly more symptoms of anxiety and stress reactivity, and had higher scores on a measure of obsessive-compulsive symptoms. C1 Univ Delaware, Dept Psychol, Newark, DE 19716 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Penn, Dept Psychiat, Ctr Treatment & Study Anxiety, Philadelphia, PA 19104 USA. RP Hajcak, G (reprint author), Univ Delaware, Dept Psychol, Newark, DE 19716 USA. EM hajcak@psych.udel.edu RI Citations, TLC SAB/C-4006-2011 NR 54 TC 16 Z9 16 U1 7 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 2006 VL 28 IS 3 BP 179 EP 187 DI 10.1007/s10862-005-9001-x PG 9 WC Psychology, Clinical SC Psychology GA 077UA UT WOS:000240054800006 ER PT J AU Eapen, V Pauls, DL Robertson, MM AF Eapen, Valsamma Pauls, David L. Robertson, Mary May TI The role of clinical phenotypes in understanding the genetics of obsessive-compulsive disorder SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE obsessive-compulsive disorder; clinical phenotypes; genetics; segregation analysis ID LA-TOURETTE-SYNDROME; COMPLEX SEGREGATION ANALYSIS; FAMILY-HISTORY; EARLY-ONSET; GILLES; SYMPTOMS; ADOLESCENTS; CHILDREN; LINKAGE; SCALE AB Studies have shown that genetic factors are significant in predisposing individuals to obsessive-compulsive disorder (OCD). Family studies have demonstrated significantly higher rates of OCD in parents and siblings of OCD probands with an age-corrected morbid risk ranging from approximately 10% to 35% in first-degree relatives. Twin studies suggest that this familiality is, in part, due to genetic factors, and results from complex segregation analyses imply the existence of genes that have major effects on the transmission of OCD. However, not all cases of OCD seem to be familial. Furthermore, it appears that even in the familial form, there are clinical and genetic heterogeneities. Thus, future studies should either adjust the prevalence rates used in genetic analyses to account for nonfamilial cases or perform separate analyses of those families with a demonstrably familial form of OCD. Furthermore, in complex psychiatric disorders such as OCD, a single genetic locus may influence only a small part of phenotypic variance, and other genetic and environmental factors may interact in determining clinical phenotype. The implications of this finding on clinical and genetic heterogeneity in OCD are discussed. (C) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA 02114 USA. UAE Univ, Al Ain, U Arab Emirates. UCL, Sch Med, London W1N 8AA, England. RP Pauls, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, 185 Cambridge St, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu NR 45 TC 11 Z9 11 U1 5 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD SEP PY 2006 VL 61 IS 3 BP 359 EP 364 DI 10.1016/j.jpsychores.2006.07.021 PG 6 WC Psychiatry SC Psychiatry GA 083MM UT WOS:000240460000015 PM 16938514 ER PT J AU Conlin, PR Fisch, BM Cavallerano, AA Cavallerano, JD Bursell, SE Aiello, LM AF Conlin, Paul R. Fisch, Barry M. Cavallerano, Anthony A. Cavallerano, Jerry D. Bursell, Sven-Erik Aiello, Lloyd M. TI Nonmydriatic teleretinal imaging improves adherence to annual eye examinations in patients with diabetes SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE adherence; diabetes mellitus; diabetic retinopathy; digital retinal imaging; dilated eye examination; nonmydriatic teleretinal imaging; ocular pathology; rehabilitation; telemedicine; vision ID DIGITAL FUNDUS PHOTOGRAPHY; PRIMARY-CARE; GENERAL-PRACTITIONERS; DIRECT OPHTHALMOSCOPY; COST-EFFECTIVENESS; RETINAL IMAGES; RETINOPATHY; SPECIFICITY; SENSITIVITY; PROGRAM AB We studied whether nonmydriatic digital retinal imaging with remote interpretation (teleretinal imaging) in the ambulatory care setting affected adherence to annual dilated eye examinations among patients with diabetes. We randomly assigned 448 patients to a teleretinal imaging group or a control group. We measured the number of patients who had dilated eye examinations within 12 months of group assignment and the agreement for level of diabetic retinopathy between teleretinal imaging and the eye examinations. The teleretinal imaging group (n = 223) had significantly more dilated eye examinations than the control group (n = 225). Teleretinal imaging and eye examination results showed significant correlation and moderate agreement. Cataract and smaller pupil size were significantly associated with ungradable retinal images. Two-thirds of patients with ungradable images had other ocular findings. Patients reported high satisfaction with nonmydriatic teleretinal imaging. Nonmydriatic teleretinal imaging improves diabetic retinopathy assessment rates. C1 VA Boston Healthcare Syst, Optometry Sect, Boston, MA 02130 USA. Dept Vet Affairs Boston Healthcare Syst, Endocrinol Sect, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA USA. RP Conlin, PR (reprint author), VA Boston Healthcare Syst, Optometry Sect, 151-DIA,150 S Huntington Ave, Boston, MA 02130 USA. EM paul.conlin@med.va.gov FU NIDDK NIH HHS [K24-DK06321] NR 29 TC 20 Z9 21 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2006 VL 43 IS 6 BP 733 EP 739 DI 10.1682/JRRD.2005.07.0117 PG 7 WC Rehabilitation SC Rehabilitation GA 131VJ UT WOS:000243898600004 PM 17310422 ER PT J AU Conlin, PR Fisch, BM Orcutt, JC Hetrick, BJ Darkins, AW AF Conlin, Paul R. Fisch, Barry M. Orcutt, James C. Hetrick, Barbara J. Darkins, Adam W. TI Framework for a national teleretinal imaging program to screen for diabetic retinopathy in Veterans Health Administration patients SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE diabetes; diabetic retinopathy; eye-care delivery; healthcare technology; rehabilitation; screening; telemedicine; teleretinal imaging; VHA; visual impairment ID CARE; PREVALENCE; DIAGNOSIS; RISK; AGE AB Digital retinal imaging with remote image interpretation (teleretinal imaging) is an emerging healthcare technology for screening patients for diabetic retinopathy (DR). The Veterans Health Administration (VHA) convened an expert panel in 2001 to determine and resolve the requisite clinical, quality and training, information technology, and healthcare infrastructure issues associated with deploying a teleretinal imaging system. The panel formulated consensus recommendations based on available literature and identified areas of uncertainty that merited further clarification or research. Subsequent VHA experience with teleretinal imaging and accumulated scientific evidence support nationwide regionalized deployment of teleretinal imaging to screen for DR. The goal is to screen approximately 75,000 patients in the first year of the program, which commenced in 2006. This program will increase patients' access to screening for DR, provide outcomes data, and offer a unique platform for systematically evaluating the role of this technology in the care of diabetic eye disease and routine eye-care practice. C1 VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. Harvard Univ, Sch Med, Boston, MA USA. VA Boston Healthcare Syst, Optometry Sect, Boston, MA USA. VA Puget Sound Hlth Care Syst, Dept Ophthalmol, Seattle, WA USA. Johnathan M Wainwright Mem VA Med Ctr, Optometry Serv, Walla Walla, WA USA. Off Care Coordinat, Vet Htlh Adm, Washington, DC USA. RP Conlin, PR (reprint author), VA Boston Healthcare Syst, Endocrinol Sect, 151-DIA,150 S Huntington Ave, Boston, MA 02130 USA. EM paul.conlin@med.va.gov FU NIDDK NIH HHS [K24-DK06321] NR 16 TC 19 Z9 20 U1 2 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2006 VL 43 IS 6 BP 741 EP 747 DI 10.1682/JRRD.2005.08.0146 PG 7 WC Rehabilitation SC Rehabilitation GA 131VJ UT WOS:000243898600005 PM 17310423 ER PT J AU Iversen, MD Petersson, IF AF Iversen, Maura Daly Petersson, Ingemar F. TI Design issues and priorities in team and nonpharmacological arthritis care research SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT CARE III Conference CY MAY, 2005 CL Toronto, CANADA DE study design; arthritis; team; nonpharmacologic care ID PATIENT SATISFACTION; RHEUMATOID-ARTHRITIS; KNEE ARTHROPLASTY; EXERCISE; SWEDEN; HEALTH; TRIAL AB Nonpharmacologic and team care research present unique design challenges. Nonpharmacologic care by nature is multifaceted and complex. Rarely do patients receive an intervention in isolation. The delivery of a single or group of interventions can be provided by one provider but is frequently provided by teams. Therefore, it is imperative that clinical researchers design studies that evaluate single and multimodal interventions as well as studies that best reproduce the team model of service delivery to accurately examine interventions. While it is well accepted that the research question drives the design, it is imperative to recognize that certain aspects of nonpharmacologic and team care restrict the implementation or effectiveness of specific design components. For example, as patients are required to actively engage in lifestyle changes, double-blinding cannot be employed. In addition, there is no accepted operational definition of team care in arthritis. It is important to keep in mind the characteristics of these interventions in the selection of a research design and develop strategies to best examine these interventions. Combining aspects of randomized controlled trials with qualitative methods is one technique to enrich data collected on these interventions. Certain features of pharmacovigilance studies may also serve as an alternative model. The use of national or regional registries for longterm clinical followup as seen in orthopedic surgery may prove to be applicable in the design of studies for evaluation of team care. Our article will discuss issues related to the design and synthesis of arthritis care research, and the role of patients in the design of clinical trials; describe collaborative international activities furthering team and nonpharmacological arthritis care research; and identify research activities that may influence future practice and the health of people with arthritis. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Phys Therapy, Boston, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sect Clin Sci, Div Rheumatol Allergy & Immunol,Med Sch, Boston, MA 02115 USA. Spenshult Hosp Rheumat Dis, Halmstad, Sweden. Lund Univ, Dept Orthoped, Lund, Sweden. RP Iversen, MD (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Phys Therapy, 36 1st Ave,Charlestown Navy Yard, Boston, MA 02129 USA. EM miversen@partners.org RI iversen, maura/O-5388-2015 OI iversen, maura/0000-0003-4708-9914 NR 23 TC 14 Z9 14 U1 0 U2 1 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 2006 VL 33 IS 9 BP 1904 EP 1907 PG 4 WC Rheumatology SC Rheumatology GA 082HN UT WOS:000240377400040 PM 16960953 ER PT J AU Tingart, MJ Lehtinen, J Zurakowski, D Warner, JJP Apreleva, M AF Tingart, Markus J. Lehtinen, Janne Zurakowski, David Warner, Jon J. P. Apreleva, Maria TI Proximal humeral fractures: Regional differences in bone mineral density of the humeral head affect the fixation strength of cancellous screws SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID SURGICAL NECK FRACTURES; UPPER END AB The purpose of this study was to investigate the 3-dimensional trabecular bone mineral density (BMD) in the humeral head and determine the effects of trabecular BMD on the pullout strength of cancellous screws. Five regions of interest (ROIs) were defined in the humeral head (superior- anterior, superior-posterior, central, inferior-anterior, and inferior-posterior). The trabecular BMD of each ROI was determined by use of peripheral quantitative computed tomography. Cancellous screws were inserted in each ROI and cyclically loaded. The superior-anterior ROI had a lower trabecular BMD than all other ROIs (P <. 001). The central ROI had a higher trabecular BMD than the inferior-anterior ROI (P <. 01), whereas no differences were found between the inferior-posterior, superior-posterior and central ROis. Pullout strength was lower in the superior-anterior ROI compared with all other ROIs (P <. 01). The trabecular BMD and pullout strength were significantly correlated (P <. 01). Placement of screws in regions with a higher trabecular BMD may help to prevent implant loosening and may improve patient outcome. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. RP Apreleva, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. EM Maria.Apreleva@gmx.net NR 13 TC 54 Z9 62 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP-OCT PY 2006 VL 15 IS 5 BP 620 EP 624 DI 10.1016/j.jse.2005.09.007 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 088BB UT WOS:000240785400016 PM 16979060 ER PT J AU Gvilia, I Mcginty, D Szymusiak, R AF Gvilia, I. Mcginty, D. Szymusiak, R. TI Neuronal activation in the preoptic area during different levels of sleep drive SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 18th Congress of the European-Sleep-Research-Society CY SEP 12-16, 2006 CL Innsbruck, AUSTRIA SP European Sleep Res Soc C1 I Beritashvili Inst Physiol, Tbilisi, Rep of Georgia. VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2006 VL 15 SU 1 BP 66 EP 66 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 076NW UT WOS:000239966000157 ER PT J AU Costello, RM AF Costello, Raymond M. TI Long-term mortality from alcoholism: A descriptive analysis SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID FOLLOW-UP; CONSUMPTION; COHORT; MEN AB Objective: Short-term alcoholism mortality studies are limited in their ramifications for long-term, comprehensive treatment program planning. Therefore, this study was pursued for more than 33 years to answer questions such as how, when, and why alcoholics die after discharge from an intermediate care component of a comprehensive community-based treatment program. Method: A cohort of 500 alcoholics admitted in five groups of 100 in the years 1963, 1964, 1967, 1970, and 1972 to an intermediate care unit of a community-based, comprehensive treatment program was tracked for 33-42 years to document deaths. Case-fatality rate (CFR) and cause-specific mortality rate were computed and correlated with follow-up lag and ethnicity. Results: Four hundred and forty nine subjects died within 39 years, with 50% of the deaths occurring by Year 11. Average annual CFR was .057. Cause-specific mortality varied over time and with ethnicity. Deaths attributable to lifestyle causes (i.e., suicide, homicide, accidents, and AIDS) occurred disproportionately in the earlier years of the follow-up, claiming the youngest and ethnic minority (black and Hispanic) persons disproportionately to white. Whites tended to live longer, but all three racial/ethnic groups died of lifestyle causes at young ages, early in the follow-up series, and at relatively older ages from cancer and diseases of the lung late in the follow-up series. Conclusions: Comprehensive treatment programs must prepare for lifestyle crises soon after discharge from intermediate care and for organ diseases later. Ethnicity is a significant predictor of early death in alcoholic cohorts and must be considered in comprehensive treatment program planning. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Kerrville, TX 78028 USA. RP Costello, RM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM costello@uthscsa.edu NR 19 TC 7 Z9 8 U1 1 U2 2 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 2006 VL 67 IS 5 BP 694 EP 699 PG 6 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 068JB UT WOS:000239368700006 PM 16847537 ER PT J AU Mokuno, Y Berthiaume, F Tanimura, Y Yarmush, ML AF Mokuno, Yasuji Berthiaume, Francois Tanimura, Yoko Yarmush, Martin L. TI Heat shock preconditioning inhibits CD4(+) T lymphocyte activation in transplanted fatty rat livers SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE choline- and methionine-deficient diet; gadolinium chloride; CD4(+) T Lymphocytes; neutrophils; interferon-gamma ID ISCHEMIA-REPERFUSION INJURY; NECROSIS-FACTOR-ALPHA; DONOR LIVER; ISCHEMIA/REPERFUSION INJURY; NEUTROPHIL INFILTRATION; INFLAMMATORY RESPONSES; COLD PRESERVATION; WARM ISCHEMIA; IN-VIVO; PATHWAY AB Heat shock preconditioning (HPc) of fatty donor livers significantly increases recipient survival in rats. We investigated to what extent the blockade of Kupffer cells by gadolinium chloride (GdCl3) can mimic the effect of HPc and the involvement of liver CD4(+) T lymphocytes in HPc. Fatty liver was experimentally induced in Lewis rats by a choline-and methionine-deficient diet. Fatty liver donors were pretreated with HPc (42.5 degrees C for 10 min), the Kupffer cell inhibitor GdCl3, or placebo (sham group). Donors were then harvested, stored in University of Wisconsin preservation solution for 12 h at 4 degrees C, and transplanted into normal syngeneic rats. Hepatic injury (alanine aminotransferase) and serum cytokines (interleukin-12p70, tumor necrosis factor-a, and interleukin-10) of recipients increased at 3 h, then decreased, and increased again at 24 h after transplantation. HPc treatment diminished both the early and later phases of this biphasic response and improved recipient survival. GdCl3 reduced these cytokines in the early but not the later phase and did not reduce neutrophil accumulation or improve the recipient survival. HPc, but not GdCI3 treatment, also reduced the number of liver CD4(+) T lymphocytes and their interferon-gamma production. We conclude that HPc, but not GdCl3 treatment, prevents biphasic liver injury and the activation of liver CD4(+) T lymphocytes in transplanted fatty donor livers. (c) 2006 Elsevier Inc. All rights reserved. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM Ireis@sbi.org FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-11, R01DK59766, R01DK43371] NR 43 TC 6 Z9 6 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 2006 VL 135 IS 1 BP 92 EP 99 DI 10.1016/j.jss.2006.02.015 PG 8 WC Surgery SC Surgery GA 079UN UT WOS:000240203500014 PM 16600305 ER PT J AU O'Neill, AC Barbe, L Randolph, MA Berthiaume, F AF O'Neill, Anne C. Barbe, Laurent Randolph, Mark A. Berthiaume, Francois TI Isolated perfusion of a tubed superficial epigastric flap in a rodent model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE perfusion; surgical flaps; skin; metabolism; rat ID PORCINE SKIN FLAP; PERCUTANEOUS-ABSORPTION; CUTANEOUS TOXICOLOGY; INVITRO MODEL; MUSCLE; PROTEIN; METABOLISM; INSULIN; RAT AB Background. Isolated perfusion models can yield important data regarding metabolism of the skin. An effective model must remain stable during perfusion but respond appropriately to metabolic and vascular stimuli. We describe the design and characterization of a tubed superficial epigastric isolated perfusion flap. Materials and methods. Tubed superficial epigastric flaps were created in 20 male Sprague Dawley rats. Forty-eight hours later the femoral vessels were cannulated and the flaps were perfused using a Krebs-Heinseleit buffer containing albumin for a period of 2 h. In five of the flaps norepinephrine and acetylcholine were added sequentially to the perfusate to determine vascular reactivity. In a further four flaps insulin (20 U/liter) and iodoacetate (5 mm) were added to the perfusate to confirm that the flap was metabolically active and reactive. Venous outflow was collected at regular intervals and analyzed for electrolytes, lactate, and glucose content. Vascularity and skin perfusion were characterized using barium microangiography and methylene blue dye injection. Results. This flap model was found to be stable l terms of arterial pressure, electrolyte levels, and lactate production over the perfusion period. Norepinephrine caused a sharp increase in vascular resistance, which was reversed by administration of acetylcholine. Lactate production increased appropriately with the addition of insulin to the perfusate with a rapid decline following addition of the glycolysis inhibitor iodoacetate. There was no leakage of perfusate or significant swelling of the flap during the perfusion. Conclusions. The tubed superficial epigastric artery flap makes an effective model for isolated perfusion studies of the skin with a wide range of experimental applications. (c) 2006 Elsevier Inc. All rights reserved. C1 Shriners Burn Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02115 USA. RP Berthiaume, F (reprint author), Shriners Burn Inst, 51 Blossom St, Boston, MA 02114 USA. EM Francois_Berthiaume@hms.harvard.edu OI Barbe, Laurent/0000-0003-4475-6478 NR 20 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2006 VL 135 IS 1 BP 164 EP 169 DI 10.1016/j.jss.2006.01.032 PG 6 WC Surgery SC Surgery GA 079UN UT WOS:000240203500024 PM 16566940 ER PT J AU Madihally, SV Pantelogianis, A Toner, M AF Madihally, Sundararajan V. Pantelogianis, Angela Toner, Mehmet TI Antiproteolytic action of orally delivered insulin using pH-responsive hydrogels in a rat burn model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE burn injury; oral delivery; insulin; muscle wasting ID MUSCLE PROTEIN-SYNTHESIS; SKELETAL-MUSCLE; THERMAL-INJURY; GLUCOSE; HYPERINSULINEMIA; STIMULATION; METABOLISM; BREAKDOWN; TRAUMA; CELLS AB Subcutaneously delivered small doses of insulin has shown beneficial effects on burn injury-induced muscle wasting and wound healing. To improve the method of insulin treatment for clinical settings, this study investigated the effect of insulin delivered orally using pH-responsive poly(methacrylic-g-ethylene glycol) (P(MAA-g-EG)) hydrogels in a 20% total burn surface area rat burn injury model. P(MAA-g-EG) were synthesized in-house and insulin release characteristics were performed in vitro. Young rats weighing 80-150 g were subjected to 15-20% total body surface area burn injury and treated with insulin-containing hydrogels enclosed in gelatin capsules for 3 days. The dosage was adjusted to match 0.25 U (day 1), 0.5U (day 2), and 1.0 U (day 3) per 100 grams of body weight. All animals were housed in metabolic cages and their physical activity, body weight, food consumption, water uptake, circulating glucose levels, and urinary tyrosine content were monitored for 4 to 15 days after burn. Results show that the orally delivered insulin restored the body weight of burned rats and influenced wound healing, similar to subcutaneous delivery. Measured glucose levels showed significantly less perturbation, suggesting the possibility of increasing the dosage. In conclusion, muscle wasting can be significantly inhibited by the oral administration of insulin using pH-responsive hydrogels. (c) 2006 Elsevier Inc. All rights reserved. C1 Shriners Hosp Children, Boston, MA 02114 USA. Oklahoma State Univ, Sch Chem Engn, Stillwater, OK 74078 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org RI Madihally, Sundararajan/D-9285-2012 OI Madihally, Sundararajan/0000-0001-7498-5760 NR 29 TC 0 Z9 0 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2006 VL 135 IS 1 BP 187 EP 194 DI 10.1016/j.jss.2006.01.029 PG 8 WC Surgery SC Surgery GA 079UN UT WOS:000240203500027 PM 16616764 ER PT J AU Drell, MJ Josephson, A Pleak, R Riggs, P Rosenfeld, A AF Drell, Martin J. Josephson, Allan Pleak, Richard Riggs, Paula Rosenfeld, Alvin TI Clinical problem solving: The case of John, Part I SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 LSU Med Sch, New Orleans Adolescent Hosp & Community Syst Care, Dept Psychiat, Div Infant Child & Adolescent Psychiat, New Orleans, LA 70018 USA. Bingaham Child Guidance Ctr, Louisville, KY USA. Zucker Hillside Hosp, Long Isl Jewish Med Ctr, Div Child & Adolescent Psychiat, Glen Oaks, NY USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Drell, MJ (reprint author), LSU Med Sch, New Orleans Adolescent Hosp & Community Syst Care, Dept Psychiat, Div Infant Child & Adolescent Psychiat, 210 State St, New Orleans, LA 70018 USA. EM mdrell@lsuhsc.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2006 VL 45 IS 9 BP 1124 EP 1131 DI 10.1097/01.chi.0000228130.56956.88 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 078NO UT WOS:000240110700012 PM 16926620 ER PT J AU Kratochvil, CJ Wilens, TE Upadhyaya, H AF Kratochvil, Christopher J. Wilens, Timothy E. Upadhyaya, Himanshu TI Pharmacological management of a youth with ADHD, marijuana use, and mood symptoms SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID SUBSTANCE USE DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CONDUCT DISORDER; ADOLESCENTS; MEDICATIONS; BUPROPION; METHYLPHENIDATE; ADULTS C1 Univ Nebraska, Med Ctr, Dept Psychiat, Omaha, NE 68198 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Kratochvil, CJ (reprint author), Univ Nebraska, Med Ctr, Dept Psychiat, 985581 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ckratoch@unmc.edu NR 18 TC 1 Z9 1 U1 1 U2 3 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 2006 VL 45 IS 9 BP 1138 EP 1141 DI 10.1097/01.chi.0000228126.34085.79 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 078NO UT WOS:000240110700014 PM 16926622 ER PT J AU Anderson, RR AF Anderson, R. Rox TI Commentary: Tattoos and body piercing SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 55 Fruit St,BHX 630, Boston, MA 02114 USA. EM rranderson@partners.org NR 0 TC 8 Z9 8 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2006 VL 55 IS 3 BP 422 EP 422 DI 10.1016/j.jaad.2006.03.027 PG 1 WC Dermatology SC Dermatology GA 077OT UT WOS:000240040200006 PM 16908346 ER PT J AU El Tal, AK Posner, MR Spigelman, Z Ahmed, AR AF El Tal, Abdul Kader Posner, Marshall R. Spigelman, Zachary Ahmed, A. Razzaque TI Rituximab: A monoclonal antibody to CD20 used in the treatment of pemphigus vulgaris SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID INTRAVENOUS IMMUNOGLOBULIN THERAPY; B-CELL THERAPY; MUCOCUTANEOUS BLISTERING DISEASES; CHRONIC LYMPHOCYTIC-LEUKEMIA; AUTOIMMUNE HEMOLYTIC-ANEMIA; ANTI-CD20 ANTIBODY; REFRACTORY PEMPHIGUS; ADJUVANT THERAPY; BONE-MARROW; DISORDERS AB Background: Rituximab is an anti-CD20 chimeric antibody that selectively targets B lymphocytes. Recently, it has been reported to be beneficial in treating pemphigus vulgaris. Objective. Our aim was to review the English-language literature on the treatment of pemphigus vulgaris (PV) with rituximab and to determine its efficacy and influence on clinical outcome(s). Material and methods. A retrospective review of the literature on the use of rituximab in the treatment of PV was conducted. Seventeen patients in 10 reports were described and their data were reviewed. Results: The majority of patients received one course of rituximab along with conventional immunosuppressive therapy as concomitant therapy; 88% of the patients demonstrated improvement. More than half of the patients were followed up for more than 6 months after rituximab treatment; they appeared to be clinically disease free, but were still receiving conventional immunosuppressive therapy. Side effects in most patients were transient and infusion related. Serious infections occurred in 4 patients. One patient died. Limitations: The sample size of this study is small; there is no uniformity of data collection or measurement of key and critical indices, and follow-up was limited. Conclusion. Rituximab may be a promising agent in treatment of PV. C1 New England Baptist Hosp, Ctr Blistering Dis, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Parker Hill Oncol, Boston, MA USA. RP Ahmed, AR (reprint author), New England Baptist Hosp, Ctr Blistering Dis, Dept Med, 70 Parker Hill Ave,Suite 208, Boston, MA 02120 USA. EM arahmedmd@msn.com NR 68 TC 31 Z9 33 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2006 VL 55 IS 3 BP 449 EP 459 DI 10.1016/j.jaad.2006.05.009 PG 11 WC Dermatology SC Dermatology GA 077OT UT WOS:000240040200011 PM 16908351 ER PT J AU Romanoff, MR AF Romanoff, Maria R. TI Assessing military veterans for posttraumatic stress disorder: A guide for primary care clinicians SO JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS LA English DT Article DE posttraumatic stress disorder; veterans; primary care ID HEALTH; PTSD AB Purpose: To educate primary care providers on the physical effects of posttraumatic stress disorder (PTSD), explain why military veterans are at great risk, and describe how to identify PTSD in primary care clients. Data sources: Current scientific and psychiatric literature on PTSD. Conclusions: PTSD is prevalent in the military community because of the frequency and type of trauma seen in the combat zone. With the ongoing military deployments, assessment for the presence of PTSD is increasingly important for comprehensive and high-quality primary care. Clients with trauma histories, such as veterans, are at increased risk for physical disorders such as heart disease and psychological disorders such as anxiety, depression, and PTSD. Implications for practice: Primary care clinicians, including those outside the military health system, are essential in identifying trauma histories and directing clients to appropriate care. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Romanoff, MR (reprint author), 2001 Falls Blvd,314, Quincy, MA 02169 USA. EM mromanoff@partners.org NR 12 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1041-2972 J9 J AM ACAD NURSE PRAC JI J. Am. Acad. Nurse Pract. PD SEP PY 2006 VL 18 IS 9 BP 409 EP 413 DI 10.1111/j.1745-7599.2006.00147.x PG 5 WC Health Care Sciences & Services; Nursing SC Health Care Sciences & Services; Nursing GA 076VX UT WOS:000239987300004 PM 16958771 ER PT J AU Crawford, RS Albadawi, H Atkins, MD Jones, JJ Fink, MP Watkins, MT AF Crawford, Robert S. Albadawi, Hassan Atkins, Marvin D. Jones, John J. Fink, Mitchell P. Watkins, Michael T. TI Ethyl pyruvate prevents ATP depletion and ameliorates inflammation in a murine model of hind-limb ischemia and reperfusion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2006 VL 203 IS 3 SU S BP S105 EP S105 DI 10.1016/j.jamcollsurg.2006.05.276 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800231 ER PT J AU Gray, SH Vick, C Graham, L Finan, K Neumayer, L Catarina, K Hawn, M AF Gray, Stephen H. Vick, Catherine Graham, Laura Finan, Kelly Neumayer, Leigh Catarina, Kiefe Hawn, Mary TI Unplanned enterotomy or bowel resection during elective hernia repair increases complications SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 Univ Alabama, Birmingham VAMC, Birmingham, AL 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 2006 VL 203 IS 3 SU S BP S69 EP S69 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800142 ER PT J AU Kunisaki, SM Sundback, C Krebs, N Ochoa, E Vacanti, J AF Kunisaki, Shaun M. Sundback, Cathryn Krebs, Nicholas Ochoa, Erin Vacanti, Joseph TI Controlled fabrication of engineered small intestinal grafts using polycaprolactone and polyurethane scaffolds SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 Massachusetts Gen Hosp, Wellesley, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2006 VL 203 IS 3 SU S BP S19 EP S19 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800024 ER PT J AU Ochoa, O Shireman, PK McManus, LM AF Ochoa, Oscar Shireman, Paula K. McManus, Linda M. TI Altered inflammation increases intramuscular fat accumulation and impairs skeletal muscle regeneration following ischemic injury in CCR2-/-mice SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 UTHSCSA, S Texas Vet Hlth Care Syst, San Antonio, TX 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 2006 VL 203 IS 3 SU S BP S101 EP S101 DI 10.1016/j.jamcollsurg.2006.05.265 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800221 ER PT J AU Rakhlin, EY Rosow, D Hezel, A Strobel, O Mino-Kenudson, M Stirman, A Mikhailova, E del Castillo, CF Warshaw, A Thayer, S AF Rakhlin, Elena Y. Rosow, David Hezel, Aram Strobel, Oliver Mino-Kenudson, Mari Stirman, Amy Mikhailova, Elaina del Castillo, Carlos Fernandez Warshaw, Andrew Thayer, Sarah TI Sonic hedgehog pathway - a potential target for pancreatic adenocarcinoma treatment SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2006 VL 203 IS 3 SU S BP S46 EP S47 DI 10.1016/j.jamcollsurg.2006.05.120 PG 2 WC Surgery SC Surgery GA 082SF UT WOS:000240406800088 ER PT J AU Sailhamer, E Chen, Z Rhee, P Velmahos, G De Moya, M Alam, H AF Sailhamer, Elizabeth Chen, Zheng Rhee, Peter Velmahos, George De Moya, Marc Alam, Hasan TI Induction of profound hypothermia improves survival in a swine model of complex vascular, splenic and colonic injuries, without an increase in bleeding and septic complications SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Uniformed Serv Univ Hlth Sci, 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 2006 VL 203 IS 3 SU S BP S31 EP S32 DI 10.1016/j.jamcollsurg.2006.05.078 PG 2 WC Surgery SC Surgery GA 082SF UT WOS:000240406800052 ER PT J AU DePaola, D Touger-Decker, R AF DePaola, Dominick Touger-Decker, Riva TI Nutrition and dental medicine: Where is the connection? SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 Forsyth Inst, Boston, MA USA. Univ Med & Dent New Jersey, Dept Diagnost Sci, Div Nutr, Newark, NJ 07103 USA. RP DePaola, D (reprint author), Forsyth Inst, Boston, MA USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2006 VL 137 IS 9 BP 1208 EP 1210 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 086IX UT WOS:000240668100002 PM 16946416 ER PT J AU Friedlander, AH Norman, DC Mahler, ME Norman, KM Yagiela, JA AF Friedlander, Arthur H. Norman, Dean C. Mahler, Michael E. Norman, Keith M. Yagiela, John A. TI Alzheimer's disease - Psychopathology, medical management and dental implications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Review DE dental treatment; Alzheimer's disease ID ADVERSE DRUG-INTERACTIONS; DOUBLE-BLIND; LATE-LIFE; CHOLINESTERASE-INHIBITORS; ASPIRATION PNEUMONIA; ADVANCED DEMENTIA; RISK-FACTORS; ORAL HEALTH; TRIAL; NEURODEGENERATION AB Background. The authors review the clinical features, epidemiology, pathophysiology, medical management, dental findings and dental treatment of patients with Alzheimer's disease (AD). Studies Reviewed. The authors conducted MEDLINE searches for 2000 through 2005 using the terms "Alzheimer's disease," "geriatric," "epidemiology," "pathophy iology," "treatment" and "dentistry." Reports selected for further review included those published in English peer-reviewed journals. The authors gave preference to articles reporting randomized, controlled trials. Results. AD is a progressive and fatal neurodegenerative disorder characterized by cognitive dysfunctions, particularly in learning. and, memory, and the emergence of behavioral abnormalities. Deficiencies in the cells responsible for storage and processing of information underlie the cognitive, functional and behavioral changes seen in, patients with the disorder. Clinical Implications. As the elderly population grows, increasing numbers of Americans with AD will require dental treatment. The prevalence of dental disease likely will be extensive, because of diminished salivary flow and patients' inability to perform appropriate oral hygiene techniques. Preventive dental education for the caregiver and use of saliva substitutes and anticaries agents by the patient are indicated. C1 VA Greater Los Angeles Healthcare Syst, Neurobehav Clin, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Hosp Dent Serv, Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Clin, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 112 TC 27 Z9 29 U1 1 U2 11 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2006 VL 137 IS 9 BP 1240 EP 1251 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 086IX UT WOS:000240668100020 PM 16946428 ER EF