FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fanucchi, MP Fossella, FV Belt, R Natale, R Fidias, P Carbone, DP Govindan, R Raez, LE Robert, F Ribeiro, M Akerley, W Kelly, K Limentani, SA Crawford, J Reimers, HJ Axelrod, R Kashala, O Sheng, SH Schiller, JH AF Fanucchi, Michael P. Fossella, Frank V. Belt, Robert Natale, Ronald Fidias, Panos Carbone, David P. Govindan, Ramaswamy Raez, Luis E. Robert, Francisco Ribeiro, Maria Akerley, Wallace Kelly, Karen Limentani, Steven A. Crawford, Jeffrey Reimers, Hans-Joachim Axelrod, Rita Kashala, Oscar Sheng, Shihong Schiller, Joan H. TI Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN SP Int Assoc Study Lung Canc ID PROTEASOME INHIBITOR BORTEZOMIB; PLATINUM-BASED CHEMOTHERAPY; NON-HODGKINS-LYMPHOMA; SOLID TUMORS; REFRACTORY MYELOMA; INDUCED APOPTOSIS; PLUS CARBOPLATIN; SUPPORTIVE CARE; TRIAL; PS-341 AB Purpose To evaluate the efficacy and toxicity of bortezomib +/- docetaxel as second-line therapy in patients with relapsed or refractory advanced non-small-cell lung cancer (NSCLC). Patients and Methods Patients were randomly assigned to bortezomib 1.5 mg/m(2) ( arm A) or bortezomib 1.3 mg/m(2) plus docetaxel 75 mg/m(2) ( arm B). A treatment cycle of 21 days comprised four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, docetaxel on day 1. Patients could receive unlimited cycles. The primary end point was response rate. Results A total of 155 patients were treated, 75 in arm A and 80 in arm B. Baseline characteristics were comparable. Investigator-assessed response rates were 8% in arm A and 9% in arm B. Disease control rates were 29% in arm A and 54% in arm B. Median time to progression was 1.5 months in arm A and 4.0 months in arm B. One-year survival was 39% and 33%, and median survival was 7.4 and 7.8 months in arms A and B, respectively. Adverse effect profiles were as expected in both arms, with no significant additivity. The most common grade >= 3 adverse events were neutropenia, fatigue, and dyspnea (4% and 53%, 19% and 26%, and 17% and 14% of patients in arms A and B, respectively). Conclusion Bortezomib has modest single-agent activity in patients with relapsed or refractory advanced NSCLC using this schedule, with minor enhancement in combination with docetaxel. Additional investigation of bortezomib in NSCLC is warranted in combination with other drugs known to be active, or using different schedules. C1 Univ Texas SW, Div Hematol Oncol, Dallas, TX 75390 USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. Atlanta Vet Affairs Med Ctr, Decatur, GA USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. DBA Kansas City Canc Ctr, Kansas City Oncol Hematol Grp, Kansas City, MO USA. Washington Univ, Barnard Canc Ctr, St Louis, MO 63130 USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Vanderbilt Univ, Clin Trials Ctr, Nashville, TN USA. Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL USA. Univ Alabama, Birmingham Comprehens Canc Ctr, Birmingham, AL USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. Carolinas Hematol Oncol Associates, Blumenthal Canc Ctr, Charlotte, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Kimmel Canc Ctr Jefferson, Philadelphia, PA USA. RP Schiller, JH (reprint author), Univ Texas SW, Div Hematol Oncol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM joan.schiller@utsouthwestern.edu NR 50 TC 105 Z9 108 U1 1 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 NOV 1 PY 2006 VL 24 IS 31 BP 5025 EP 5033 DI 10.1200/JCO.2006.06.1853 PG 9 WC Oncology SC Oncology GA 102PX UT WOS:000241825900014 PM 17075122 ER PT J AU Hayes, DN Monti, S Parmigiani, G Gilks, CB Naoki, K Bhattacharjee, A Socinski, MA Perou, C Meyerson, M AF Hayes, D. Neil Monti, Stefano Parmigiani, Giovanni Gilks, C. Blake Naoki, Katsuhiko Bhattacharjee, Arindam Socinski, Mark A. Perou, Charles Meyerson, Matthew TI Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID LYMPH-NODE METASTASIS; SMALL-CELL; PULMONARY ADENOCARCINOMA; MOLECULAR CLASSIFICATION; PREDICT SURVIVAL; DATA SETS; CANCER; MICROARRAY; CARCINOMAS; SIGNATURES AB Purpose Published reports suggest that DNA microarrays identify clinically meaningful subtypes of lung adenocarcinomas not recognizable by other routine tests. This report is an investigation of the reproducibility of the reported tumor subtypes. Methods Three independent cohorts of patients with lung cancer were evaluated using a variety of DNA microarray assays. Using the integrative correlations method, a subset of genes was selected, the reliability of which was acceptable across the different DNA microarray platforms. Tumor subtypes were selected using consensus clustering and genes distinguishing subtypes were identified using the weighted difference statistic. Gene lists were compared across cohorts using centroids and gene set enrichment analysis. Results Cohorts of 31, 72, and 128 adenocarcinomas were generated for a total of 231 microarrays, each with 2,553 reliable genes. Three adenocarcinoma subtypes were identified in each cohort. These were named bronchioid, squamoid, and magnoid according to their respective correlations with gene expression patterns from histologically defined bronchioalveolar carcinoma, squamous cell carcinoma, and large-cell carcinoma. Tumor subtypes were distinguishable by many hundreds of genes, and lists generated in one cohort were predictive of tumor subtypes in the two other cohorts. Tumor subtypes correlated with clinically relevant covariates, including stage-specific survival and metastatic pattern. Most notably, bronchioid tumors were correlated with improved survival in early-stage disease, whereas squamoid tumors were associated with better survival in advanced disease. Conclusion DNA microarray analysis of lung adenocarcinomas identified reproducible tumor subtypes which differ significantly in clinically important behaviors such as stage-specific survival. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. MIT, Cambridge, MA 02139 USA. Broad Inst Harvard, Cambridge, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Agilent Technol, Andover, MA USA. Johns Hopkins Univ, Sch Med, Dept Biostat, Baltimore, MD USA. Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Yokohama Municipal Hosp, Yokohama, Kanagawa, Japan. RP Hayes, DN (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295, Chapel Hill, NC 27599 USA. EM hayes@med.unc.edu RI Meyerson, Matthew/E-7123-2012; OI Monti, Stefano/0000-0002-9376-0660; Hayes, D. Neil/0000-0001-6203-7771; Perou, Charles/0000-0001-9827-2247 NR 58 TC 130 Z9 132 U1 1 U2 6 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 NOV 1 PY 2006 VL 24 IS 31 BP 5079 EP 5090 DI 10.1200/JCO.2005.05.1748 PG 12 WC Oncology SC Oncology GA 102PX UT WOS:000241825900020 PM 17075127 ER PT J AU Perlis, RH Baker, RW Zarate, CA Brown, EB Schuh, LM Jamal, HH Tohen, M AF Perlis, Roy H. Baker, Robert W. Zarate, Carlos A., Jr. Brown, Eileen B. Schuh, Leslie M. Jamal, Hassan H. Tohen, Mauricio TI Olanzapine versus risperidone in the treatment of manic or mixed states in bipolar I disorder: A randomized, double-blind trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 156th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 2003 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID RATING-SCALE; 1ST-EPISODE PSYCHOSIS; MEDICATION ALGORITHMS; TEXAS IMPLEMENTATION; DIVALPROEX SODIUM; PLACEBO; HALOPERIDOL; EFFICACY; SAFETY; SCHIZOPHRENIA AB Objective: To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes. Method: This 3-week, randomized, controlled, double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N = 165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM-IV criteria for bipolar I disorder, manic or mixed episode, without psychotic features. The study was conducted at 30 sites in the United States between July 2001 and June 2002. The primary outcome measure was the mean change in the Young Mania Rating Scale (YMRS) total score. Secondary measures included the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions-Bipolar Version (CGI-BP) severity of illness scale, and the Cognitive Test for Delirium (CTD). Quality of life (Short Form Health Survey [SF-12]), psychological well-being (Psychological General Well-Being [PGWB] inventory), and sexual functioning were also compared. Results: Mean modal doses for olanzapine and risperidone were 14.7 mg/day and 3.9 mg/day, respectively. Between treatments, there was no difference in mean change in the YMRS, MADRS, CTD, PGWB, or SF-12 measures or in remission or response rates. Significantly more olanzapine-treated patients completed the study compared with risperidone patients (78.7% vs. 67.0%; p = .019). Olanzapine-treated patients had greater HAM-D-21 (p = .040) and CGI-BP (p = .026) score improvement across the study. Olanzapine-treated patients experienced greater elevations in liver function enzymes (p < .05) and increase in weight (2.5 kg vs. 1.6 kg; p = .004), while risperidone-treated patients were more likely to experience prolactin elevation (51.73 ng/mL vs. 8.23 ng/mL; p < .001) and sexual dysfunction (total score increase of 1.75 vs. 0.64; p = .049). Conclusion: Both olanzapine and risperidone treatment yielded similar improvements in mania. The olanzapine group had significantly greater improvements in secondary measures of severity and depressive symptoms and better study completion rates but experienced more weight gain. C1 Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Lilly Res Labs, Indianapolis, IN USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM rperlis@partners.org NR 42 TC 52 Z9 54 U1 1 U2 2 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 NOV PY 2006 VL 67 IS 11 BP 1747 EP 1753 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 111DT UT WOS:000242432300012 PM 17196055 ER PT J AU Fava, M Graves, LM Benazzi, F Scalia, MJ Iosifescu, DV Alpert, JE Papakostas, GI AF Fava, Maurizio Graves, Lesley M. Benazzi, Franco Scalia, Margaret J. Iosifescu, Dan V. Alpert, Jonathan E. Papakostas, George I. TI A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID EPWORTH SLEEPINESS SCALE; DAYTIME SLEEPINESS AB Background: Antidepressant therapies have been associated with a variety of side effects of both physical and psychological nature. Until recently, however, the majority of the studies focusing on side effects of antidepressants have not routinely included assessment of cognitive side effects. The purpose of the present work is to examine cross-sectionally the prevalence of cognitive and physical side effects of antidepressants during long-term treatment of depression. Method: Patients at least 18 years of age who were deemed responders to antidepressant therapy following at least 3 months of treatment for major depressive disorder (MDD) (diagnosed according to DSM-IV criteria) and whose MDD was considered to be in partial or full remission were eligible for inclusion in this study. Eligible patients were enrolled between January 2003 and December 2004. Study participants were administered the Harvard Department of Psychiatry/National Depression Screening Day (HANDS) scale, the Epworth Sleepiness Scale, the Brief Fatigue Inventory, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), and a study-specific questionnaire inquiring about the emergence of specific side effects such as apathy, fatigue, and inattentiveness. Results: 117 MDD patients (mean +/- SD age: 43.4 +/- 12.6 years; women: N = 78 [66.7%]) met criteria for response according to the HANDS (score < 9). Cognitive symptoms (apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing) were each reported on both the CPFQ and the study-specific questionnaire by more than 30% of the responders on antidepressants. The physical symptoms of fatigue and sleepiness/sedation were reported by over 40% of the responders on both the CPFQ and the study-specific questionnaire. A significant, positive relationship was found between the CPFQ and the severity of residual depressive symptoms as measured by the HANDS total score (F = 15.3, p = .0002). Conclusion: Physical and cognitive symptoms are frequently reported by MDD patients who have responded to antidepressants and are treated in the long term with these agents. It is likely that these symptoms are both side effects of the antidepressants as well as residual symptoms of MDD. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Diego, E Hecker Outpatient Psychiat Ctr, Ctr Collaborat, Ravenna, Italy. RP Fava, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM mfava@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 8 TC 100 Z9 101 U1 0 U2 9 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 NOV PY 2006 VL 67 IS 11 BP 1754 EP 1759 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 111DT UT WOS:000242432300013 PM 17196056 ER PT J AU Otis, JD Macdonald, A Dobscha, SK AF Otis, John D. Macdonald, Alexandra Dobscha, Steven K. TI Integration and coordination of pain management in primary care SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE chronic pain; primary care; disability; distress ID RANDOMIZED-TRIAL; CHRONIC ILLNESS; STEPPED-CARE; HEALTH-CARE; INTERVENTION; MODEL AB Pain is one of the most common symptoms reported to primary care providers and has significant implications for health care costs. The primary aim of this article is to describe and illustrate how to integrate the treatment of chronic pain in the primary care setting. First, we address the integration and coordination of care between mental health and primary care. We then present a typical case and discuss the patient's treatment, outcome, and prognosis. The article concludes with a discussion of issues that frequently arise when integrating psychological treatment for pain in primary care settings. (c) 2006 Wiley Periodicals, Inc. C1 VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. Boston Univ, Boston, MA 02215 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Otis, JD (reprint author), VA Boston Healthcare Syst, Psychol Serv, 116B,150 S Huntington Ave, Boston, MA 02130 USA. EM john.otis@va.gov OI Otis, John/0000-0002-5441-7421 NR 19 TC 4 Z9 4 U1 1 U2 3 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 NOV PY 2006 VL 62 IS 11 BP 1333 EP 1343 DI 10.1002/jclp.20313 PG 11 WC Psychology, Clinical SC Psychology GA 098OY UT WOS:000241533900002 PM 16937344 ER PT J AU Tan, G Alvarez, JA Jensen, MP AF Tan, Gabriel Alvarez, Julie A. Jensen, Mark P. TI Complementary and alternative medicine approaches to pain management SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE pain management; complementary and alternative medicine (CAM); hypnosis; cranial electrotherapy stimulation ID CRANIAL ELECTROTHERAPY STIMULATION; METAANALYSIS; ANALGESIA; HYPNOSIS AB This article argues for and illustrates incorporating complementary and alternative medicine (CAM) interventions into pain treatment plans. Two CAM treatments, cranial electrotherapy stimulation (CES) and self-hypnosis training, are offered in a multidisciplinary pain treatment program. Because these interventions focus on pain relief, they may be of particular interest to patients who have chronic pain who begin treatment with a primary interest in pain reduction. Two cases that illustrate the clinical application of CES and self-hypnosis are presented. When effective, these interventions can help patients have greater confidence in treatments offered by psychologists for pain management and may help make them more open to participating in other psychological interventions that have established efficacy for pain management (e.g., cognitive-behavioral therapy). Because of their brevity, these treatments also can be offered alone to patients who may not have the resources or time to participate in more time-intensive treatment. (c) 2006 Wiley Periodicals, Inc. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Tan, G (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM TAN.GABRIEL@med.va.gov NR 25 TC 5 Z9 7 U1 3 U2 6 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 NOV PY 2006 VL 62 IS 11 BP 1419 EP 1431 DI 10.1002/jclp.20321 PG 13 WC Psychology, Clinical SC Psychology GA 098OY UT WOS:000241533900010 PM 16937354 ER PT J AU Jones, SE Grasruck, M Schmidt, B Madisch, I Egeland, R Brady, T Gupta, R AF Jones, Stephen E. Grasruck, Michael Schmidt, Bernhard Madisch, Ijad Egeland, Ryan Brady, Tom Gupta, Rajiv TI Inherently 3-dimensional method for measurement of computed tomographic resolution anisotropy SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CT; anisotropy; resolution; calibration; flat-panel CT AB Objective: Current techniques to measure computed tomography (CT) spatial resolution use separate methods for in-plane and out-of-plane directions. The growing use of near-isotropic voxel size necessitates a new single method that inherently measures resolution in any direction. Method: We introduce a method using a set of numerous glass microspheres suspended in a small volume from which a mean sphere image is constructed. Projecting asymptotes after imaging different microsphere sets with decreasing diameters provides an inherently 3-dimensional measure of spatial resolution and anisotropy. We apply the method to both a flat-panel and multidetector CT scanner. Results: The full-width at half-maximum from line profiles through mean sphere in transverse directions corresponds to known microsphere diameters. Increased longitudinal full-width at half-maximum corresponds to known anisotropy, which is larger for a multidetector CT scanner than for a flat-panel CT scanner. Conclusions: A new single method to measure CT resolution is inherently isotropic. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Siemens Med Solut, Forchheim, Germany. Harvard Univ, Sch Med, Boston, MA USA. RP Jones, SE (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,55 Fruit St, Boston, MA 02114 USA. EM sejones@partners.org 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 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2006 VL 30 IS 6 BP 962 EP 971 DI 10.1097/01.rct.0000230014.97968.d2 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 104SO UT WOS:000241979500017 PM 17082703 ER PT J AU Gleason, BC Zembowicz, A Granter, SR AF Gleason, Briana C. Zembowicz, Artur Granter, Scott R. TI Non-bullous neutrophilic dermatosis: an uncommon dermatologic manifestation in patients with lupus erythematosus SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID HYDRALAZINE-INDUCED LUPUS; SWEETS-SYNDROME; CUTANEOUS MANIFESTATIONS; URTICARIAL VASCULITIS; LESIONS AB Background: Rare cases of a non-bullous neutrophilic dermatosis occurring in patients with lupus erythematosus (LE) have been reported, often as the presenting manifestation of the disease. Methods: We reviewed hematoxylin and eosin-stained slides and obtained clinical information from four additional patients, two of whom had no prior history of LE. Results: All patients were female, aged 16-59 (mean age 37). Clinically, the skin lesions were characterized by widely distributed pruritic papules and plaques. Three patients presented with systemic symptoms, including fever, arthritis and malaise. Histopathologic examination in all cases showed a superficial perivascular and interstitial neutrophilic infiltrate with leukocytoclasis. There was no evidence of vasculitis. Mild focal vacuolar change was a subtle feature seen only in the biopsies of the two patients with a prior history of LE. Conclusions: It is important to consider LE in the differential diagnosis of non-bullous neutrophilic dermatoses. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Dermatopathol, Dept Pathol, Boston, MA 02115 USA. RP Gleason, BC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM bgleason@partners.org NR 25 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD NOV PY 2006 VL 33 IS 11 BP 721 EP 725 DI 10.1111/j.1600-0560.2006.00559.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 101UC UT WOS:000241765200003 PM 17083690 ER PT J AU Caplan, DJ Chasen, JB Krall, EA Cai, J Kang, S Garcia, RI Offenbacher, S Beck, JD AF Caplan, D. J. Chasen, J. B. Krall, E. A. Cai, J. Kang, S. Garcia, R. I. Offenbacher, S. Beck, J. D. TI Lesions of endodontic origin and risk of coronary heart disease SO JOURNAL OF DENTAL RESEARCH LA English DT Article; Proceedings Paper CT 82nd General Session of the International-Association-for-Dental-Research/American-Association-for-D ental-Research CY MAR 10-13, 2004 CL Honolulu, HI SP Int Assoc Dent Res, Amer Assoc Dent Res DE apical periodontitis; coronary heart disease; epidemiology; inflammation; longitudinal study ID PERIODONTAL-DISEASE; PERIAPICAL LESIONS; CARDIOVASCULAR-DISEASE; TECHNICAL QUALITY; TEETH; OSTEOPOROSIS; ASSOCIATIONS; POPULATIONS; MEDIATORS; BACTERIA AB A paucity of epidemiologic research exists regarding systemic health consequences of endodontic disease. This study evaluated whether incident radiographically evident lesions of endodontic origin were related to development of coronary heart disease (CHD) among 708 male participants in the VA Dental Longitudinal Study. At baseline and every three years for up to 32 years, participants (who were not VA patients) received complete medical and dental examinations, including full-mouth radiographs. Cox regression models estimated the relationship between incident lesions of endodontic origin and time to CHD diagnosis. Among those <= 40 years old, incident lesions of endodontic origin were significantly associated with time to CHD diagnosis (p < 0.05), after adjustment for covariates of interest, with hazard ratios decreasing as age increased. Among those > 40 years old, no statistically significant association was observed. These findings are consistent with research that suggests relationships between chronic periodontal inflammation and the development of CHD, especially among younger men. C1 Univ N Carolina, Dept Dent Ecol, Sch Dent, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Periodontol, Sch Dent, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Caplan, DJ (reprint author), Univ N Carolina, Dept Dent Ecol, Sch Dent, Chapel Hill, NC 27599 USA. EM dan_caplan@dentistry.unc.edu FU NIDCR NIH HHS [K24 DE000419, R01-DE13807, K24-DE00419, R01 DE013807-01A1] NR 29 TC 46 Z9 50 U1 1 U2 10 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 NOV PY 2006 VL 85 IS 11 BP 996 EP 1000 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 098KY UT WOS:000241520600004 PM 17062738 ER PT J AU Franco, GEL Huang, A Camacho, NP Stone, DS Blank, RD AF Franco, G. E. Lopez Huang, A. Camacho, N. Pleshko Stone, D. S. Blank, R. D. TI Increased Young's modulus and hardness of Col1a2(oim) dentin SO JOURNAL OF DENTAL RESEARCH LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res DE collagen type I; dentinogenesis imperfecta; osteogenesis imperfecta; biomechanics; tooth calcification ID COLLAGEN MUTATION DATABASE; OIM MICE EXHIBIT; OSTEOGENESIS IMPERFECTA; DENTINOGENESIS IMPERFECTA; MECHANICAL-PROPERTIES; ELECTRON-MICROSCOPY; BONE; MODEL; DSPP AB Mice harboring the Col1a2(oim) mutation (oim) express dentinogenesis imperfecta. To determine the effect of Col1a2 genotype on tissue mechanical properties, we compared Young's modulus and hardness of dentin in the 3 Col1a2 genotypes. Upper incisors were tested by nanoindentation. Genotype had a significant effect on Young's modulus, but there was not a simple mutant allele dosage relationship. The effect of genotype on hardness did not reach significance. Hardness and Young's modulus were greater near the dento-enamel junction than near the pulp chamber. Greater hardness and Young's modulus values near the dento-enamel junction reflected continued mineralization of the dentin following its initial synthesis. Analysis showed the mechanical data to be consistent with Fourier transform infrared and backscattered electron microscopy studies that revealed increased mineralization in oim bone. Analysis of the data suggests that clinical fragility of teeth in oim mice is not due to deficiencies of hardness or Young's modulus, but may be due to defects in post-yield behavior or resistance to fatigue damage. C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Endocrinol Sect, Madison, WI 53792 USA. Hosp Special Surg, Div Res, New York, NY 10021 USA. Univ Wisconsin, Dept Mat Sci & Engn, Madison, WI 53706 USA. Osteoporosis Res & Clin Ctr, Madison, WI 53705 USA. RP Blank, RD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace, Madison, WI 53705 USA. EM rdb@medicine.wisc.edu RI Stone, Donald/A-7496-2016; Huang, Alice/L-2256-2015 OI Huang, Alice/0000-0002-5037-6829 NR 28 TC 6 Z9 7 U1 0 U2 1 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 NOV PY 2006 VL 85 IS 11 BP 1032 EP 1036 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 098KY UT WOS:000241520600011 ER PT J AU Marsh, RH Brown, DFM Nadel, ES AF Marsh, Regan H. Brown, David F. M. Nadel, Eric S. TI Septic arthritis SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID BACTERIAL ARTHRITIS; INFECTION C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Bulfinch 105, Boston, MA 02114 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2006 VL 31 IS 4 BP 417 EP 420 DI 10.1016/j.jemermed.2006.08.002 PG 4 WC Emergency Medicine SC Emergency Medicine GA 099KG UT WOS:000241592600013 PM 17046485 ER PT J AU Grant, RW Campbell, EG Gruen, RL Ferris, TG Blumenthal, D AF Grant, Richard W. Campbell, Eric G. Gruen, Russell L. Ferris, Timothy G. Blumenthal, David TI Prevalence of basic information technology use by US physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE information technology; physician practice patterns; primary care; academic medicine ID HEALTH-CARE INFORMATION; E-MAIL; ELECTRONIC COMMUNICATION; PATIENT; INTERNET; ATTITUDES; BARRIERS; ADOPTION; SYSTEMS; DIVIDE AB BACKGROUND: Information technology (IT) has been advocated as an important means to improve the practice of clinical medicine. OBJECTIVES: To determine current prevalence of non-electronic health record (EHR) IT use by a national sample of U.S. physicians, and to identify associated physician, practice, and patient panel characteristics. DESIGN, SETTING, AND PARTICIPANTS: Survey conducted in early 2004 of 1,662 U.S. physicians engaged in direct patient care selected from 3 primary care specialties (family practice, internal medicine, pediatrics) and 3 nonprimary care specialties (anesthesiology, general surgery, cardiology). MEASUREMENTS: Self-reported frequency of e-mail communication with patients or other clinicians, online access to continuing medical education or professional journals, and use of any computerized decision support (CDS) during clinical care. Survey results were weighted by specialty and linked via practice zip codes to measures of area income and urbanization. RESULTS: Response rate was 52.5%. Respondents spent 49 (+/- 19) (mean [+/- standard deviation]) hours per week in direct patient care and graduated from medical school 23 (+/- 11) years earlier. "Frequent" use was highest for CDS (40.8%) and online professional journal access (39.0%), and lowest for e-mail communication with patients (3.4%). Ten percent of physicians never used any of the 5 IT tools. In separate logistic regression analyses predicting usage of each of the 5 IT tools, the strongest associations with IT use were primary care practice (adjusted odds ratios [aORs] ranging from 1.34 to 2.26) and academic practice setting (aORs 2.17 to 5.41). Years since medical school graduation (aOR 0.85 to 0.87 for every 5 years after graduation) and solo/2-person practice setting (aORs 0.21 to 0.55) were negatively associated with IT use. Practice location and patient panel characteristics were not independently associated with IT use. CONCLUSIONS: In early 2004, the majority of physicians did not regularly use basic, inexpensive, and widely available IT tools in clinical practice. Efforts to increase the use of IT in medicine should focus on practice-level barriers to adoption. C1 Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Div Gen Med, Boston, MA USA. Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Inst Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Policy & Management, Harvard Sch Publ Hlth, Boston, MA 02115 USA. RP Grant, RW (reprint author), 50-9 Staniford St, Boston, MA 02114 USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452] NR 45 TC 24 Z9 24 U1 3 U2 8 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 NOV PY 2006 VL 21 IS 11 BP 1150 EP 1155 DI 10.1111/j.1525-1497.2006.00571.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 089ZQ UT WOS:000240920800008 PM 16879417 ER PT J AU Volpp, KGM Epstein, AJ Williams, SV AF Volpp, Kevin G. M. Epstein, Andrew J. Williams, Sankey V. TI The effect of market reform on racial differences in hospital mortality SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE quality of health care; economics; medical; financing; organized ID PRICE-COMPETITION; NEW-JERSEY; CARE AB OBJECTIVE: To determine whether racial differences in hospital mortality worsened after implementation of a New Jersey law in 1993 that reduced subsidies for uninsured hospital care and changed hospital payment from rate regulation to price competition. DATA SOURCES/STUDY SETTING: State discharge data for New Jersey and New York from 1990 to 1996. STUDY DESIGN: We used an interrupted time series design to compare risk-adjusted in-hospital mortality rates between states over time. Adjusting for patient characteristics, baseline interstate differences, and common intertemporal trends, we compared the effect sizes for whites and blacks in the following 4 groups: overall, uninsured, insured under age 65, and Medicare patients. DATA COLLECTION/EXTRACTION METHODS: The study sample included 1,357,394 patients admitted to New Jersey or New York hospitals between 1990 to 1996 with stroke, hip fracture, pneumonia, pulmonary embolism, congestive heart failure, or acute myocardial infarction (AMI). PRINCIPAL FINDINGS: The increase in mortality in New Jersey versus New York was significantly larger among blacks than among whites for AMI (2.4% points vs 0.1% points, P-value for difference .026) but not for the other 6 conditions. In groupings of conditions for which hospital admission is non-discretionary and conditions in which admission is discretionary, we found qualitatively larger increases in mortality for blacks but no statistically significant racial differences among patients overall, uninsured patients, insured patients under age 65, or Medicare patients. CONCLUSIONS: Market-based reform and reductions in subsidies for hospital care for the uninsured in New Jersey were associated with worsening racial disparities in in-hospital mortality for AMI but not for 6 other common conditions. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Volpp, KGM (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, 9th Floor,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM volpp70@mail.med.upenn.edu NR 26 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 2006 VL 21 IS 11 BP 1198 EP 1202 DI 10.1111/j.1525-1497.2006.00484.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 089ZQ UT WOS:000240920800018 PM 17026731 ER PT J AU Saha, S AF Saha, Somnath TI The inherent inequities of market-based health care reform SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; RACIAL-DIFFERENCES; MORTALITY; RACE; SEX C1 Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97239 USA. RP Saha, S (reprint author), Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97239 USA. EM sahas@ohsu.edu NR 18 TC 1 Z9 1 U1 1 U2 4 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 NOV PY 2006 VL 21 IS 11 BP 1211 EP 1212 DI 10.1111/j.1525-1497.2006.00618.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 089ZQ UT WOS:000240920800022 PM 17026737 ER PT J AU Almond, CSD Harrington, J Thiagarajan, R Duncan, CN LaPierre, R Halwick, D Blume, ED Del Nido, PJ Neufeld, EJ McGowan, FX AF Almond, Christopher S. D. Harrington, James Thiagarajan, Ravi Duncan, Christine N. LaPierre, Robert Halwick, David Blume, Elizabeth D. Del Nido, Pedro J. Neufeld, Ellis J. McGowan, Francis X. TI Successful use of bivalirudin for cardiac transplantation in a child with heparin-induced thrombocytopenia SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID ACTIVATED CLOTTING TIME; CARDIOPULMONARY BYPASS; HEART-SURGERY; REVERSAL; PATIENT; ANTICOAGULATION; ARGATROBAN; ILOPROST AB Bivalirudin, a direct thrombin inhibitor, has recently emerged as a promising option for anti-coagulation during cardiopulmonary bypass in patients who cannot receive heparin. There is limited experience with the use of bivalirudin in children. We present the case of a child with heparin-induced thrombocytopenia with thrombosis (HIT Type II) who underwent successful orthotopic cardiac transplantation using bivalirudin as the primary anti-coagulant for cardiopulmonary bypass. C1 Childrens Hosp, Dept Cardiol, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesiol, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA. RP Almond, CSD (reprint author), Childrens Hosp, Dept Cardiol, Div Cardiac Crit Care, 300 Longwood Ave, Boston, MA 02215 USA. EM christopher.almond@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011 NR 22 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2006 VL 25 IS 11 BP 1376 EP 1379 DI 10.1016/j.healun.2006.08.005 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 108EC UT WOS:000242222100017 PM 17097505 ER PT J AU Magen, E Yosefy, C Viskoper, RJ Mishal, J AF Magen, E. Yosefy, C. Viskoper, R. J. Mishal, J. TI Treatment of allergic rhinitis can improve blood pressure control SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE allergic; rhinitis; inflammation; CRP ID C-REACTIVE PROTEIN; QUALITY-OF-LIFE; ESSENTIAL-HYPERTENSION; HEALTH; INFLAMMATION; STRESS; INTERLEUKIN-6; POPULATION; PREVALENCE; REDUCTION AB Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure ( BP) control in this population. Sixty-eight subjects of both sexes aged 35 - 60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n = 34) Fluticasone nasal 50 mu g/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n = 34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity ( using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4 +/- 4.3 mm Hg, P = 0.006) and reduction of hs-CRP level (DCRP 2.05 +/- 1.08; P = 0.028) were observed, whereas diastolic BP (DBP) remained unchanged ( DDBP 0.9 +/- 1.7 mm Hg, P = 0.7). There was a significant correlation between DRQLQ and DSBP ( r = 0.86; P = 0.019) and between DCRP and DSBP ( r = 0.56; P = 0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP. C1 Ben Gurion Univ Negev, WHO Collaborat Ctr Prevent CVD, Internal Med B Dept, Ashqelon, Israel. Massachusetts Gen Hosp, Non Invas Cardiac Lab, Boston, MA 02114 USA. RP Magen, E (reprint author), Ben Gurion Univ Negev, WHO Collaborat Ctr Prevent CVD, Internal Med B Dept, Barzilai Med Ctr Campus, Ashqelon, Israel. EM elimgen2@netvision.net.il NR 37 TC 10 Z9 10 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD NOV PY 2006 VL 20 IS 11 BP 888 EP 893 DI 10.1038/sj.jhh.1002088 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 098BD UT WOS:000241494200010 PM 16967045 ER PT J AU Taqueti, VR Grabie, N Colvin, R Pang, H Jarolim, P Luster, AD Glimcher, LH Lichtman, AH AF Taqueti, Viviany R. Grabie, Nir Colvin, Richard Pang, Hong Jarolim, Petr Luster, Andrew D. Glimcher, Laurie H. Lichtman, Andrew H. TI T-bet controls pathogenicity of CTLs in the heart by separable effects on migration and effector activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED MYOCARDITIS; PERIPHERAL-TISSUES; SELECTIN LIGANDS; CELLS; RECEPTOR; CD4(+); IL-12; EXPRESSION; RESPONSES; ACTIVATION AB CD8(+) CTL contribute to the pathogenesis of myocarditis and cardiac allograft rejection. Using a transgenic model of myocarditis, we examined the role of the transcription factor T-bet in the differentiation of pathogenic cardiac Ag-specific CTL. We demonstrate that T-bet-deficient CTL are significantly impaired in their ability to cause disease, despite intact proliferation and activation phenotypes. In the absence of T-bet, there is markedly reduced expression of the chemokine receptor CXCR3, and CXCR3gene knockout CTL are significantly less pathogenic than control CTL. Retroviral-mediated CXCR3 expression in T-bet-deficient CD8(+) T cells reconstitutes their ability to infiltrate but not to damage the heart, establishing that CD8(+) T cell pathogenicity is related to T-bet-dependent CXCR3 expression, reduced cytotoxicity, and enhanced regulation. These findings highlight the potential therapeutic benefit of targeting T-bet-regulated gene expression and CXCR3-dependent migration in immune-mediated heart disease. C1 Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Pathol, Div Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Lichtman, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, NRB-7,Room 752N,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM alichtman@rics.bwh.harvard.edu FU NCI NIH HHS [CA 48126, CA 69212]; NHLBI NIH HHS [HL 072056]; NIAID NIH HHS [AI 059610, AI 56296]; NIDDK NIH HHS [DK 074449] NR 34 TC 36 Z9 36 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 NOV 1 PY 2006 VL 177 IS 9 BP 5890 EP 5901 PG 12 WC Immunology SC Immunology GA 097VN UT WOS:000241477400017 PM 17056513 ER PT J AU Fragoso, RC Pyarajan, S Irie, HY Burakoff, SJ AF Fragoso, Ruben C. Pyarajan, Saiju Irie, Hanna Yoko Burakoff, Steven J. TI A CD8/Lck transgene is able to drive thymocyte differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; PROTEIN-TYROSINE KINASE; CD8 BETA-CHAIN; POSITIVE SELECTION; NEGATIVE SELECTION; MICE LACKING; CYTOPLASMIC DOMAIN; MONOCLONAL-ANTIBODIES; CORECEPTOR FUNCTION; THYMIC MATURATION AB Efficient development of thymocytes requires participation of a CD8 or CD4 coreceptor in the TCR:MHC interaction. Both CD8 and CD4 coreceptor cytoplasmic domains associate with Lck. In this study, we attempted to delineate the role of CD8 alpha-associated Lck in driving CD8 single positive (SP) thymocyte development. We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8 alpha fused to full-length Lck. In mice deficient for CD8a and transgenic for 2C, a MHC class I-restricted TCR, robust reconstitution of CD8 SP thymocytes occurred both centrally and peripherally. The reconstituted CD8 SP population was phenotypically and functionally comparable to 2C wild-type counterparts expressing endogenous CD8a. A CD8 alpha/Lck kinase-dead chimera also resulted in reconstitution of CD8 SP thymocytes. Our results suggest that CD8a-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CD8 SP development may not necessarily depend on Lck kinase activity. C1 Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Sch Med, Inst Canc, Dept Pathol, New York, NY 10003 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burakoff, SJ (reprint author), Skirball Inst Biomol Med, 540 1st Ave,Floor 5,Lab 1, New York, NY 10016 USA. EM burakoff@saturn.med.nyu.edu FU NIAID NIH HHS [AI 17258] NR 44 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2006 VL 177 IS 9 BP 6007 EP 6017 PG 11 WC Immunology SC Immunology GA 097VN UT WOS:000241477400029 PM 17056525 ER PT J AU Dunn, IS Andreucci, A Rose, LB Haggerty, TJ Lawler, M Durda, PJ Kurnick, JT AF Dunn, Ian S. Andreucci, Amy Rose, Lenora B. Haggerty, Timothy J. Lawler, Matthew Durda, Paul J. Kurnick, James T. TI Role of NFAT transcription factors in regulation of melanocytic antigen genes in a subset of melanomas SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 CytoCure LLC, Beverly, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 664 EP 664 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900126 ER PT J AU Mempel, T AF Mempel, Thorsten TI Regulatory T cells reversibly suppress cytolytic function, but not effector differentiation, of tumor-reactive CD8 T cells in tumor-draining lymph nodes SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 21st Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 26-29, 2006 CL Los Angeles, CA C1 Harvard Med Sch, CBR Inst Biomed Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2006 VL 29 IS 6 BP 667 EP 667 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 099CK UT WOS:000241569900136 ER PT J AU Prather, P Thiele, E de Vries, PJ AF Prather, P. Thiele, E. de Vries, P. J. TI Neuropsychological profiling in tuberous sclerosis complex (TSC): Implications for neurobiology and clinical interventions SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Meeting Abstract DE tuberous sclerosis complex; executive control processes; neuropsychological profile C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cambridge, Dev Psychiat Sect, Cambridge, England. 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 0964-2633 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD NOV PY 2006 VL 50 BP 788 EP 788 PN 11 PG 1 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 087WM UT WOS:000240773500024 ER PT J AU Blackard, JT Kang, MH Sherman, KE Koziel, MJ Peters, MG Chung, RT AF Blackard, Jason T. Kang, Minhee Sherman, Kenneth E. Koziel, Margaret James Peters, Marion G. Chung, Raymond T. CA AIDS Clinical Trials Grp A5071 TI Effects of HCV treatment on cytokine expression during HCV/HIV coinfection SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID CHRONIC HEPATITIS-C; NECROSIS-FACTOR-ALPHA; INTERFERON-ALPHA; INTRAHEPATIC EXPRESSION; SUSTAINED RESPONSE; VIRUS-INFECTION; THERAPY; SERUM; RIBAVIRIN; PREDICTORS AB There is growing evidence that cytokine expression is linked to hepatitis C virus (HCV) pathogenesis and treatment response rates among HCV-monoinfected persons. However, because of the profound effects of human immunodeficiency virus (HIV) coinfection on HCV, it is not clear if these observations are also true for HCV/HIV-coinfected individuals. Serum expression of the proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) and the fibrogenic cytokine transforming growth factor-beta 1 (TGF-beta 1) were measured in HCV/HIV-coinfected persons at baseline and at week 24 of HCV therapy. Higher levels of IL-8 and TGF-beta were demonstrated among nonwhite subjects at baseline. Increases in TNF-alpha and IL-8 expression were found at week 24 of HCV therapy, suggesting that enhanced proinflammatory cytokine production may occur during HCV treatment. However, cytokine levels were not predictive of HCV virologic, biochemical, or histologic response. Although previous studies conducted among HCV-monoinfected individuals have suggested that cytokine levels could predict the virologic response to therapy, no such associations were observed among HCV/HIV-coinfected persons, suggesting that they may respond differently to treatment than do their HCV-monoinfected counterparts. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat & AIDS Res, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID NIH HHS [U01 AI069502, P30 AI042851, U01 AI038858, U01 AI038855] NR 19 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD NOV PY 2006 VL 26 IS 11 BP 834 EP 838 DI 10.1089/jir.2006.26.834 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 108AC UT WOS:000242211100007 PM 17115902 ER PT J AU Rosman, J Shapiro, MD Hanon, S AF Rosman, Jonathan Shapiro, Michael D. Hanon, Sam TI Pneumomediastinum and right sided pneumothorax following dual chamber-ICD implantation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE atrial lead perforation; contralateral pneumothorax; pneumomediastinum ID PERMANENT PACEMAKER IMPLANTATION; PNEUMOPERICARDIUM; LEAD C1 Beth Israel Med Ctr, Dept Cardiol, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Cardiac Imaging, Boston, MA 02114 USA. RP Hanon, S (reprint author), Beth Israel Med Ctr, Dept Cardiol, 1st Ave & 16th St,Baird Hall,5th Floor, New York, NY 10003 USA. EM shanon@chpnet.org NR 5 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD NOV PY 2006 VL 17 IS 2 BP 157 EP 158 DI 10.1007/s10840-006-9080-y PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 147MK UT WOS:000245006900011 PM 17323129 ER PT J AU Yang, G Zhang, GQ Pittelkow, MR Ramoni, M Tsao, H AF Yang, Guang Zhang, Guoqi Pittelkow, Mark R. Ramoni, Marco Tsao, Hensin TI Expression profiling of UVB response in melanocytes identifies a set of p53-target genes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; CULTURED HUMAN MELANOCYTES; WNT ANTAGONIST DICKKOPF-1; HUMAN-MELANOMA CELLS; INDUCED DNA-DAMAGE; ULTRAVIOLET-B; HUMAN KERATINOCYTES; HUMAN SKIN; INDUCED PHOSPHORYLATION; ADHESION MOLECULE AB Epidermal melanocytes execute specific physiological programs in response to UV radiation (UVR) at the cutaneous interface. Many melanocytic responses, including increased dendrite formation, enhanced melanogenesis/melanization, and cell cycle arrest impact the ability of melanocytes to survive and to attenuate the UVR insult. Although some of the molecules that underlie these UVR programs are known, a coherent view of UVR-induced transcriptional changes is lacking. Using primary melanocyte cultures, we assessed for UVR-mediated alterations in over 47,000 transcripts using Affymetrix Human Genome U133 Plus 2.0 microarrays. From the 100 most statistically robust changes in transcript level, there were 84 genes that were suppressed > 2.0-fold by UVR; among these transcripts, the identities of 48 of these genes were known. Similarly, there were 99 genes that were induced > 2.0-fold by UVR; the identity of 57 of these genes were known. We then subjected these top 100 changes to the Ingenuity Pathway analysis program and identified a group of p53 targets including the cell cycle regulator CDKN1A (p21CIP), the WNT pathway regulator DKK1 (dickkopf homolog 1), the receptor tyrosine kinase EPHA2, growth factor GDF15, ferrodoxin reductase (FDXR), p53-inducible protein TP53I3, transcription factor ATF3, DNA repair enzyme DDB2, and the beta-adrenergic receptor ADBR2. These genes were also found to be consistently elevated by UVR in six independent melanocyte lines, although there were interindividual variations in magnitude. WWOX, whose protein product interacts and regulates p53 and p73, was found to be consistently suppressed by UVR. There was also a subgroup of neurite/axonal developmental genes that were altered in response to UVR, suggesting that melanocytic and neuronal arborization may share similar mechanisms. When compared to melanomas, the basal levels of many of these p53-responsive genes were greatly dysregulated. Three genes - CDKN1A, DDB2 and ADRB2 - exhibited a trend towards loss of expression in melanomas thereby raising the possibility of a linked role in tumorigenesis. These expression data provide a global view of UVR-induced changes in melanocytes and, more importantly, generate novel hypotheses regarding melanocyte physiology. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. Mayo Clin, Dept Dermatol, Rochester, MN USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 79 TC 58 Z9 61 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2006 VL 126 IS 11 BP 2490 EP 2506 DI 10.1038/sj.jid.5700470 PG 17 WC Dermatology SC Dermatology GA 096EG UT WOS:000241359600019 PM 16888633 ER PT J AU Ancuta, P Wang, JB Gabuzda, D AF Ancuta, Petronela Wang, Jianbin Gabuzda, Dana TI CD16(+) monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE vascular injury; chemokines; CX3CR1; neurotoxicity; neurogeneration ID CEREBROSPINAL-FLUID LEVELS; CENTRAL-NERVOUS-SYSTEM; NECROSIS FACTOR-ALPHA; DENDRITIC CELLS; CHEMOKINE RECEPTOR; BLOOD MONOCYTES; AIDS DEMENTIA; MATRIX METALLOPROTEINASES; FRACTALKINE CX3CL1; EXPRESSION AB The CD16(+) subset of peripheral blood monocytes (Mo) is expanded dramatically during inflammatory conditions including sepsis, HIV-1 infection, and cancer. CD16(+) express high levels of CX3CR1, which mediates arrest onto CX3CL1-expressing endothelial cells (EC) under flow conditions. In contrast, attachment of CD16(-) Mo onto cytokine-activated EC is independent of CX3CL1. Here, we investigate the ability of CD16(+) and CD16(-) Mo to produce proinflammatory cytokines upon interaction with CX3CL1-expressing HUVEC. We demonstrate that CD16(+) but not CD16(-) Mo produce high levels of IL-6, CCL2, and matrix metalloproteinase (MMP)-9 when cocultured with TNF/IFN-gamma-activated HUVEC or nonactivated HUVEC expressing CX3CL1. Furthermore, supernatants from Mo cocultured with cytokine-activated HUVEC induce neuronal death in vitro. These results suggest that membrane-bound CX3CL1 stimulates production of IL-6, CCL2, and MMP-9 by CD16(+) Mo, likely via engagement of CX3CR1. Thus, expansion of CD16(+) Mo and their accumulation onto CX3CL1-expressing EC may result in recruitment of Mo and T cell subsets at sites of inflammation in response to CCL2, IL-6-induced cell activation and/or differentiation, and MMP-9-mediated vascular and tissue injury. J. Leukoc. Biol. 80: 1156-1164; 2006. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 816, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIDA NIH HHS [DA016549]; NINDS NIH HHS [NS35734] NR 76 TC 67 Z9 68 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2006 VL 80 IS 5 BP 1156 EP 1164 DI 10.1189/jlb.0206125 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MJ UT WOS:000243016100021 PM 17056766 ER PT J AU Brundert, M Heeren, J Bahar-Bayansar, M Ewert, A Moore, KJ Rinninger, F AF Brundert, May Heeren, Joerg Bahar-Bayansar, Mukaddes Ewert, Anne Moore, Kathryn J. Rinninger, Franz TI Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI SO JOURNAL OF LIPID RESEARCH LA English DT Article DE high density lipoprotein; scavenger receptor class B type I; reverse cholesterol transport ID HIGH-DENSITY-LIPOPROTEIN; RECEPTOR-CLASS-B; ATHEROSCLEROTIC LESION DEVELOPMENT; MARROW-DERIVED CELLS; SCAVENGER RECEPTOR; LIPID TRANSFER; KNOCKOUT MOUSE; METABOLISM; MICE; FIBROBLASTS AB Scavenger receptor classBtype I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) and facilitates the efflux of unesterified cholesterol. SR-BI expression in macrophages presumably plays a role in atherosclerosis. The role of SR-BI for selective CE uptake and cholesterol efflux in macrophages was explored. Macrophages and HDL originated from wild-type (WT) or SR-BI knockout (KO; homozygous) mice. For uptake, macrophages were incubated in medium containing I-125-/H-3-labeled HDL. For lipid removal, [H-3] cholesterol efflux was analyzed using HDL as acceptor. Selective uptake of HDL CE ([H-3] cholesteryl oleyl ether-I-125-tyramine cellobiose) was similar in WT and SR-BI KO macrophages. Radiolabeled SR-BI KO-HDL yielded a lower rate of selective uptake compared with WT-HDL in WT and SR-BI KO macrophages. Cholesterol efflux was similar in WT and SR-BI KO cells using HDL as acceptor. SR-BI KO-HDL more efficiently promoted cholesterol removal compared with WT-HDL from both types of macrophages. Macrophages selectively take up HDL CE independently of SR-BI. Additionally, in macrophages, there is substantial cholesterol efflux that is not mediated by SR-BI. Therefore, SR-BI-independent mechanisms mediate selective CE uptake and cholesterol removal. SR-BI KO-HDL is an inferior donor for selective CE uptake compared with WT-HDL, whereas SR-BI KO-HDL more efficiently promotes cholesterol efflux. C1 Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rinninger, F (reprint author), Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. EM rinninger@uke.uni-hamburg.de OI Moore, kathryn/0000-0003-2505-2547 NR 43 TC 26 Z9 26 U1 0 U2 0 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 NOV PY 2006 VL 47 IS 11 BP 2408 EP 2421 DI 10.1194/jlr.M600136-JLR200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KI UT WOS:000241667300007 PM 16926440 ER PT J AU Simon, JH Zhang, S Laidlaw, DH Miller, DE Brown, M Corboy, J Bennett, J AF Simon, Jack H. Zhang, Song Laidlaw, David H. Miller, David E. Brown, Mark Corboy, John Bennett, Jeffrey TI Identification of fibers at risk for degeneration by diffusion tractography in patients at high risk for MS after a clinically isolated syndrome SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE multiple sclerosis; diffusion; tractography; neuronal degeneration; MRI; inflammation; Wallerian degeneration ID APPEARING WHITE-MATTER; REMITTING MULTIPLE-SCLEROSIS; CORPUS-CALLOSUM; WALLERIAN DEGENERATION; AXONAL LOSS; ATROPHY; LESIONS; DAMAGE; TRACT; MRI AB Purpose: Focal inflammatory/demyelinating lesions are thought to be the source of Wallerian degeneration or other injury to local, transiting fiber tracts in the brain or spinal cord in multiple sclerosis (MS). A methodology is established to isolate connections between focal demyelinating lesions and intersecting fibers to permit explicit analyses of the pathology of secondary fiber injury distant from the focal lesion. Materials and Methods: A strategy is described and feasibility demonstrated in three patients with a clinically isolated syndrome and positive MRI (at high risk for MS). The strategy utilizes streamtube diffusion tractography to identify neuronal fibers that intersect a focal lesion and pass through a region of interest, in this case the corpus callosum, where distal (to focal lesion) interrogation can be accomplished. Results: A sizeable fraction of the normal appearing white matter (NAWM) in the early stages of disease can be defined in the corpus callosum, which is distinctive in that this tissue connects to distant demyelinating lesions. Conclusion: The new class of tissue called fibers-at-risk for degeneration (FAR) can be identified and interrogated by a variety of quantitative MRI methodologies to better understand neuronal degeneration in MS. C1 Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Brown Univ, Dept Comp Sci, Providence, RI 02912 USA. Univ Colorado, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Dept Ophthalmol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Neurol, Denver, CO USA. RP Simon, JH (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Radiol, Box A-034,4200 E 9th Ave, Denver, CO 80262 USA. EM jack.simon@uchsc.edu NR 23 TC 15 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2006 VL 24 IS 5 BP 983 EP 988 DI 10.1002/jmri.20719 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 100DS UT WOS:000241648400004 PM 17024655 ER PT J AU Lorenz, C Benner, T Chen, PJ Lopez, CJ Ay, H Zhu, MW Menezes, NM Aronen, H Karonen, J Liu, YW Nuutinen, J Sorensen, AG AF Lorenz, Cory Benner, Thomas Chen, Poe Jou Lopez, Chloe Joan Ay, Hakan Zhu, Ming Wang Menezes, Nina M. Aronen, Hannu Karonen, Jari Liu, Yawu Nuutinen, Juho Sorensen, A. Gregory TI Automated perfusion-weighted MRI using localized arterial input functions SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; perfusion-weighted; stroke assessment; cerebral blood flow; arterial input function ID CEREBRAL-BLOOD-FLOW; QUANTIFICATION; STROKE AB Purpose: To investigate the utility of an automated perfusion-weighted MRI (PWI) method for estimating cerebral blood flow (CBF) based on localized arterial input functions (AIFs) as compared to the standard method of manual global AIF selection, which is prone to deconvolution errors due to the effects of delay and dispersion of the contrast bolus. Materials and Methods: Analysis was performed on spin and gradient-echo EPI images from 36 stroke patients. A local AIF algorithm created an AIF for every voxel in the brain by searching out voxels with the lowest delay and dispersion, and then interpolating and spatially smoothing them for continuity. A generalized linear model (GLM) for predicting tissue outcome, and MTT lesion volumes were used to quantify the performance of the localized AIF method in comparison with global methods using ipsilateral and contralateral AIFs. Results: The algorithm found local AlFs in each case without error and generated a higher area under the receiver operating characteristic (ROC) curve compared to both global-AIF methods. Similarly, the local MTT lesion volumes had the least mean squared error (MSE). Conclusion: Automated CBF calculation using local AIFs is feasible and appears to produce more useful CBF maps. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard MIT, Div Hlth Sci & Technol, Charlestown, MA USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Univ Helsinki, Cent Hosp, Funct Brain Imaging Unit, Helsinky Brain Res Ctr, Helsinki, Finland. Finnish Def Forces, Ctr Mil Med, Helsinki, Finland. Univ Turku, Dept Diagnost Radiol, Turku, Finland. RP Sorensen, AG (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41RR14075]; NINDS NIH HHS [NS38477] NR 17 TC 25 Z9 25 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2006 VL 24 IS 5 BP 1133 EP 1139 DI 10.1002/jmri.20717 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 100DS UT WOS:000241648400024 PM 16969793 ER PT J AU Garcia, A Xu, SL Dewhirst, FE Nambiar, PR Fox, JG AF Garcia, Alexis Xu, Shilu Dewhirst, Floyd E. Nambiar, Prashant R. Fox, James G. TI Enterohepatic Helicobacter species isolated from the ileum, liver and colon of a baboon with pancreatic islet amyloidosis SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID CHOLESTEROL GALLSTONE FORMATION; DIABETES-MELLITUS; PYLORI INFECTION; CHRONIC COLITIS; RHESUS-MONKEYS; SP-NOV; CINAEDI; MICE; HEPATICUS; IDENTIFICATION AB Microaerobic bacteria were isolated from a baboon with pancreatic islet amyloidosis and hepatitis. Phenotypic and molecular analyses identified two distinct helicobacters. Analyses of 16S rRNA demonstrated 'Helicobacter macacae' in the ileum and liver, and Helicobacter cinaedi in the colon. To the best of the authors' knowledge, this is the first report describing the isolation of enterohepatic Helicobacter species from a baboon. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Garcia, A (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM agarcia@mit.edu FU NCI NIH HHS [P01 CA 26731, R01 CA 67529]; NCRR NIH HHS [T32 RR 07036]; NIAID NIH HHS [R01 AI 50952]; NIDCR NIH HHS [R01 DE 10374]; NIEHS NIH HHS [P30 ES002109, P30 ES 02109] NR 36 TC 12 Z9 12 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD NOV PY 2006 VL 55 IS 11 BP 1591 EP 1595 DI 10.1099/jmm.0.46707-0 PG 5 WC Microbiology SC Microbiology GA 104BN UT WOS:000241931000019 PM 17030922 ER PT J AU Pyo, RT Sui, JL Dhume, A Palomeque, J Blaxall, BC Diaz, G Tunstead, J Logothetis, DE Hajjar, RJ Schecter, AD AF Pyo, Robert T. Sui, Jinliang Dhume, Ashwini Palomeque, Julieta Blaxall, Bums C. Diaz, George Tunstead, James Logothetis, Diomedes E. Hajjar, Roger J. Schecter, Alison D. TI CXCR4 modulates contractility in adult cardiac myocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE calcium; chemokines; chemokine receptors; contractility; CXCL12; CXCR4; SDF ID CONGESTIVE-HEART-FAILURE; NECROSIS-FACTOR-ALPHA; SARCOPLASMIC-RETICULUM CA2+-ATPASE; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTOR CXCR4; MYOCARDIAL-INFARCTION; VENTRICULAR MYOCYTES; TRANSGENIC MICE; GENE-TRANSFER; STEM-CELLS AB The inflammatory response is critical to the development and progression of heart failure. Chemokines and their receptors are a distinct class of inflammatory modulators that may play a role in mediating myocardial dysfunction in heart failure. Levels of the chemokine CXCL12, also known as stromal cell-derived factor (SDF), and its receptor, CXCR4, are elevated in patients with heart failure, and we undertook this study to determine whether this chemokine system can directly affect cardiac function in the absence of leukocytes. Murine papillary muscles and adult rat cardiac myocytes treated with CXCL12, the only identified ligand of CXCR4, demonstrate blunted inotropic responses to physiologic concentrations of calcium. The negative inotropic effects on cardiac myocytes are accompanied by a proportional diminution of calcium transients. The effects are abrogated by AMD3100, a specific CXCR4 inhibitor. Overexpression of the receptor through adenoviral infection with a CXCR4 construct accentuates the negative inotropic effects of CXCL12 on cardiac myocytes during calcium stimulation. CXCR4 activation also attenuates beta-adrenergic-mediated increases in calcium mobilization and fractional shortening in cardiac myocytes. In electrophysiologic studies, CXCL12 decreases forskolin- and isoproterenol-induced voltage-gated L-type calcium channel activation. These studies demonstrate that activation of CXCR4 results in a direct negative inotropic modulation of cardiac myocyte function. The specific mechanism of action involves alterations of calcium channel activity on the membrane. The presence of functional CXCR4 on cardiac myocytes introduces a new target for treating cardiac dysfunction. (c) 2006 Elsevier Inc. All rights reserved. C1 Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Genet, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Cardiovasc Res Inst, Rochester, NY USA. RP Schecter, AD (reprint author), Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, Box 1030,1 Gustave L Levy Pl, New York, NY 10029 USA. EM alison.schecter@mssm.edu FU NHLBI NIH HHS [R01 HL073458, P50 HL054469, HL078691, HL071763, HL054469, R01 HL073458-04, R01 HL071763, HL057623, R01 HL078691, HL073458] NR 51 TC 49 Z9 49 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 2006 VL 41 IS 5 BP 834 EP 844 DI 10.1016/j.yjmcc.2006.08.008 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 111EW UT WOS:000242435200012 PM 17010372 ER PT J AU Ogino, S Kawasaki, T Kirkner, GJ Loda, M Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Kirkner, Gregory J. Loda, Massimo Fuchs, Charles S. TI CpG island methylator phenotype-low (CIMP-Low) in colorectal cancer: Possible associations with male sex and KRAS mutations SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID DNA METHYLATION; MICROSATELLITE INSTABILITY; BRAF MUTATION; COLON-CANCER; HYPERMETHYLATION; PATTERNS; TUMORS; ADENOCARCINOMA; CARCINOMA; PROFILES AB The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation seems to be a distinct epigenotype of colorectal cancer. However, no study has comprehensively examined features of colorectal cancer with less extensive promoter methylation (designated as "CIMP-low"). Using real-time polymerase chain reaction (MethyLight), we quantified DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1] in 840 relatively unbiased, population-based colorectal cancer samples, obtained from two large prospective cohort studies. CIMP-low (defined as 1/5 to 3/5 methylated promoters) colorectal cancers were significantly more common among men (38 versus 30% in women, P = 0.01) and among KRAS-mutated tumors (44 versus 30% in KRAS/BRAF wild-type tumors, P = 0.0003; 19% in BRAF-mutated tumors, P < 0.0001). In addition, KRAS mutations were significantly more common in CIMP-low tumors (47%) than in CIMP-high tumors (with >= 4/5 methylated promoters, 12%, P < 0.0001) and CIMP-0 tumors (with 0/5 methylated promoters, 37%, P = 0.007). The associations of CIMP-low tumors with male sex and KRAS mutations still existed after tumors were stratified by microsatellite instability status. In conclusion, CIMP-low colorectal cancer is associated with male sex and KRAS mutations. The hypothesis that CMIP-low tumors are different from CIMP-high and CIMP-0 tumors needs to be tested further. C1 Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA055075, P01 CA087969, P01CA55075-13, P01CA87969-03] NR 33 TC 190 Z9 192 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2006 VL 8 IS 5 BP 582 EP 588 DI 10.2353/j.moldx.2006.060082 PG 7 WC Pathology SC Pathology GA 102LF UT WOS:000241811800010 PM 17065427 ER PT J AU Wu, D Takahashi, H Lindeman, N Harris, NL Pinkus, GS Longtine, J Shipp, M Kutok, JL AF Wu, D. Takahashi, H. Lindeman, N. Harris, N. L. Pinkus, G. S. Longtine, J. Shipp, M. Kutok, J. L. TI No evidence for V617F JAK2 mutation in primary mediastinal large B-cell lymphoma (primary tumors and cell lines) and Hodgkin lymphoma (cell lines) SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 16-19, 2006 CL Orlando, FL SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2006 VL 8 IS 5 BP 635 EP 635 PG 1 WC Pathology SC Pathology GA 102LF UT WOS:000241811800073 ER PT J AU Finberg, KE Eversley, JS Rosenberg, ES AF Finberg, K. E. Eversley, J. S. Rosenberg, E. S. TI Evaluation of Invader (R) HCV genotyping ASRs in a clinical microbiology laboratory SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 16-19, 2006 CL Orlando, FL SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2006 VL 8 IS 5 BP 645 EP 645 PG 1 WC Pathology SC Pathology GA 102LF UT WOS:000241811800114 ER PT J AU Ogino, S Kawasaki, T Loda, M Fuchs, C AF Ogino, S. Kawasaki, T. Loda, M. Fuchs, C. TI Down-regulation of p21 (CDKN1A/CIP1) in colorectal cancer is inversely associated with MS1 and CpG island methylator phenotype (CIMP) determined by quantitative DNA methylation analysis SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 16-19, 2006 CL Orlando, FL SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2006 VL 8 IS 5 BP 657 EP 657 PG 1 WC Pathology SC Pathology GA 102LF UT WOS:000241811800165 ER PT J AU Finberg, KE Batten, J Han, M Beheshti, J Mark, EJ Iafrate, AJ AF Finberg, K. E. Batten, J. Han, M. Beheshti, J. Mark, E. J. Iafrate, A. J. TI Mucinous differentiation predicts the presence of KRAS mutation and the absence of EGFR mutation in pulmonary adenocarcinomas with bronchioloalveolar features SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 16-19, 2006 CL Orlando, FL SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2006 VL 8 IS 5 BP 661 EP 662 PG 2 WC Pathology SC Pathology GA 102LF UT WOS:000241811800184 ER PT J AU Li, LQ Boussiotis, VA AF Li, Lequn Boussiotis, Vassiliki A. TI Physiologic regulation of central and peripheral T cell tolerance: lessons for therapeutic applications SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE immunologic tolerance; T cell; B cell; autoimmunity ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; MULTIORGAN TISSUE DESTRUCTION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSCRIPTION FACTOR FOXP3; E3 UBIQUITIN LIGASE; DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSE; NEGATIVE REGULATION AB Immunologic tolerance is a state of unresponsiveness that is specific for a particular antigen. The immune system has an extraordinary potential for making T cell and B cell that recognize and neutralize any chemical entity and microbe entering the body. Certainly, some of these T cells and B cells recognize self-components; therefore, cellular mechanisms have evolved to control the activity of these self-reactive cells and achieve immunological self-tolerance. The most important in vivo biological significance of mechanisms regulating self-tolerance is to prevent the immune system from mounting an attack against the host's own tissues resulting in autoimmunity. This review summarizes recent developments in our understanding of T-helper cell tolerance and discusses how the new findings can be exploited to prevent and treat autoimmune diseases, allergy, cancer, and chronic infection, or establish donor-specific transplantation tolerance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol & Oncol, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM vboussiotis@partners.org NR 103 TC 18 Z9 19 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD NOV PY 2006 VL 84 IS 11 BP 887 EP 899 DI 10.1007/s00109-006-0098-5 PG 13 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 099JD UT WOS:000241589100002 PM 16972086 ER PT J AU Corrales, CE Pan, LY Li, HW Liberman, MC Heller, S Edge, ASB AF Corrales, C. Eduardo Pan, Luying Li, Huawei Liberman, M. Charles Heller, Stefan Edge, Albert S. B. TI Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: Growth of processes into the organ of corti SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE regeneration; stem cell; transplantation; neuron; auditory; axon ID SPIRAL GANGLION NEURONS; PARKINSONS-DISEASE; INNER-EAR; AUDITORY NEUROPATHY; HAIR-CELLS; TRANSPLANTATION; SURVIVAL; MICE; BRAIN; REPLACEMENT AB Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. To determine whether we could replace neurons lost to primary neuronal degeneration, we injected EYFP-expressing embryonic stem cell-derived mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed animals I week after destroying the cochlear nerve (spiral ganglion) cells while leaving hair cells intact by ouabain application to the round window at the base of the cochlea in gerbils. At 3 days post transplantation, small grafts were seen that expressed endogenous EYFP and could be immunolabeled for neuron-specific markers. Twelve days after transplantation, the grafts had neurons that extended processes from the nerve core toward the denervated organ of Corti. By 64-98 days, the grafts had sent out abundant processes that occupied a significant portion of the space formerly occupied by the cochlear nerve. The neurites grew in fasciculating bundles projecting through Rosenthal's canal, the former site of spiral ganglion cells, into the osseous spiral lamina and ultimately into the organ of Corti, where they contacted hair cells. Neuronal counts showed a significant increase in neuronal processes near the sensory epithelium, compared to animals that were denervated without subsequent stem cell transplantation. The regeneration of these neurons shows that neurons differentiated from stem cells have the capacity to grow to a specific target in an animal model of neuronal degeneration. (c) 2006 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Tillotson Unit Cell Biol, Boston, MA 02114 USA. Harvard & MIT, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. RP Edge, ASB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM albert_edge@meei.harvard.edu FU NIDCD NIH HHS [DC00188, DC006167, F32 DC000188, F33 DC006789, P30 DC005209, P30 DC05209, R01 DC000188, R01 DC000188-27, R01 DC006167, R01 DC007174, R01 DC007174-02] NR 38 TC 90 Z9 99 U1 0 U2 16 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD NOV PY 2006 VL 66 IS 13 BP 1489 EP 1500 DI 10.1002/neu.20310 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 103RF UT WOS:000241903700008 PM 17013931 ER PT J AU Giordano, TP Satpute, SS Striessnig, J Kosofsky, BE Rajadhyaksha, AM AF Giordano, T. P., III Satpute, S. S. Striessnig, J. Kosofsky, B. E. Rajadhyaksha, A. M. TI Up-regulation of dopamine D2L mRNA levels in the ventral tegmental area and dorsal striatum of amphetamine-sensitized C57BL/6 mice: role of Ca(v)1.3 L-type Ca2+ channels SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amphetamine; Ca(v)1.3; dorsal striatum; D2L; D2S; ventral tegmental area ID INDUCED BEHAVIORAL SENSITIZATION; MEDIUM SPINY NEURONS; NUCLEUS-ACCUMBENS; RECEPTOR ISOFORMS; LOCOMOTOR SENSITIZATION; PREFRONTAL CORTEX; CALCIUM-CHANNELS; SEEKING BEHAVIOR; COCAINE-SEEKING; D-3 RECEPTORS AB Dopamine D-2 long (D2L) and D-2 short (D2S) isoforms of the D-2 receptor play an important role in psychostimulant-induced neuronal adaptations. In this study, we used quantitative real-time PCR to specifically amplify these two splice variants to examine their mRNA expression in the dorsal striatum (dStr), nucleus accumbens (NAc) and the ventral tegmental area (VTA) of amphetamine-sensitized C57BL/6 mice. We found a significant increase in D2L mRNA in the VTA and dStr of amphetamine-treated mice that positively correlated with the sensitized locomotor response. We also found a significant increase in D2S mRNA in the VTA. We further examined the role of the Ca(v)1.3 subtype of L-type Ca2+ channels in up-regulation of D2L and D2S mRNA in the VTA. Amphetamine-pretreated Ca(v)1.3 wild-type (Ca(v)1.3(+/+)) mice exhibited sensitized behavior and a significant increase in D2L and D2S mRNA compared with saline-pretreated mice Amphetamine-pretreated homozygous Ca(v)1.3 knockout (Ca(v)1.3(-/-)) mice did not exhibit sensitized behavior. There was a significant increase in D2S mRNA, but not D2L mRNA. In conclusion, our results find that amphetamine increases D2L mRNA expression in the dStr and the VTA, an adaptation that correlates with expression of sensitized behavior and dependence on Ca(v)1.3 Ca2+ channels. C1 Cornell Univ, Weill Med Coll, Dept Pediat, Div Pediat Neurol, New York, NY 10021 USA. Univ Innsbruck, Inst Pharm, Dept Pharmacol & Toxicol, A-6020 Innsbruck, Austria. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol & Dev Neurosci,Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA USA. RP Rajadhyaksha, AM (reprint author), Cornell Univ, Weill Med Coll, Dept Pediat, Div Pediat Neurol, Room LC-625,1300 York Ave,Box 91, New York, NY 10021 USA. EM amr2011@med.cornell.edu OI Striessnig, Joerg/0000-0002-9406-7120 FU Austrian Science Fund FWF [P 17159]; NCRR NIH HHS [1S10RR022370-01]; NIDA NIH HHS [K01DA14057, K02DA00354]; NINDS NIH HHS [P30NS45776] NR 59 TC 27 Z9 28 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2006 VL 99 IS 4 BP 1197 EP 1206 DI 10.1111/j.1471-4159.2006.04186.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 098ZS UT WOS:000241562900015 PM 17026527 ER PT J AU Jacobs, JV Horak, FB Tran, VK Nutt, JG AF Jacobs, Jesse V. Horak, Fay B. Tran, Van K. Nutt, John G. TI An alternative clinical postural stability test for patients with Parkinson's disease SO JOURNAL OF NEUROLOGY LA English DT Article DE Parkinson's disease; posture; balance; UPDRS; push and release test ID CONFIDENCE ABC SCALE; BALANCE CONFIDENCE; FALLS; INSTABILITY; FEAR AB We compared the sensitivity and consistency of a new Push and Release Test versus the Pull Test (item 30 of the Unified Parkinson's Disease Rating Scale; UPDRS) as clinical measures of postural stability. Subjects with Parkinson's disease and age-matched control subjects participated in 3 protocols investigating: (1) the sensitivity and specificity of the two tests related to the subjects' balance confidence, as measured by the Activities-specific Balance Confidence (ABC) scale, (2) the inter-rater reliability of the two tests, and (3) the consistency of the perturbation forces applied to the subjects by each balance test. As a test for concurrent validity, the balance tests were also compared with the subjects' retrospective reports of fall frequency. Compared with the Pull Test, the Push and Release Test was more sensitive to subjects with low balance confidence, but less specific for subjects with high balance confidence. The inter-rater correlations were higher with the Push and Release Test. Examiners applied more consistent perturbation forces to the subjects with the Push and Release Test than with the Pull Test. The Push and Release Test correlated better with self-reported falls. Therefore, the Push and Release Test provided a more sensitive and consistent test of postural stability than the Pull Test. C1 Oregon Hlth & Sci Univ, Inst Neurol Sci, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Beaverton, OR 97006 USA. Portland VA Med Ctr, Parkinson Dis Res Educ & Clin Ctr, Beaverton, OR 97006 USA. RP Horak, FB (reprint author), Oregon Hlth & Sci Univ, Inst Neurol Sci, 505 NEW 185th Ave, Beaverton, OR 97006 USA. EM HorakF@ohsu.edu FU NIA NIH HHS [AG06457] NR 14 TC 39 Z9 39 U1 0 U2 11 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD NOV PY 2006 VL 253 IS 11 BP 1404 EP 1413 DI 10.1007/s00415-006-0224-x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 122LD UT WOS:000243227600003 PM 16788773 ER PT J AU Garcia-Alloza, M Dodwell, SA Meyer-Luehmann, M Hyman, BT Bacskai, BJ AF Garcia-Alloza, Monica Dodwell, Sarah A. Meyer-Luehmann, Melanie Hyman, Bradley T. Bacskai, Brian J. TI Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Ginkgo biloba extract (EGb 761); multiphoton microscopy neurite; oxidative stress; senile plaque; vitamin E (trolox) ID GINKGO-BILOBA EXTRACT; TRANSGENIC MICE; VITAMIN-E; MULTIPHOTON MICROSCOPY; HYDROGEN-PEROXIDE; IN-VIVO; COGNITIVE IMPAIRMENT; ALPHA-TOCOPHEROL; AMYLOID PLAQUES; MEMORY DEFICITS AB Alzheimer disease (AD) is characterized both by senile plaques and neurodegeneration, although the details of the relationship between the 2 are not well understood. We postulated that oxidative stress resulting from senile plaques may mediate plaques' effects on local neuronal processes. Using multiphoton microscopy, we directly demonstrate the generation of reactive oxygen species by senile plaques. After screening of several natural antioxidants ex vivo, we assessed in vivo the effect of 2 orally administered antioxidants in APPswe/PS1d9 transgenic mice. Both Ginkgo biloba extract and vitamin E reduced the oxidative stress resulting from senile plaques in vivo as monitored with intracranial imaging. Both treatments also lead to a progressive reversal of the structural changes in dystrophic neurites associated with senile plaques. These results suggest a causal relationship between plaque-associated oxidative stress and neuritic alterations and demonstrate for the first time that the focal neurotoxicity associated with the senile plaques of AD is partially reversible with antioxidant therapies. The quantitative ex vivo screen combined with in vivo monitoring of efficacy should lead to more effective clinical therapies for the prevention of oxidative stress and neurotoxicity in AD. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 114 16th St 2850, Charlestown, MA 02129 USA. EM bbacskai@partners.org OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIA NIH HHS [AG020570, AG024688]; NIBIB NIH HHS [EB000768] NR 47 TC 53 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2006 VL 65 IS 11 BP 1082 EP 1089 DI 10.1097/01.jnen.0000240468.12543.af PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 126MK UT WOS:000243516800007 PM 17086105 ER PT J AU Dreyer, A Delgutte, B AF Dreyer, Anna Delgutte, Bertrand TI Phase locking of auditory-nerve fibers to the envelopes of high-frequency sounds: Implications for sound localization SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID AMPLITUDE-MODULATED TONES; INTERAURAL TIME DIFFERENCES; ANTEROVENTRAL COCHLEAR NUCLEUS; MEDIAL SUPERIOR OLIVE; INFERIOR COLLICULUS; BINAURAL INTERACTION; PITCH PERCEPTION; HAIR-CELLS; GUINEA-PIG; RESPONSE PROPERTIES AB Although listeners are sensitive to interaural time differences (ITDs) in the envelope of high-frequency sounds, both ITD discrimination performance and the extent of lateralization are poorer for high-frequency sinusoidally amplitude-modulated (SAM) tones than for low-frequency pure tones. Psychophysical studies have shown that ITD discrimination at high frequencies can be improved by using novel transposed-tone stimuli, formed by modulating a high-frequency carrier by a half-wave-rectified sinusoid. Transposed tones are designed to produce the same temporal discharge patterns in high-characteristic frequency (CF) neurons as occur in low-CF neurons for pure-tone stimuli. To directly test this hypothesis, we compared responses of auditory-nerve fibers in anesthetized cats to pure tones, SAM tones, and transposed tones. Phase locking was characterized using both the synchronization index and autocorrelograms. With both measures, phase locking was better for transposed tones than for SAM tones, consistent with the rationale for using transposed tones. However, phase locking to transposed tones and that to pure tones were comparable only when all three conditions were met: stimulus levels near thresholds, low modulation frequencies (< 250 Hz), and low spontaneous discharge rates. In particular, phase locking to both SAM tones and transposed tones substantially degraded with increasing stimulus level, while remaining more stable for pure tones. These results suggest caution in assuming a close similarity between temporal patterns of peripheral activity produced by transposed tones and pure tones in both psychophysical studies and neurophysiological studies of central neurons. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. RP Dreyer, A (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [R01 DC002258, P30 DC-005209, T32 DC000038, P30 DC005209, R01 DC-002258, T32 DC-000038] NR 74 TC 41 Z9 41 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 NOV PY 2006 VL 96 IS 5 BP 2327 EP 2341 DI 10.1152/jn.00326.2006 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 095SP UT WOS:000241328900017 PM 16807349 ER PT J AU Mitra, AP Murphy, EE Ogilvy, CS AF Mitra, Alim P. Murphy, Erin E. Ogilvy, Christopher S. TI Type A intradural spinal arteriovenous fistula - Case report SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE filum terminale; arteriovenous fistula; vascular malformation.; spine ID CORD VASCULAR-LESIONS; CLASSIFICATION; MALFORMATIONS AB root In this report, the authors present the case of a patient with a unique type of spinal arteriovenous fistula. Both the location and venous angioarchitecture of this variant are uncommon, making diagnosis of the lesion challenging and raising particular management issues. The authors discuss this unusual lesion and describe its imaging features and surgical findings, as well as highlight its pathological abnormalities. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM cogilvy@partners.org NR 12 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 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD NOV PY 2006 VL 5 IS 5 BP 447 EP 450 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 100OO UT WOS:000241678600011 ER PT J AU Zhang, XP Alber, S Watkins, SC Kochanek, PM Marion, DW Graham, SH Clark, RSB AF Zhang, Xiaopeng Alber, Sean Watkins, Simon C. Kochanek, Patrick M. Marion, Donald W. Graham, Steven H. Clark, Robert S. B. TI Proteolysis consistent with activation of caspase-7 after severe traumatic brain injury in humans SO JOURNAL OF NEUROTRAUMA LA English DT Article DE apoptosis; cysteine protease; head injury; inflammation; programmed cell death ID NEURONAL APOPTOSIS; EXPRESSION; DEATH; RATS; RECRUITMENT; SUBSTRATE; PATHWAYS; ISCHEMIA; CLEAVAGE; EPILEPSY AB The expression and proteolysis of caspase family proteins are involved in the initiation and execution of apoptosis, which has been reported to occur in human and experimental traumatic brain injury (TBI). Caspase-3, -6, and -7 belong to the group of executioner caspases, which are cleaved and activated at the late, irreversible stage of apoptosis. Our previous studies demonstrated roles for caspase-1, -3, and -8 in humans after severe TBI. Here we report expression of caspase-7 mRNA and protein in humans after TBI (n = 16) and control brain-bank tissue (n = 6). Semiquantitative reverse transcription polymerase chain reaction showed no differences between caspase-7 mRNA in TBI patients versus controls (73 +/- 24 vs. 85 +/- 56 relative optical density [ROD], respectively). In contrast, Western blot analysis showed increased pro-caspase-7 in TBI patients versus controls (214 +/- 30 vs. 1 +/- 1 ROD, respectively), as well as an increase in the similar-to-20 kD proteolytic fragment in TBI patients versus controls (86 +/- 13 vs. 22 +/- 12 ROD, respectively), consistent with activation of caspase-7 after TBI in humans. Immunohistochemical analysis showed that cells expressing caspase-7 included astrocytes and neurons and possibly other glial cell types and infiltrated inflammatory cells. These data show that caspase-7 and its cleavage product are increased in human brain after TBI in many central nervous system, as well as noncentral nervous system, cell types. Thus, caspase-7 may play a role in the glial and inflammatory responses, and possibly neuronal death, after TBI in humans. C1 Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA 15260 USA. Safar Ctr Resuscitat Res, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Dept Neurol Surg, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Dept Neurol, Pittsburgh, PA USA. Univ Pittsburgh, Brain Tumor Res Ctr, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. RP Clark, RSB (reprint author), Safar Ctr Resuscitat Res, Dept Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. EM clarkrs@ccm.upmc.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [P50 NS 30318, R01 NS 38620] NR 27 TC 8 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV PY 2006 VL 23 IS 11 BP 1583 EP 1590 DI 10.1089/neu.2006.23.1583 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 106RK UT WOS:000242118200001 PM 17115905 ER PT J AU Eavey, RD Monroy, A Nicolau, Y Shabdiz, F AF Eavey, Roland D. Monroy, Angelo Nicolau, Yamileth Shabdiz, Faramarz TI Microtia repair: The case for surgical reconstruction SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID TREACHER-COLLINS-SYNDROME; CONGENITAL-MALFORMATIONS; HEMIFACIAL MICROSOMIA; AUTOGENOUS CARTILAGE; ELASTIC CARTILAGE; TRANSGENIC MOUSE; MEATAL ATRESIA; HEARING-LOSS; EAR; ANOMALIES C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Tissue Engn & Regenerat Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Seidman Lab, Boston, MA USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, 246 Charles St, Boston, MA 02114 USA. EM roland.eavey@meei.harvard.edu NR 56 TC 5 Z9 7 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2006 VL 64 IS 11 BP 1655 EP 1663 DI 10.1016/j.joms.2006.05.003 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 100SS UT WOS:000241689600013 PM 17052592 ER PT J AU Jones, D Edes, T Shreve, S Casarett, DJ AF Jones, Diane Edes, Thomas Shreve, Scott Casarett, David J. TI You won't know if you're improving unless you measure: Recommendations for evaluating hospice-veteran partnerships SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE hospice; veterans; end-of-life care; palliative care ID OF-LIFE CARE; NURSING-HOME; END; PAIN; PREFERENCES; MANAGEMENT; VALIDITY; SERVICES; CRITERIA; CANCER AB Growing evidence indicates that there are abundant opportunities to improve the care that patients receive near the end of life. Hospice care has been associated with improvements in these and other outcomes, but hospice is underused by most patient Populations. Therefore, the Department of Veterans Affairs (VA) has made hospice access a priority in its plan to improve end-of-life care for all veterans. In addition to committing funding for hospice care, the VA has also established a national network of Hospice-Veteran Partnerships (HVPs) whose goal is to improve access to hospice for veterans. This article describes the results Of a nationwide consensus project to develop measures of the success of HVPs and recommends key measures that should be used to track improvements and to identify opportunities for highly successful collaborative strategies. C1 US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. Ethos Consulting Grp, Moorestown, NJ USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Casarett, DJ (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 21 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2006 VL 32 IS 5 BP 488 EP 496 DI 10.1016/j.jpainsymman.2006.08.001 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 107XS UT WOS:000242204900016 PM 17085275 ER PT J AU Negus, SS Vanderah, TW Brandt, MR Bilsky, EJ Becerra, L Borsook, D AF Negus, S. S. Vanderah, T. W. Brandt, M. R. Bilsky, E. J. Becerra, L. Borsook, D. TI Preclinical assessment of candidate analgesic drugs: Recent advances and future challenges SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SPINAL NERVE LIGATION; NEUROPATHIC PAIN; DIABETIC-NEUROPATHY; INFLAMMATORY PAIN; RHESUS-MONKEYS; FUNCTIONAL MRI; ANIMAL-MODELS; FORMALIN TEST; RAT; MORPHINE AB In analgesic drug development, preclinical procedures are widely used to assess drug effects on pain-related behaviors. These procedures share two principal components: 1) a manipulation intended to produce a pain-like state in the experimental subject and 2) measurement of behaviors presumably indicative of that pain state. Drugs can then be evaluated for their ability to attenuate pain-related behaviors. In the simplest procedures, the pain state is produced by delivery of an acute noxious stimulus (e.g., a warm thermal stimulus), and the primary dependent measures focus on withdrawal responses or other nocifensive behaviors that increase in rate, frequency, or intensity in response to the noxious stimulus. This approach has been refined in two ways. First, new methods have been developed to induce more clinically relevant pain states. In particular, pain requiring clinical intervention is often associated with inflammation or neuropathy, and novel procedures have emerged to model these conditions and their ability to produce hypersensitive pain states, such as allodynia and hyperalgesia. Second, studies are incorporating a broader array of pain-related behaviors as dependent measures. For example, pain not only stimulates nocifensive behaviors but also suppresses many adaptive behaviors, such as feeding or locomotion. Measures of pain-suppressed behaviors can provide new insights into the behavioral consequences of pain and the effects of candidate analgesics. In addition, functional magnetic resonance imaging has emerged as a noninvasive tool for investigating changes in neural activity associated with pain and analgesia. Integration of these complementary approaches may improve the predictive validity of analgesic drug development. C1 Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr,Dept Psychiat, Belmont, MA 02478 USA. McLean Hosp, Dept Psychiat, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Atinoula A Martinos Ctr Biomed Engn, Massachusetts Gen Hosp,Dept Radiol, Belmont, MA 02178 USA. Univ Arizona, Dept Pharmacol, Tucson, AZ USA. Univ Arizona, Dept Anesthesiol, Tucson, AZ USA. Johnson & Johnson Pharmaceut Res & Dev, Dept Drug Discovery Analges, Spring House, PA USA. Univ New England, Dept Pharmacol, Coll Osteopath Med, Biddeford, ME USA. RP Negus, SS (reprint author), Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr,Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM negus@mclean.harvard.edu OI Bilsky, Edward/0000-0002-4664-5256 FU NIDA NIH HHS [R01 DA011460, R01-DA11460, R01-DA15205]; NINDS NIH HHS [R01-NS042721] NR 62 TC 120 Z9 120 U1 1 U2 11 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 NOV PY 2006 VL 319 IS 2 BP 507 EP 514 DI 10.1124/jpet.106.106377 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096UY UT WOS:000241403500001 PM 16751251 ER PT J AU Madras, BK Xie, ZH Lin, ZC Jassen, A Panas, H Lynch, L Johnson, R Livni, E Spencer, TJ Bonab, AA Miller, GM Fischman, AJ AF Madras, Bertha K. Xie, Zhihua Lin, Zhicheng Jassen, Amy Panas, Helen Lynch, Laurie Johnson, Ryan Livni, Eli Spencer, Thomas J. Bonab, Ali A. Miller, Gregory M. Fischman, Alan J. TI Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ANTINARCOLEPTIC DRUG; INDUCED WAKEFULNESS; GLUTAMATE RELEASE; MONKEY BRAIN; C-11 CFT; COCAINE; PET; AMPHETAMINE; BINDING; RAT AB 2-[(Diphenylmethyl) sulfinyl]acetamide (modafinil), prescribed principally to treat narcolepsy, is undergoing assessment for other neuropsychiatric disorders and medical conditions. The neurochemical substrates of modafinil are unresolved. We postulated that modafinil enhances wakefulness by modulating dopamine (DAT), norepinephrine (NET), or serotonin (SERT) transporter activities. In vivo, we determined DAT and NET occupancy by modafinil by positron emission tomography imaging; in vitro, we determined modafinil activity at the DAT, NET, SERT, and rhesus monkey trace amine receptor 1 (TA1). In rhesus monkey, modafinil occupancy of striatal DAT was detected by [C-11]2 beta-carbomethoxy-3 beta-4-(fluorophenyl) tropane and of thalamic NET by [C-11](S,S)-2-(alpha-(2-methoxyphenoxy)benzyl) morpholine. In vitro, modafinil effects in DAT-human embryonic kidney (HEK), NET-HEK, and SERT-HEK cells were investigated alone or combined with the TA1 receptor. Modafinil (i.v.) occupied striatal DAT sites (5 mg/kg: 35 +/- 12%, n = 4; 8 mg/kg: 54 +/- 3%, n = 3). In thalamus, modafinil occupied NET sites (5 mg/kg: 16 +/- 7.8%, n = 6; 8 mg/ kg: 44 +/- 12%; n = 2). In vitro, modafinil inhibited [H-3] dopamine (IC50 = 6.4 mu M), [H-3] norepinephrine (IC50 = 35.6 mu M), and [H-3] serotonin (IC50 > 500 mu M) transport via the human DAT, NET, and SERT. Modafinil did not activate the TA1 receptor in TA1-HEK cells, but it augmented a monoamine transporter-dependent enhancement of phenethylamine activation of TA1 in TA1-DAT and TA1-NET cells, but not in TA1-SERT cells. The present data provide compelling evidence that modafinil occupies the DAT and NET in living brain of rhesus monkeys and raise the possibility that modafinil affects wakefulness by interacting with catecholamine transporters in brain. C1 Harvard Univ, Sch Med, Dept Psychiat, New England Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, Sch Med, Dept Psychiat, New England Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM bertha_madras@hms.harvard.edu FU NCRR NIH HHS [RR00168]; NIDA NIH HHS [DA06303, DA11558, DA15305, DA16606] NR 56 TC 181 Z9 185 U1 1 U2 10 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 NOV PY 2006 VL 319 IS 2 BP 561 EP 569 DI 10.1124/jpet.106.106583 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096UY UT WOS:000241403500007 PM 16885432 ER PT J AU Madras, BK Fahey, MA Goulet, M Lin, ZC Bendor, J Goodrich, C Meltzer, PC Elmaleh, DR Livni, E Bonab, AA Fischman, AJ AF Madras, Bertha K. Fahey, Michele A. Goulet, Martin Lin, Zhicheng Bendor, Jacob Goodrich, Claudia Meltzer, Peter C. Elmaleh, David R. Livni, Eli Bonab, Ali A. Fischman, Alan J. TI Dopamine transporter (DAT) inhibitors alleviate specific Parkinsonian deficits in monkeys: Association with DAT occupancy in vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID COCAINE RECOGNITION SITES; MPTP-TREATED PRIMATES; REUPTAKE INHIBITION; DISEASE; METHYLPHENIDATE; DYSKINESIA; LEVODOPA; NOMIFENSINE; STRIATUM; BEHAVIORS AB Viable dopamine neurons in Parkinson's disease express the dopamine transporter (DAT) and release dopamine (DA). We postulated that potent DAT inhibitors, with low affinity for the serotonin transporter (SERT), may elevate endogenously released extracellular dopamine levels to provide therapeutic benefit. The therapeutic potential of eight DAT inhibitors was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated cynomolgus monkeys (Macaca fascicularis), with efficacy correlated with DAT occupancy as determined by positron emission tomography imaging in striatum. Four potent DAT inhibitors, with relatively high norepinephrine transporter, but low SERT affinities, that occupied the DAT improved activity in parkinsonian monkeys, whereas three high-affinity DAT inhibitors with low DAT occupancy did not. 2 beta-Carbomethoxy-3 alpha-(3,4-dichlorophenyl)-7 beta-hydroxy-8-methyl-8- azabicyclo[3.2.1.] octane (O-1163) occupied the DAT but had short-lived pharmacological effects. The benztropine analog difluoropine increased general activity, improved posture, reduced body freeze, and produced sleep disturbances at high doses. (1R)-2 beta-(1-Propanoyl)-3 alpha-(4-fluorophenyl) tropane (O-1369) alleviated parkinsonian signs in advanced parkinsonian monkeys, by increasing general activity, improving posture, reducing body freeze, and sedation, but not significantly reducing bradykinesia or increasing locomotor activity. In comparison with the D-2-D-3 DA receptor agonist quinelorane, O-1369 elicited oral/facial dyskinesias, whereas quinelorane did not improve posture or reduce balance and promoted stereotypy. In conclusion, DAT inhibitors with therapeutic potential combine high DAT affinity in vitro and high DAT occupancy of brain striatum in vivo with enduring daytime effects that do not extend into the nighttime. Advanced parkinsonian monkeys (80% DAT loss) respond more effectively to DAT inhibitors than mild parkinsonian monkeys (46% DAT loss). The therapeutic potential of dopamine transport inhibitors for Parkinson's disease warrants preclinical investigation. C1 Harvard Univ, Sch Med, Dept Psychiat, New England Primate Res Ctr,Div Neurochem, Southborough, MA 01772 USA. Organix Inc, Woburn, MA USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, Sch Med, Dept Psychiat, New England Primate Res Ctr,Div Neurochem, 1 Pine Hill, Southborough, MA 01772 USA. EM bertha_madras@hms.harvard.edu OI Bendor, Jacob/0000-0003-1455-4891 FU NCRR NIH HHS [RR00168]; NIDA NIH HHS [DA06303, DA11558]; NIMH NIH HHS [N01 MH80005]; NINDS NIH HHS [NS30556] NR 40 TC 14 Z9 14 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2006 VL 319 IS 2 BP 570 EP 585 DI 10.1124/jpet.106.105312 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096UY UT WOS:000241403500008 PM 16885433 ER PT J AU Valdiserri, RO AF Valdiserri, Ronald O. TI The continued spread of HIV in the United States: Prevention failure or systems defect? SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Editorial Material ID HEALTH; PROGRAMS; FUTURE; TIME; CARE C1 Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. RP Valdiserri, RO (reprint author), US Dept Vet Affairs, Publ Hlth Strateg Hlth Care Grp, 810 Vermont Ave NW, Washington, DC 20420 USA. EM R.Valdiserri@va.gov NR 35 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD NOV-DEC PY 2006 VL 12 IS 6 BP 586 EP 589 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 099KN UT WOS:000241593400013 PM 17041308 ER PT J AU Hubbard, SL Fitzgerald, SG Reker, DM Boninger, ML Cooper, RA Kazis, LE AF Hubbard, Sandra L. Fitzgerald, Shirley G. Reker, Dean M. Boninger, Michael L. Cooper, Rory A. Kazis, Lewis E. TI Demographic characteristics of veterans who received wheelchairs and scooters from Veterans Health Administration SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE age; assistive technology; equity; ethnicity; power wheelchair; race; rehabilitation; sex; standard manual wheelchair; wheeled mobility equipment ID SPINAL-CORD-INJURY; PUSHRIM BIOMECHANICS; ANSI/RESNA STANDARDS; JOINT KINETICS; PROPULSION; SHOULDER; PERFORMANCE; DISABILITY; MOBILITY; FORCES AB Little is known about the reasoning process clinicians use when prescribing wheeled mobility equipment (WAM) or about the outcomes of this process, i.e., how many devices are prescribed, to whom, how often, and at what cost. This study characterized veterans who received WME from the Veterans Health Administration. We analyzed variance in wheelchair provision based on sex, race/ethnicity, diagnosis, and age. Three years of data from the National Prosthetics Patient Database and the National Patient Care Database were merged, yielding more than 77,000 observations per fiscal year. Logistic regression analysis revealed associations between WME provision and age, sex, and race/ethnicity, when analysis was controlled for diagnosis and number of comorbidities. Hispanics (odds ratio [OR] = 1.864), African Americans (OR = 1.360), and American Indians/Asians (OR = 1.585) were more likely than Caucasians to receive standard wheelchairs. Hispanics (OR = 0.4), African Americans (OR = 0.7), and American Indians/Asians (OR = 0.4) were less likely than Caucasians to receive scooters. C1 N Florida S Georgia Vet Hlth Syst, Dept Vet Affairs, Rehabil Outcomes Res Ctr Excellence, Gainesville, FL USA. Univ Florida, Dept Occupat Therapy, Gainesville, FL USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Kansas City VA Med Ctr, Kansas City, MO USA. Univ Kansas, Med Ctr, Dept Hlth Policy & Management, Kansas City, MO USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. VA Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 151R-1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM sgf9@pitt.edu OI Kazis, Lewis/0000-0003-1800-5849; Boninger, Michael/0000-0001-6966-919X NR 47 TC 21 Z9 22 U1 1 U2 5 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 NOV-DEC PY 2006 VL 43 IS 7 BP 831 EP 844 DI 10.1682/JRRD.2005.11.0174 PG 14 WC Rehabilitation SC Rehabilitation GA 156FO UT WOS:000245633700006 PM 17436170 ER PT J AU Segal, AD Orendurff, MS Mute, GK McDowell, ML Pecoraro, JA Shofer, J Czerniecki, JM AF Segal, Ava D. Orendurff, Michael S. Mute, Glenn K. McDowell, Martin L. Pecoraro, Janice A. Shofer, Jane Czerniecki, Joseph M. TI Kinematic and kinetic comparisons of transfemoral amputee gait using C-Leg (R) and Mauch SNS (R) prosthetic knees SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputee; biomechanics; C-Leg (R); gait; kinematics; kinetics; knee; microprocessor; rehabilitation; transfernoral ID PHASE-CONTROL; COMPONENTS; JOINT; REHABILITATION; OSTEOARTHRITIS; DEGENERATION; BIOMECHANICS; AMBULATION; DENSITY; SPEED AB The C-Leg (R) (Otto Bock, Duderstadt, Germany) is a microprocessor-controlled prosthetic knee that may enhance amputee gait. This intrasubject randomized study compared the gait biomechanics of transfemoral amputees wearing the C-Lege with those wearing a common noncomputerized prosthesis, the Mauch SNS (R) (Ossur, Reykjavik, Iceland). After subjects had a 3-month acclimation period with each prosthetic knee, typical gait biomechanical data were collected in a gait laboratory. At a controlled walking speed (CWS), peak swing phase knee-flexion angle decreased for the C-Lege group compared with the Mauch SNS (R) group (55.2 degrees +/- 6.5 degrees vs 64.41 degrees +/- 5.8 degrees, respectively; p = 0.005); the C-Leg (R) group was similar to control subjects' peak swing knee-flexion angle (56.0 degrees +/- 3.4 degrees). Stance knee-flexion moment increased for the C-Legs group compared with the Mauch SNS (R) group (0.142 +/- 0.05 vs 0.067 +/- 0.07 N(.)m, respectively; p = 0.01), but remained significantly reduced compared with control subjects (0.477 +/- 0.1 N(.)m). Prosthetic limb step length at CWS was less for the C-Leg (R) group compared with the Mauch SNS (R) group (0.66 +/- 0.04 vs 0.70 +/- 0.06 in, respectively; p = 0.005), which resulted in increased symmetry between limbs for the C-Leg (R) group. Subjects also walked faster with the C-Leg (R) versus the Mauch SNS (R) (1.30 +/- 0.1 vs 1.21 +/- 0.1 m/s, respectively; p = 0.004). The C-Lee prosthetic limb vertical ground reaction force decreased compared with the Mauch SNS (R) (96.3 +/- 4.7 vs 100.3 +/- 7.5 % body weight, respectively; p = 0.0092). C1 VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Dept Vet Affairs Rehabil Res & Dev, Seattle, WA 98108 USA. Univ Washington, Dept Engn Mech, Seattle, WA 98195 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. RP Segal, AD (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Dept Vet Affairs Rehabil Res & Dev, 1660 S Columbian Way,Mail Stop 151, Seattle, WA 98108 USA. EM avasegal@gmail.com NR 30 TC 85 Z9 89 U1 6 U2 26 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 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD NOV-DEC PY 2006 VL 43 IS 7 BP 857 EP 869 DI 10.1682/JRRD.2005.09.0147 PG 13 WC Rehabilitation SC Rehabilitation GA 156FO UT WOS:000245633700008 PM 17436172 ER PT J AU Growdon, WB Wolfberg, AJ Feltmate, CM Goldstein, DP Genest, DR Chinchilla, ME Berkowitz, RS Lieberman, ES AF Growdon, Whitfield B. Wolfberg, Adam J. Feltmate, Colleen M. Goldstein, Donald P. Genest, David R. Chinchilla, Manuel E. Berkowitz, Ross S. Lieberman, Ellice S. TI Postevacuation hCG levels and risk of gestational trophoblastic neoplasia among women with partial molar pregnancies SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 13th World Congress on Gestational Trophoblastic Disease CY OCT 23-26, 2005 CL Hong Kong, PEOPLES R CHINA DE gestational trophoblastic neoplasms; human chorionic gonadotropin; molar pregnancy ID PARTIAL HYDATIDIFORM MOLES; DISEASE; DIAGNOSIS; PROGRESS; TUMORS AB OBJECTIVE: To develop human chorionic gonadotropin (hCG) criteria that determine a patient's risk of developing persistent gestational trophoblastic neoplasia (GTN) or achieving remission after partial mole evacuation. STUDY DESIGN: We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 284 women with partial molar pregnancies diagnosed between 1973 and 2003. RESULTS: An hCG level > 199 mIU/mL in the third through eighth week following molar evacuation was associated with at least a 35% risk of GTN. CONCLUSION: Women with partial mole who have elevated hCG levels within the first few weeks after molar evacuation are at increased risk for developing GTN. C1 Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 16 TC 6 Z9 6 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD NOV PY 2006 VL 51 IS 11 BP 871 EP 874 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 108EI UT WOS:000242222700005 PM 17165432 ER PT J AU Feltmate, CM Growdon, WB Wolfberg, AJ Goldstein, DP Genest, DR Chinchilla, ME Lieberman, ES Berkowitz, RS AF Feltmate, Colleen M. Growdon, Whitfield B. Wolfberg, Adam J. Goldstein, Donald P. Genest, David R. Chinchilla, Manuel E. Lieberman, Ellice S. Berkowitz, Ross S. TI Clinical characteristics of persistent gestational trophoblastic neoplasia after partial hydatidiform molar pregnancy SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 13th World Congress on Gestational Trophoblastic Disease CY OCT 23-26, 2005 CL Hong Kong, PEOPLES R CHINA DE gestational trophoblastic neoplasms; trophoblastic cancer; molar pregnancy; human chorionic gonadotropins ID PARTIAL MOLES; DISEASE; EXPERIENCE; DIAGNOSIS; TUMOR AB OBJECTIVE: To identify clinical characteristics associated with developing persistent gestational trophoblastic neoplasia (GTN) after partial hydatidiform molar pregnancy (PHM). STUDY DESIGN: Utilizing the Donald P. Goldstein database at the New England Trophoblastic Disease Center, 284 women with partial molar pregnancy diagnosed between 1973 and 2003 were identified. Clinical characteristics, such as gravidity, parity, age, uterine size, gestational age at diagnosis, human chorionic gonadotropin levels at presentation and time to development of persistence (GTN) were analyzed. Data were also divided into 2 cohorts, an earlier one (1973-1989) and a later one (1990-2003), in order to look at potential changes over time. RESULTS: GTN developed in 5.6% of partial molar pregnancies. Older maternal age was significantly associated with development of persistent GTN in the earlier cohort but not in the recent cohort. Previous molar pregnancy was also statistically significantly more common in patients who developed persistence between 1973 and 1989. CONCLUSION: Older age at diagnosis and history of prior mole were significantly more common in women who developed persistence after partial molar pregnancy in the earlier cohort but not in the recent cohort. In recent years no clinical factor was significantly associated with the development of GTN after PHM. C1 Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Clin & Epidemiol Res, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Feltmate, CM (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA. EM cfeltmate@partners.org NR 19 TC 33 Z9 37 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD NOV PY 2006 VL 51 IS 11 BP 902 EP 906 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 108EI UT WOS:000242222700011 PM 17165438 ER PT J AU Feist, E Burmester, GR AF Feist, Eugen Burmester, Gerd R. TI Citrullinated antigens: Just diagnostic tools or pathogenic targets in rheumatoid arthritis? SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID PEPTIDYLARGININE DEIMINASE-4; PADI4 GENE; AUTOANTIBODIES; FIBRINOGEN; DEIMINATION; ANTIBODIES; AUTOANTIGEN; POPULATION; PROTEINS; TISSUE C1 Charite Univ Med Berlin, Free Univ Berlin, Dept Rheumatol & Clin Immunol, D-10098 Berlin, Germany. Humboldt Univ, D-1086 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Lab, Boston, MA 02115 USA. RP Burmester, GR (reprint author), Charite Univ Med Berlin, Free Univ Berlin, Dept Rheumatol & Clin Immunol, D-10098 Berlin, Germany. EM gerd.burmester@charite.de NR 22 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 33 IS 11 BP 2103 EP 2104 PG 2 WC Rheumatology SC Rheumatology GA 105DX UT WOS:000242010700001 PM 17086596 ER PT J AU Latini, DM Penson, DF Wallace, KL Lubeck, DP Lue, TF AF Latini, David M. Penson, David F. Wallace, Katrine L. Lubeck, Deborah P. Lue, Tom F. TI Clinical and psychosocial characteristics of men with erectile dysfunction: Baseline data from ExCEED (TM) SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE erectile dysfunction; psychosocial characteristics ID QUALITY-OF-LIFE; SELF-ESTEEM; RELATIONSHIP QUESTIONNAIRE; INTERNATIONAL INDEX; DEPRESSIVE SYMPTOMS; VALIDATION; SILDENAFIL; IMPOTENCE; IMPACT AB Introduction. Erectile dysfunction (ED) is associated with psychological impairment, and further research is required to understand their relationship. Aim. We present descriptive baseline results from a longitudinal observational study of North American men seeking treatment for ED. Methods. Patients completed clinical and health-related quality-of-life information at baseline and three follow-up points over 12 months; 162 patients had usable baseline data, including clinical history and current status, sociodemographic information, and standard paper-and-pencil scales of psychosocial characteristics. Scores on the International Index of Erectile Functioning erectile functioning subscale were collapsed into mild (N = 27), moderate (N = 41), or severe (N = 94) categories. Using chi-square, ANOVA, and logistic regression, we identified baseline characteristics associated with ED severity. Main Outcome Measure. The main outcome measure was the degree of psychosocial impairment associated with mild, moderate, and severe ED. Results. Severe ED was significantly associated with not having a regular sex partner; a history of prostate cancer; and worse scores on measures of positive affect, belonging/loneliness, sexual self-efficacy-strength, psychological adjustment, marital happiness, anxiety at last intercourse, and depression. In a multivariate logistic regression model, poorer sexual self-efficacy was most closely associated with severe ED. The model rescaled R-2 was 0.63 (area-under-the-curve, 0.91). Conclusions. Severe ED is related to impairment across a broad range of psychosocial domains, and clinicians should consider offering patients assistance in dealing with its psychosocial impact. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utlizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Univ So Calif, Keck Sch Med, Dept Urol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Latini, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utlizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM latini@bcm.tmc.edu OI Latini, David/0000-0002-6161-4861 NR 29 TC 44 Z9 45 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD NOV PY 2006 VL 3 IS 6 BP 1059 EP 1067 DI 10.1111/j.1743-6109.2006.00331.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 098ZL UT WOS:000241562200016 PM 17100939 ER PT J AU Latini, DM Penson, DF Wallace, KL Lubeck, DP Lue, TF AF Latini, David M. Penson, David F. Wallace, Katrine L. Lubeck, Deborah P. Lue, Tom F. TI Longitudinal differences in psychological outcomes for men with erectile dysfunction: Results from ExCEED (TM) SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE erectile dysfunction; health-related quality of life; psychosocial characteristics; longitudinal analysis ID QUALITY-OF-LIFE; INTERPERSONAL RELATIONSHIP SCALES; DEPRESSIVE SYMPTOMS; SELF-ESTEEM; SILDENAFIL/; VALIDATION; DISEASE AB Introduction. The direction of the relationship between psychological adjustment and erectile dysfunction (ED) is unclear and may differ for different men, and few studies have examined psychological outcomes for men receiving ED treatment. Aim. This study assessed the impact of ED therapy at baseline and 12-month follow-up, using standard psychological measures. Methods. Using an observational ED registry, we collected clinical and psychosocial data at baseline and 3, 6, and 12 months. Participants had (i) a patient-reported outcomes questionnaire at baseline and at least one follow-up; and (ii) data about ED treatments received during the study. Treated men were classified as responders based on improvements in International Index of Erectile Function scores from baseline to 12 months. Main Outcome Measures. The main outcome measures were changes in psychological outcomes in relation to treatment status and baseline ED severity. Results. Of 153 patients, 40 responded to treatment, 49 did not respond to treatment, and 64 did not receive treatment. Treatment responders reported significant improvements in 12-month sexual self-efficacy but only small improvements or no change across five other psychological domains, whereas nonresponders reported small decrements. There was a trend for differences in sexual self-efficacy to vary by baseline ED severity, as well as by treatment response. Conclusions. Diagnosing and successfully treating ED significantly affects patient psychological adjustment, so providers should actively diagnose and treat ED. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Univ So Calif, Keck Sch Med, Dept Urol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Latini, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM latini@bcm.tmc.edu OI Latini, David/0000-0002-6161-4861 NR 26 TC 17 Z9 17 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD NOV PY 2006 VL 3 IS 6 BP 1068 EP 1076 DI 10.1111/j.1743-6109.2006.00332.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 098ZL UT WOS:000241562200017 PM 17100940 ER PT J AU Murachovsky, J Ikemoto, RY Nascimento, LGP Fujiki, EN Milani, C Warner, JJP AF Murachovsky, Joel Ikemoto, Roberto Y. Nascimento, Luis G. P. Fujiki, Edison N. Milani, Carlo Warner, Jon J. P. TI Pectoralis major tendon reference (PMT): A new method for accurate restoration of humeral length with hemiarthroplasty for fracture SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID PROXIMAL HUMERUS; RETROSPECTIVE EVALUATION; SHOULDER ARTHROPLASTY; 4-PART FRACTURES; REPLACEMENT; TUBEROSITY; OUTCOMES; REASONS; GROOVE AB For hemiarthroplasty reconstruction of a proximal humeral fracture, accurate restoration of humeral head position is challenging, and incorrect prosthetic placement is associated with a poor outcome of surgical treatment. The purpose of this study was to validate the pectoralis major tendon as a reproducible landmark for accurate restoration of humeral length with hemiarthroplasty reconstruction. We dissected 20 cadavers (40 shoulders), and the distance between the upper border of the pectoralis major tendon insertion on the humerus and the top of the humeral head was measured (PMT). The PMT averaged 5.6 +/- 0.5 cm (with a confidence level of 95%). In only 4 of 40 shoulders did this distance exceed 6.0 cm, and there was no correlation between the size of the patient and this measurement. The PMT is a useful landmark that will aid in accurate restoration of humeral length when reconstructing complex proximal humeral fractures where landmarks are otherwise lost because of fracture comminution. C1 Fac Med ABC, Dept Orthopaed Surg, Santo Andre, Brazil. Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Shoulder Serv, Boston, MA 02115 USA. RP Murachovsky, J (reprint author), 1269 Pacaembu, BR-01235000 Sao Paulo, Brazil. EM jd.mura@uol.com.br NR 36 TC 40 Z9 49 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD NOV-DEC PY 2006 VL 15 IS 6 BP 675 EP 678 DI 10.1016/j.jse.2005.12.01 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 117IY UT WOS:000242867900005 PM 17055748 ER PT J AU Goldman, B Sheppard, L Kujawa, SG Seixas, NS AF Goldman, Bryan Sheppard, Lianne Kujawa, Sharon G. Seixas, Noah S. TI Modeling distortion product otoacoustic emission input/output functions using segmented regression SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HEARING-IMPAIRED EARS; PURE-TONE THRESHOLDS; LINEAR-REGRESSION; DPOAE GENERATION; CLINICAL UTILITY; LIKELIHOOD RATIO; CHANGE-POINTS; DELTA-METHOD; MECHANISMS; OTOTOXICITY AB Distortion product otoacoustic emissions (DPOAEs) are low-level acoustic signals, the detection of which involves extraction from a background of noise. Boege and Janssen [J. Acoust. Soc. Am. 111, 1810-1818 (2002)] described a method for modeling the presence and growth of these responses. While improving growth function parameter estimation, this technique excludes a significant fraction of the data (especially low-level responses), and relies on ad hoc model fit acceptance criteria. The statistical difficulties associated with these limitations are described, and a weighted segmented linear regression model that avoids them is proposed. A simple test is presented for the presence of DPOAE growth. This technique is compared to that of Boege and Janssen in a dataset of 9 556 input/output (I/O) functions collected over 4 years on 866 ears from 379 construction apprentices and 63 age-matched controls. Comparisons are made on the entire dataset and within audiometric hearing loss categories. Segmented regression avoids the statistical pitfalls of the previous method, allows estimation of the threshold and slope of auditory response on a far greater number of I/O functions, and improves estimation of these parameters in this dataset. The Potential for this method to yield more sensitive metrics of hearing function and compromise is discussed. (c) 2006 Acoustical Society of America. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Goldman, B (reprint author), Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. FU NIOSH CDC HHS [5 R01 OH03912] NR 64 TC 12 Z9 12 U1 1 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 2006 VL 120 IS 5 BP 2764 EP 2776 DI 10.1121/1.2258871 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 104CO UT WOS:000241933800033 PM 17139737 ER PT J AU Stewart, SE Illmann, C Geller, DA Leckman, JF King, R Pauls, DL AF Stewart, S. Evelyn Illmann, Cornelia Geller, Daniel A. Leckman, James F. King, Robert Pauls, David L. TI A controlled family study of attention-deficit/hyperactivity disorder and Tourette's disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; Tourette's disorder; familial; genetic; obsessive-compulsive disorder ID DEFICIT HYPERACTIVITY DISORDER; COMPLEX SEGREGATION ANALYSIS; OBSESSIVE COMPULSIVE SCALE; TIC SEVERITY; CHILDREN; ADHD; COMORBIDITY; VALIDITY; SUBTYPES; TRANSMISSION AB Objective: Although attention-deficit/hyperactivity disorder (ADHD) is frequently comorbid with Tourette's disorder (TD), it is unclear whether they have a common genetic etiology. Familial relationships between DSM-IV ADHD and TD are studied in TD + ADHD, TD-only (TD-ADHID), ADHD-only (ADHD-TD), and control groups. Method: Case-control, direct-interview family study of 692 relatives of 75 TD + ADHD, 74 TD-only, 41 ADHD-only, and 49 control probands collected between 1999 and 2004. Age-corrected prevalence rates, odds ratios, and predictors of TD, ADHD, and OCD among relatives are estimated from blinded best-estimate diagnoses using survival Kaplan-Meier and generalized estimating equation regression analyses. Results: In relatives of the TD-only group, although ADHD exceeded control rates (p = .03), ADHD-TD (p = .51) rates were not increased. In the ADHD-only group, TD was increased (p = .004) but TD-ADHD rates were not increased (p = .18). Comorbid ADHD + TD diagnoses in relatives were elevated in all case groups (p <= .03). TD in relatives predicted comorbid ADHD (p < .001), and ADHD in relatives predicted comorbid TD (p < .001). OCD in relatives predicted both ADHD (p = .002) and TD (p < .001) in relatives. Conclusions: TD and ADHD are not alternate phenotypes of a single underlying genetic cause. There is an increased risk of comorbid ADHD and TD in affected families, possibly reflecting some overlapping neurobiology or pathophysiology. C1 Massachusetts Gen Hosp, PNGU, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. RP Pauls, DL (reprint author), Massachusetts Gen Hosp, PNGU, 185 Cambridge St, Boston, MA 02114 USA. EM dpauls@ngu.mgb.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH NIH HHS [MH-49351]; NINDS NIH HHS [NS-16648] NR 48 TC 42 Z9 45 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2006 VL 45 IS 11 BP 1354 EP 1362 DI 10.1097/01.chi.0000235075.25038.5a PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600010 PM 17075358 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 III SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Louisiana State Univ, Sch Med, Div Infant Child & Adolescent Psychiat, Dept Psychiat, New Orleans, LA 70018 USA. Univ Louisville, Div Child Adolescent & Family Psychiat, Hlth Sci Ctr, Louisville, KY 40292 USA. Zucker Hillside Hosp, Div Child & Adolescent Psychiat, Long Isl Jewish Med Ctr, Glen Oaks, NY USA. Univ Colorado, Ctr Hlth Sci, Denver, CO 80202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Drell, MJ (reprint author), Louisiana State Univ, Sch Med, New Orleans Adolescent Hosp & Community Syst Care, 210 State St, New Orleans, LA 70018 USA. EM mdrell@lsuhsc.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2006 VL 45 IS 11 BP 1370 EP 1380 DI 10.1097/01.chi.0000230163.52331.9f PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 096ZM UT WOS:000241415600012 PM 17075360 ER PT J AU Velmahos, GC Spaniolas, K Alam, HB de Moya, M Gervasini, A Petrovick, L Conn, AK AF Velmahos, George C. Spaniolas, Konstantinos Alam, Hasan B. de Moya, Marc Gervasini, Alice Petrovick, Laurie Conn, Alasdair K. TI Falls from height: Spine, spine, spine! SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CERVICAL-SPINE; BLUNT TRAUMA; INJURIES; FRACTURES; PATTERNS; VICTIMS AB BACKGROUND: Falls from a height are a major cause of morbidity and hospital cost. Spinal injury is frequently associated with falls from height, but reliable predictive factors have not been identified. Diagnostic evaluation of the spine is complex and debated. Our objective was to characterize spinal injury after falls from height and identify predictive factors of spinal injuries. STUDY DESIGN: Medical records of patients with falls from height > 10 feet admitted in a Level I trauma center during a period of 66 months were reviewed. Univariate and multivariate analyses were performed to identify independent risk factors of spinal injuries. RESULTS: Of 414 patients, 127 (31%) suffered 277 spinal injuries. Multiple spinal injuries at different levels were found in 62 (49%) patients; in 19 (15%) spinal injuries were at noncontinuous levels. The only independent predictor of spinal injury was alcohol intoxication (odds ratio 3.305; 95% CI, 1.75-6.242; p < 0.001) but the number of intoxicated patients was low and the predictive ability weak. Level of falls from height did not correlate with likelihood of spinal injury. Twenty-four of 107 (22%) patients with spinal injuries and a reliable clinical examination had no symptoms related to the spine; all but 2 had distracting injuries. CONCLUSIONS: Spinal injury is frequent among survivors of falls from height > 10 feet. Because of the absence of reliable predictors of spinal injury, the possibility of multiple noncontinuous fractures, and the presence of distracting injuries clouding the clinical presentation, aggressive evaluation of the entire spine is warranted. C1 Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 21 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD NOV PY 2006 VL 203 IS 5 BP 605 EP 611 DI 10.1016/j.jamcollsurg.2006.07.002 PG 7 WC Surgery SC Surgery GA 102XB UT WOS:000241845600003 PM 17084320 ER PT J AU Hutter, MM Rowell, KS Devaney, LA Sokal, SM Warshaw, AL Abbott, WM Hodin, RA AF Hutter, Matthew M. Rowell, Katherine S. Devaney, Lynn A. Sokal, Suzanne M. Warshaw, Andrew L. Abbott, William M. Hodin, Richard A. TI Identification of surgical complications and deaths: An assessment of the traditional surgical morbidity and mortality conference compared with American College of Surgeons-National Quality Improvement Program SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 91st Annual Clinical Congress of the American-College-of-Surgeons CY OCT 16-20, 2005 CL San Francisco, CA SP Amer Coll Surg ID VETERANS-AFFAIRS; MEDICAL ERRORS; CARE AB BACKGROUND: Despite advances by surgeons in assessing quality and safety, the traditional surgical morbidity and mortality (M&M) conference has mostly remained unchallenged and unchanged. The goal of this study was to compare data as reported in a traditional M&M conference to data collected using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) techniques. STUDY DESIGN: A retrospective study was performed comparing data from the M&M conference in a general surgery division, in which complications and deaths were identified by residents or attendings, to data compiled by a nationally audited nurse reviewer from the ACS-NSQIP from July 1, 2002, to June 30, 2003. RESULTS: Mortality rates calculated by traditional M&M conference (53 deaths in 5,905 patients), compared with the ACS-NSQIP nurse reviewer (28 deaths in 1,439 patients; 24% sample), were 0.9% versus 1.9%, respectively (p = 0.001). Complication rates reported in M&M were 6.4% versus 28.9% ACS-NSQIP (p < 0.0001). Subgroup analyses showed that mortality rates, as reported in conference, were substantially lower for both in-hospital and postdischarge patients, when compared with ACS-NSQIP. All subclassifications of complications, as presented in conference, were also lower, compared with ACS-NSQIP. CONCLUSIONS: Traditional surgical M&M reporting considerably underreports both in-hospital and postdischarge complications and deaths as compared with ACS-NSQIP. Approximately one of two deaths and three of four complications were not reported in the M&M conference at our institution. A Web-based reporting system based on an ACS-NSQIP platform was created to automate, facilitate, and standardize data on surgical morbidity and mortality. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang ACC 335, Boston, MA 02114 USA. EM mhutter@partners.org NR 17 TC 92 Z9 92 U1 1 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 NOV PY 2006 VL 203 IS 5 BP 618 EP 624 DI 10.1016/j.jamcollsurg.2006.07.010 PG 7 WC Surgery SC Surgery GA 102XB UT WOS:000241845600005 PM 17084322 ER PT J AU Friedlander, AH Vagiela, JA Paterno, VI Mahler, ME AF Friedlander, Arthur H. Vagiela, John A. Paterno, Victoria I. Mahler, Michael E. TI The neuropathology, medical management and dental implications of autism SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Review DE autism; neurodevelopmental disorders; Asperger's syndrome; pervasive developmental disorder; adverse effects; dental treatment ID ADVERSE DRUG-INTERACTIONS; DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; SLEEP PROBLEMS; CHILDREN; FAMILIES; DIAGNOSIS; PREVALENCE; SYMPTOMS; PATTERNS AB Background. A paucity of information exists in the dental literature about autism and its dental implications. Types of Studies Reviewed. The authors conducted a MEDLINE search for the period 2000 through 2006, using the term "autism," with the aim of defining the condition's clinical manifestations, dental and medical treatment and dental implications. Results. Autism is a severe developmental. brain disorder that appears in infancy, persists throughout life, and is characterized by impaired social interaction, abnormalities in communication (both verbal and nonverbal and restricted interests. Often accompanying the disorder are behavioral disturbances-such as self-mutilation, aggression, psychiatric symptoms and seizures-that necessitate the administration of multiple medications to help the affected person participate effectively in the educational and rehabilitative process. Clinical Implications. Dentists caring for people with autism must be familiar with the manifestations of the, disease and its associated features so that they can garner the maximum level of patient cooperation. They also must be familiar with the medications used to treat the associated features of the disorder because many of them cause untoward orofacial and systemic reactions and may precipitate adverse interactions with dental therapeutic agents. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 102 TC 36 Z9 37 U1 3 U2 9 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 NOV PY 2006 VL 137 IS 11 BP 1517 EP 1527 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 108MY UT WOS:000242245100020 PM 17082277 ER PT J AU Moore, PA Boynes, SG Hersh, EV DeRossi, SS Sollecito, TP Goodson, JM Leonel, JS Floros, C Peterson, C Hutcheson, M AF Moore, Paul A. Boynes, Sean G. Hersh, Elliot V. DeRossi, Scott S. Sollecito, Thomas P. Goodson, J. Max Leonel, Juliana S. Floros, Constantinos Peterson, Carrie Hutcheson, Matthew TI Advances in dental products: The anesthetic efficacy of 4 percent articaine 1 : 200,000 epinephrine: Two controlled clinical trials SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE articaine; epinephrine; dentistry; local anesthesia; clinical trial ID CONTRAINDICATIONS; VASOCONSTRICTORS; DENTISTRY; LIDOCAINE AB Objectives. The authors conducted two double-blinded, randomized, multicenter clinical trials to determine the efficacy and clinical anesthetic characteristics of 4 percent articaine hydrochloride (HCl) with 1:200,000 epinephrine (A200) as compared with those of 4 percent articaine HCl with 1:100,000 epinephrine (A100) and 4 percent articaine HCl with epinephrine (Aw/o). Methods. During separate testing sessions, members of the authors' research team used three articaine study formulations to induce either inferior alveolar nerve block anesthesia (Trial 1) or maxillary infiltration anesthesia (Trial 2). In each trial subjects received, in a randomized sequence, each of the three formulations to determine efficacy (success rate) and anesthetic characteristics (onsets time and duration). The authors evaluated pupal anesthesia via subjects' response to electric pulp testing (EPT). Results. A total of 126 subiects were enrolled in the two studies (63 subjects in each trial). In both mandibular maxillary trials, the success rates for inducing profound,ahesthesia (EPT, score >= 80), the mean onset times and the mean durations of anesthesia were similar for both epinephrine-containing formulations (A200 and A100). In subjects who received the formulation containing no epinephrine (Aw/o), the success rate for profound anesthesia was significantly less. Conclusion. These studies demonstrated that inclusion of epinephrine in 4 percent articaine anesthetic formulations is essential for achieving profound anesthesia. The authors found that the A200 provided a level of pupal anesthesia comparable with that of the A100 formulation. C1 Univ Pittsburgh, Sch Dent Med, Oral Hlth Sci Inst, Dept Anesthesiol, Pittsburgh, PA 15261 USA. Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. Forsyth Inst, Dept Pharmacol, Boston, MA USA. Novocol Pharmaceut Cancada, Cambridge, ON, Canada. Tegra Analyt, Doylestown, PA USA. RP Moore, PA (reprint author), Univ Pittsburgh, Sch Dent Med, Oral Hlth Sci Inst, Dept Anesthesiol, 552 Salk Hall, Pittsburgh, PA 15261 USA. EM pam7@pitt.edu NR 19 TC 34 Z9 34 U1 0 U2 2 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 NOV PY 2006 VL 137 IS 11 BP 1572 EP 1581 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 108MY UT WOS:000242245100027 PM 17082284 ER PT J AU Williams, BA Lindquist, K Moody-Ayers, SY Walter, LC Covinsky, KE AF Williams, Brie A. Lindquist, Karla Moody-Ayers, Sandra Y. Walter, Louise C. Covinsky, Kenneth E. TI Functional impairment, race, and family expectations of death SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE functional impairment; palliative care; geriatric ID OF-LIFE CARE; SERIOUSLY ILL PATIENTS; NURSING-HOME RESIDENTS; ADVANCE DIRECTIVES; END; OLDER; PREFERENCES; COMMUNICATION; ETHNICITY; CANCER AB To assess the effect of functional impairment on family expectations of death and to examine how this association varies by race. Cross-sectional. Community based. Two thousand two hundred thirty-seven family members of decedents from the Health and Retirement Survey (HRS), a national study of persons aged 50 and older. Families were interviewed within 2 years of the HRS participant's death. The primary outcome was whether death was expected. The primary predictors were the decedent's functional status (impairment in any activity of daily living (ADL; eating, dressing, transferring, toileting, or bathing) during the last 3 months of life and the decedent's race. Overall, 58% of families reported that their family member's death was expected. Expecting death was strongly associated with functional impairment; 71% of families of decedents with ADL disability expected death, compared with 24% of those without ADL disability (P <.01). Death was expected more often in families of white decedents (60%) than African Americans (49%) (P <.01), although the effect of ADL disability was similar in both groups. After adjustment for potentially confounding factors, there were still significant associations between expecting death and functional impairment (odds ratio (OR) = 3.58, 95% confidence interval (CI) 2.73-4.70), and families of African Americans expected death less often than families of white decedents (OR = 0.63, 95% CI = 0.46-0.86). Family members of older adults expected death only 58% of the time. Families of functionally impaired older people were more likely to expect death when it occurred than were families of older people who were not functionally impaired, and the expectation of death was lower for families of African Americans than for whites. C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Williams, BA (reprint author), 4150 Clement St Box 181-G, San Francisco, CA 94121 USA. EM brie.williams@ucsf.edu FU NIA NIH HHS [T32-AG00212, 5 R01 AG023626-02] NR 43 TC 6 Z9 6 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2006 VL 54 IS 11 BP 1682 EP 1687 DI 10.1111/j.1532-5415.2006.00941.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 100NS UT WOS:000241676400008 PM 17087694 ER PT J AU Vig, EK Taylor, JS Starks, H Hopley, EK Fryer-Edwards, K AF Vig, Elizabeth K. Taylor, Janelle S. Starks, Helene Hopley, Elizabeth K. Fryer-Edwards, Kelly TI Beyond substituted judgment: How surrogates navigate end-of-life decision-making SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Bioethics-and-Humanities CY OCT 28-31, 2004 CL Philadelphia, PA SP Amer Soc Bioethics & Humanities DE surrogate decision-making; advance care planning; substituted judgment; qualitative research ID ADVANCE DIRECTIVES; CARE; FAMILY; INTERESTS; PHYSICIAN; SUPPORT; ENOUGH; PROXY; WANT AB To characterize how surrogates plan to make medical decisions for others. Descriptive study using semistructured qualitative interviews. Surrogates were interviewed by telephone from their homes. Fifty experienced surrogate decision-makers identified to make decisions for older, chronically ill veterans. Surrogates were asked to describe advance care planning conversations with loved ones and how they planned to make future medical decisions. Thematic content analysis was used to identify bases for decision-making. Surrogates described the motivators and the content of advance care planning conversations with loved ones. Surrogates described five bases for decision-making: (1) conversations (making decisions based on their knowledge of their loved ones' preferences), (2) relying on documents (referring to their loved ones' advance care directives), (3) shared experience (believing an "inner sense" would guide decisions because of shared lived experience with loved ones), (4) surrogates' own values and preferences about life, and (5) surrogates' network (enlisting the help of others). Although ethicists and clinicians expect surrogates to use substituted judgment or patients' best interests when making decisions, these data indicate that many surrogates rely on other factors such as their own best interests or mutual interests of themselves and the patient or intend to base substituted judgments on documents with which they have little familiarity. C1 VA Puget Sound Hlth Care Syst, Geriatr & Extended Care, Seattle, WA 98108 USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Vig, EK (reprint author), VA Puget Sound Hlth Care Syst, Geriatr & Extended Care, 1660 S Columbian Way S-182 Eth, Seattle, WA 98108 USA. EM vigster@u.washington.edu FU NIA NIH HHS [K23 AG19635] NR 31 TC 74 Z9 74 U1 3 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2006 VL 54 IS 11 BP 1688 EP 1693 DI 10.1111/j.1532-5415.2006.00911.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 100NS UT WOS:000241676400009 PM 17087695 ER PT J AU Hutt, E Ruscin, JM Corbett, K Radcliff, TA Kramer, AM Williams, EM Liebrecht, D Klenke, W Hartmann, S AF Hutt, Evelyn Ruscin, J. Mark Corbett, Kitty Radcliff, Tiffany A. Kramer, Andrew M. Williams, Elizabeth M. Liebrecht, Debra Klenke, William Hartmann, Sheryl TI A multifaceted intervention to implement guidelines improved treatment of nursing home-acquired pneumonia in a state veterans home SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nursing homes; pneumonia; veterans ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; MINIMUM DATA SET; RESIDENTS; MORTALITY; FACILITIES; INFLUENZA; REDUCE; HOSPITALIZATION; VACCINATION AB To assess the feasibility of a multifaceted strategy to translate evidence-based guidelines for treating nursing home-acquired pneumonia (NHAP) into practice using a small intervention trial. Pre-posttest with untreated control group. Two Colorado State Veterans Homes (SVHs) during two influenza seasons. Eighty-six residents with two or more signs of lower respiratory tract infection. Multifaceted, including a formative phase to modify the intervention, institutional-level change emphasizing immunization, and availability of appropriate antibiotics; interactive educational sessions for nurses; and academic detailing. Subjects' SVH medical records were reviewed for guideline compliance retrospectively for the influenza season before the intervention and prospectively during the intervention. Bivariate comparisons-of-care processes between the intervention and control facility before and after the intervention were made using the Fischer exact test. At the intervention facility, compliance with five of the guidelines improved: influenza vaccination, timely physician response to illness onset, x-ray for patients not being hospitalized, use of appropriate antibiotics, and timely antibiotic initiation for unstable patients. Chest x-ray and appropriate and timely antibiotics were significantly better at the intervention than at the control facility during the intervention year but not during the control year. Multifaceted, evidence-based, NHAP guideline implementation improved care processes in a SVH. Guideline implementation should be studied in a national sample of nursing homes to determine whether it improves quality of life and functional outcomes of this debilitating illness for long-term care residents. C1 Denver VA Med Ctr, Dept Med, Denver, CO 80220 USA. Denver VA Med Ctr, Nursing Serv, Denver, CO 80220 USA. Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Sch Pharm, Denver, CO 80202 USA. Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. RP Hutt, E (reprint author), Denver VA Med Ctr, Dept Med, 151,1055 Clermont St, Denver, CO 80220 USA. EM Evelyn.Hutt@uchsc.edu NR 35 TC 24 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2006 VL 54 IS 11 BP 1694 EP 1700 DI 10.1111/j.1532-5415.2006.00937.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 100NS UT WOS:000241676400010 PM 17087696 ER PT J AU Casarett, DJ Teno, J Higginson, I AF Casarett, David J. Teno, Joan Higginson, Irene TI How should nations measure the quality of end-of-life care for older adults? Recommendations for an international minimum data set SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID AFTER-DEATH INTERVIEWS; SUB-SAHARAN AFRICA; PALLIATIVE CARE; FAMILY-MEMBERS; DEVELOPING-COUNTRIES; TELEPHONE SURVEY; CANCER-PATIENTS; PUBLIC-HEALTH; HOSPICE CARE; ILL PATIENTS AB Nations face numerous challenges in providing high-quality end-of-life care for their citizens, and an aging population that has a prolonged trajectory of decline and substantial needs for care magnifies these challenges. As nations begin to address these challenges, it will be essential to determine whether their responses are effective, but current national data collection efforts are sporadic, and data are often collected only for patients who receive care through certain funding programs or provider organizations or in selected sites of care. Therefore, governments do not know whether their citizens are receiving adequate care, whether current programs are improving care, or how their outcomes compare with those of other countries. This article describes the importance of developing national minimum data sets that can be used to assess the quality of end-of-life care that older adults receive and recommends key variables that these data sets should include. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Brown Univ, Sch Med, Dept Med, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Community Hlth, Providence, RI 02912 USA. Kings Coll London, Sch Med & Dent, Dept Palliat Care & Policy, Rayne Inst, London WC2R 2LS, England. RP Casarett, DJ (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. EM Casarett@mail.med.upenn.edu NR 53 TC 31 Z9 31 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2006 VL 54 IS 11 BP 1765 EP 1771 DI 10.1111/j.1532-5415.2006.00925.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 100NS UT WOS:000241676400020 PM 17087706 ER PT J AU Schnelle, JF Ouslander, JG Simmons, SF AF Schnelle, John F. Ouslander, Joseph G. Simmons, Sandra F. TI Direct observations of nursing home care quality: Does care change when observed? SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article ID ENVIRONMENTAL INTERVENTION; REFLECT DIFFERENCES; FEEDING ASSISTANCE; WEIGHT-LOSS; RESIDENTS; INDICATOR; ACCURACY; DELIVERY; SLEEP AB Objectives: Recent research demonstrates that care recorded by nursing home (NH) staff is often inaccurate. Direct observations of care may therefore be of critical importance in assessing and improving care in this setting. Unfortunately, despite their apparent use in several types of quality assurance activities, there is little written information about the reliability or accuracy of observational procedures in NHs. This paper provides information about one important measurement issue (reactivity) that is often cited as a limitation of observational procedures in measuring usual care practices accurately. Design: Descriptive. Setting: Seven nursing homes. Participants: Staff and residents. Measurements: Direct observational time in bed; repositioning and feeding assistance. Results: Observational measures of care quality were stable over multiple observation periods and consistently detected quality problems even on the first and last days of observation. Conclusion: Direct observations of care provided to residents do not appear to change provider behavior. C1 Los Angeles Jewish Home Aging, Borun Ctr Gerontol Res, Reseda, CA 91335 USA. VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Div Geriatr, Los Angeles, CA 90024 USA. Emory Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Atlanta, GA USA. Emory Univ, Sch Med, Ctr Hlth Aging, Atlanta, GA USA. Atlanta VA Rehabil Res & Dev Ctr, Atlanta, GA USA. Birmingham Atlanta VA GRECC, Atlanta, GA USA. RP Schnelle, JF (reprint author), Los Angeles Jewish Home Aging, Borun Ctr Gerontol Res, 7150 Tampa Ave, Reseda, CA 91335 USA. EM JSchnell@ucla.edu FU NIA NIH HHS [AG10415] NR 16 TC 29 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD NOV PY 2006 VL 7 IS 9 BP 541 EP 544 DI 10.1016/j.jamda.2006.03.009 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 108VU UT WOS:000242268100001 PM 17095417 ER PT J AU Chun, J Chodosh, J AF Chun, Jeremy Chodosh, Joshua TI Controversy in heart failure management: Digoxin use in the elderly SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article ID NURSING-HOME PATIENTS; INVESTIGATION GROUP TRIAL; DIGITALIS WITHDRAWAL; EJECTION FRACTION; MORTALITY; MORBIDITY; ASSOCIATION; OUTCOMES; WOMEN C1 VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr & Gerontol, Los Angeles, CA USA. RP Chodosh, J (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jchodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 NR 35 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD NOV PY 2006 VL 7 IS 9 BP 581 EP 586 DI 10.1016/j.jamda.2006.08.010 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 108VU UT WOS:000242268100007 PM 17095423 ER PT J AU Poon, EG Blumenfeld, B Hamann, C Turchin, A Graydon-Baker, E McCarthy, PC Poikonen, J Mar, P Schnipper, JL Hallisey, RK Smith, S McCormack, C Paterno, M Coley, CM Karson, A Chueh, HC Van Putten, C Millar, SG Clapp, M Bhan, I Meyer, GS Gandi, TK Broverman, CA AF Poon, Eric G. Blumenfeld, Barry Hamann, Claus Turchin, Alexander Graydon-Baker, Erin McCarthy, Patricia C. Poikonen, John Mar, Perry Schnipper, Jeffrey L. Hallisey, Robert K. Smith, Sandra McCormack, Christine Paterno, Marilyn Coley, Christopher M. Karson, Andrew Chueh, Henry C. Van Putten, Cheryl Millar, Sally G. Clapp, Margaret Bhan, Ishir Meyer, Gregg S. Gandi, Tejal K. Broverman, Carol A. TI Design and implementation of an application and associated services to support interdisciplinary medication reconciliation efforts at an integrated healthcare delivery network SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Information-Association CY NOV 30-DEC 03, 2005 CL Austin, TX SP Amer Med Informat Assoc ID PATIENTS AFTER-DISCHARGE; ADVERSE EVENTS; DISCREPANCIES; ADMISSION; ERRORS; HISTORIES AB Confusion about patients' medication regimens during the hospital admission and discharge process accounts for many preventable and serious medication errors. Many organizations have begun to redesign their clinical processes to address this patient safety concern. Partners HealthCare, an integrated delivery network in Boston, Massachusetts, has answered this interdisciplinary challenge by leveraging its multiple outpatient electronic medical records (EMR) and inpatient computerized provider order entry (CPOE) systems to facilitate the process of medication reconciliation. This manuscript describes the design of a novel application and the associated services that aggregate medication data from EMR and CPOE systems so that clinicians can efficiently generate an accurate pre-admission medication list. Information collected with the use of this application subsequently supports the writing of admission and discharge orders by physicians, performance of admission assessment by nurses, and reconciliation of inpatient orders by pharmacists. Results from early pilot testing suggest that this new medication reconciliation process is well accepted by clinicians and has significant potential to prevent medication errors during transitions of care. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Partners Informat Syst, Wellesley, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Poon, EG (reprint author), Clin Informat Res & Dev, Suite 201,93 Worcester St, Wellesley, MA 02481 USA. EM epoon@partners.org NR 25 TC 46 Z9 51 U1 2 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2006 VL 13 IS 6 BP 581 EP 592 DI 10.1197/jamia.M2142 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 111CZ UT WOS:000242430300001 PM 17114640 ER PT J AU Bakken, S Grullon-Figueboa, L Izquierdo, R Lee, NJ Morin, P Palmas, W Teresi, J Weinstock, RS Shea, S Starren, J AF Bakken, Suzanne Grullon-Figueboa, Lorena Izquierdo, Roberto Lee, Nam-Ju Morin, Philip Palmas, Walter Teresi, Jeanne Weinstock, Ruth S. Shea, Steven Starren, Justin CA IDEATEL Consortium TI Development, validation, and use of English and Spanish versions of the Telemedicine Satisfaction and Usefulness Questionnaire SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PATIENT SATISFACTION; HEALTH-CARE; DIABETES EDUCATION; TELEDERMATOLOGY; OUTCOMES; TRIAL; HOME AB Objectives: To describe the development and validation of low literacy English and Spanish versions of the 26-item Telemedicine Satisfaction and Usefulness Questionnaire (TSUQ), report telemedicine satisfaction and usefulness ratings of urban and rural participants in the Informatics for Diabetes Education and Telemedicine (IDEATel) project, and explore relationships between utilization and perceptions of satisfaction and usefulness. Methods: Data sources included TSUQ, utilization data from IDEATel log files, and sociodemographic data from the annual IDEATel interview. Psychometric analyses were conducted to examine the reliability and validity of TSUQ. Data were analyzed using descriptive, correlational techniques. Results: The principal components factor analysis extracted two factors (Video Visits, alpha = .96, and. Use and Impact, alpha = .92) that explained 63.6% of the variance in TSUQ satisfaction scores. All satisfaction and usefulness items had mean scores of greater than 4 on a 5-point scale. Those from urban areas reported significantly higher ratings on both factors than rural participants as did those who did not know how to use a computer at baseline. Mean frequency of utilization of IDEATel components was highest for blood sugar testing followed by web site for reviewing results, blood pressure testing, video visits, and ADA educational Web pages. Associations between utilization and perceptions of satisfaction and usefulness varied among IDEATel components. Conclusion: Psychometric analyses support the construct validity and internal consistency reliability of TSUQ, which is available in both English and Spanish at a readability level of 8th grade. Both rural and urban participants reported high levels of satisfaction and found all IDEATel components useful. Further work is needed to examine the relationships between utilization and perceptions of satisfaction and usefulness and to explore the effects of location (urban versus rural) and ethnicity on satisfaction with telemedicine services. C1 Columbia Univ, Sch Nursing, New York, NY 10032 USA. Columbia Univ, Dept Biomed Informat, New York, NY USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY USA. Columbia Univ, Dept Med, New York, NY USA. Hebrew Home Aged, Div Res, Bronx, NY USA. Columbia Univ, Stroud Ctr, New York, NY USA. VA Med Ctr, Dept Vet Affairs, Syracuse, NY USA. Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. Columbia Univ, Dept Radiol, New York, NY 10027 USA. RP Bakken, S (reprint author), Columbia Univ, Sch Nursing, 617 W 168th St, New York, NY 10032 USA. EM Suzanne.Bakken@dbmi.columbia.edu FU NINR NIH HHS [P20 NR007799] NR 30 TC 41 Z9 42 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2006 VL 13 IS 6 BP 660 EP 667 DI 10.1197/jamia.M2146 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 111CZ UT WOS:000242430300010 PM 16929036 ER PT J AU Mele, D Soukhomovskaia, O Pacchioni, E Merli, E Avigni, N Federici, L Levine, RA Ferrari, R AF Mele, Donato Soukhomovskaia, Olga Pacchioni, Emanuele Merli, Elisa Avigni, Nicola Federici, Luca Levine, Robert A. Ferrari, Roberto TI Improved detection of left ventricular thrombi and spontaneous echocontrast by tissue harmonic imaging in patients with myocardial infarction SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID SPONTANEOUS ECHO CONTRAST; 2 DIMENSIONAL ECHOCARDIOGRAPHY; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; LEFT ATRIAL THROMBUS; MURAL THROMBI; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; 2-DIMENSIONAL ECHOCARDIOGRAPHY; NATURAL-HISTORY; APICAL THROMBI; DIAGNOSIS AB Background. Tissue harmonic imaging (THI) reduces near-field and side-lobe artifacts. This could improve recognition of cardiac masses, including thrombi and spontaneous echocontrast (SEC), a known thromboembolic risk factor. Objectives. We tested the hypothesis that THI improves detection of left ventricular (LV) thrombi and SEC compared with transthoracic fundamental imaging in patients with recent myocardial infarction. Methods: In all, 118 consecutive patients with recent myocardial infarction were studied at predischarge. The echocardiographic examination was performed in both fundamental imaging and THI modality and evaluated by 3 skilled and 3 nonexperienced observers for recognition of LV thrombosis and SEC. Results: THI increased LV thrombi diagnosis by 25% by skilled observers and by 50% by nonexperienced readers, reducing the number of false-positive diagnoses by 67%. Also, compared with fundamental imaging, THI improved recognition of LV SEC by both experienced and nonexperienced observers by 56% and 62%, respectively. Conclusions. The improved recognition of LV thrombosis and SEC by THI in patients with myocardial infarction is clinically relevant allowing appropriate treatment and prognostic stratification. Therefore, routine use of THI should he recommended when studying such patients in clinical practice. C1 Azienda Osped Univ Ferrara, Cardiol Unit, I-44100 Ferrara, Italy. Fdn IRCCS, Ctr Fisiopatol Cardiovasc Salvatore Maugeri, Ferrara, Italy. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Mele, D (reprint author), Azienda Osped Univ Ferrara, Cardiol Unit, Corso Giovecca 203, I-44100 Ferrara, Italy. EM donatomele@libero.it NR 53 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 2006 VL 19 IS 11 BP 1373 EP 1381 DI 10.1016/j.echo.2006.05.011 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 109AQ UT WOS:000242280700012 PM 17098141 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI ACE2: A new target for prevention of diabetic nephropathy? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID ANGIOTENSIN-CONVERTING ENZYME; GENE-EXPRESSION C1 Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Yawkey 6C,55 Fruit St, Boston, MA 02114 USA. EM jingelfinger@partners.org NR 17 TC 15 Z9 21 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 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2006 VL 17 IS 11 BP 2957 EP 2959 DI 10.1681/ASN.2006090986 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 103UL UT WOS:000241912100003 PM 17021263 ER PT J AU Regan, MM Viale, G Mastropasqua, MG Maiorano, E Golouh, R Carbone, A Brown, B Suurkula, M Langnan, G Mazzucchelli, L Braye, S Grigolato, P Gelber, RD Castiglione-Gertsch, M Price, KN Coates, AS Goldhirsch, A Gusterson, B AF Regan, Meredith M. Viale, Giuseppe Mastropasqua, Mauro G. Maiorano, Eugenio Golouh, Rastko Carbone, Antonino Brown, Bob Suurkula, Mart Langnan, Gerald Mazzucchelli, Luca Braye, Stephen Grigolato, Piergiovanni Gelber, Richard D. Castiglione-Gertsch, Monica Price, Karen N. Coates, Alan S. Goldhirsch, Aron Gusterson, Barry CA Int Breast Canc Study Grp TI Re-evaluating adjuvant breast cancer trials: Assessing hormone receptor status by immunohistochemical versus extraction assays SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LIGAND-BINDING ASSAY; INTERNATIONAL EXPERT CONSENSUS; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; PREDICTING RESPONSE; RANDOMIZED-TRIALS; STEROID-RECEPTORS; PRIMARY THERAPY; CARCINOMA; CHEMOTHERAPY AB Background. Tumor levels of steroid hormone receptors, a factor used to select adjuvant treatment for early-stage breast cancer, are currently determined with immunohistochemical assays. These assays have a discordance of 10%-30% with previously used extraction assays. We assessed the concordance and predictive value of hormone receptor status as determined by immunohistochemical and extraction assays on specimens from International Breast Cancer Study Group Trials VIII and IX. These trials predominantly used extraction assays and compared adjuvant chemoendocrine therapy with endocrine therapy alone among pre- and postmenopausal patients with lymph node-negative breast cancer. Trial conclusions were that combination therapy provided a benefit to pre- and postmenopausal patients with estrogen receptor (ER)-negative tumors but not to ER-positive postmenopausal patients. ER-positive premenopausal patients required further study. Methods: Tumor specimens from 571 premenopausal and 976 postmenopausal patients on which extraction assays had determined ER and progesterone receptor (PgR) levels before randomization from October 1, 1988, through October 1, 1999, were re-evaluated with an immunohistochernical assay in a central pathology laboratory. The endpoint was disease-free survival. Hazard ratios of recurrence or death for treatment comparisons were estimated with Cox proportional hazards regression models, and discriminatory ability was evaluated with the c index. All statistical tests were two-sided. Results: Concordance of hormone receptor status determined by both assays ranged from 74% (kappa = 0.48) for PgR among postmenopausal patients to 88% (kappa = 0.66) for ER in postmenopausal patients. Hazard ratio estimates were similar for the association between disease-free survival and ER status (among all patients) or PgR status (among postmenopausal patients) as determined by the two methods. However, among premenopausal patients treated with endocrine therapy alone, the discriminatory ability of PgR status as determined by immunohistochemical assay was statistically significantly better (c index = 0.60 versus 0.51; P =.003) than that determined by extraction assay, and so immunohistochemically determined PgR status could predict disease-free survival. Conclusions: Trial conclusions in which ER status (for all patients) or PgR status (for postmenopausal patients) was determined by immunohistochemical assay supported those determined by extraction assays. However, among premenopausal patients, trial conclusions drawn from PgR status differed-immunohistochemically determined PgR status could predict response to endocrine therapy, unlike that determined by the extraction assay. C1 Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Milan, Dept Pathol, European Inst Oncol, Milan, Italy. Univ Bari, Dept Pathol, Bari, Italy. Ctr Riferimento Oncol, Div Pathol, I-33081 Aviano, Italy. Inst Oncol, Ljubljana, Slovenia. Ist Nazl Tumori, Dept Pathol, I-20133 Milan, Italy. Melbourne Pathol, Collingwood, Vic, Australia. Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden. Univ Cape Town, Dept Anat Pathol, ZA-7925 Cape Town, South Africa. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Univ Bern, Bern Inst Pathol, Bern, Switzerland. Swiss Grp Clin Canc Res, Bern, Switzerland. Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. John Hunter Hosp, Hunter Area, Pathol Serv, New Lambton Heights, NSW, Australia. Oncol Med Spedali Civili, Brescia, Italy. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. IBCSG Coordinating Ctr, Bern, Switzerland. Univ Sydney, Canc Council Australia, Australian New Zealand Breast Canc Trials Grp, Sydney, NSW 2006, Australia. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. Oncol Inst So Switzerland, Lugano, Mendrisio, Switzerland. European Inst Oncol, Milan, Italy. Univ Glasgow, Western Infirm, Div Canc Sci & Mol Pathol, Glasgow, Lanark, Scotland. Dana Farber Canc Inst, IBCSG, Ctr Stat, Boston, MA 02115 USA. RP Regan, MM (reprint author), Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM mregan@jimmy.harvard.edu RI gusterson, barry/D-3752-2009; Maiorano, Eugenio/F-1382-2015 FU NCI NIH HHS [CA-75362] NR 32 TC 96 Z9 98 U1 1 U2 3 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 NOV 1 PY 2006 VL 98 IS 21 BP 1571 EP 1581 DI 10.1093/jnci/djj415 PG 11 WC Oncology SC Oncology GA 110LE UT WOS:000242379600012 PM 17077359 ER PT J AU Christiani, DC Pao, W DeMartini, JC Linnoila, RI Malkinson, AM Onn, A Politi, KA Sharp, M Kwok-Kim AF Christiani, David C. Pao, William DeMartini, James C. Linnoila, R. Ilona Malkinson, Alvin M. Onn, Amir Politi, Katerina A. Sharp, Michael Kwok-Kim TI BAC Consensus Conference, November 4-6. 2004: Epidemiology, pathogenesis, and preclinical models SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Bronchioloalveolar Cell Carcinoma (BAC) CY NOV 04-06, 2004 CL New York, NY SP Int Assoc Study Lung Canc, Amer Soc Clin Oncol DE bronchioloalveolar carcinoma; preclinical models; epidemiology; pathogenesis; lung cancer ID JAAGSIEKTE SHEEP RETROVIRUS; OVINE PULMONARY ADENOCARCINOMA; HUMAN LUNG-CANCER; K-RAS ONCOGENE; EPIDERMAL-GROWTH-FACTOR; ATHYMIC NUDE-MICE; BRONCHIOLOALVEOLAR CARCINOMA; CONDITIONAL EXPRESSION; CELL-LINE; BUTYLATED HYDROXYTOLUENE AB Introduction: Human bronchioloalveolar carcinoma (BAC) is a disease with an evolving definition. "Pure" BAC, characterized by a bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion, represents only 2 to 6% of non-small cell lung cancer (NSCLC) cases, but up to 20% of NSCLC cases may contain elements of BAC. This imprecise definition makes it difficult to perform epidemiologic analyses or to generate accurate animal models. However, because BAC appears to behave clinically differently from adenocarcinoma, a better understanding of this disease entity is imperative. Methods/Results: At the BAC Consensus Conference in 2004, our committee discussed issues relevant to BAC epidemiology, pathogenesis, and preclinical models. Conclusions: Elucidation of molecular events involved in BAC tumorigenesis will allow for more precise epidemiologic studies and improved animal models, which will enable development of more effective treatments against the disease. C1 Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10021 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. NCI, Rockville, MD USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Texas, MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. Vet Labs Agcy, Dept Pathol, Penicuik, Midlothian, Scotland. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pao, W (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, 1275 York Ave, New York, NY 10021 USA. EM paow@mskcc.org RI Sharp, Mike/D-1467-2009; APHA, Staff publications/E-6082-2010 FU NCI NIH HHS [CA 092824, CA 074386, CA 0940578, CA 59116]; NIA NIH HHS [K08AG 2400401] NR 80 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2006 VL 1 IS 9 SU S BP S2 EP S7 DI 10.1097/01243894-200611001-00002 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 110AM UT WOS:000242350700002 PM 17409996 ER PT J AU Travis, WD Garg, K Franklin, WA Wistuba, II Sabloff, B Noguchi, M Kakinuma, R Zakowski, M Ginsberg, M Padera, R Jacobson, F Johnson, BE Hirsch, F Brambilla, E Flieder, DB Geisinger, KR Thunnissen, F Kerr, K Yankelevitz, D Franks, TJ Galvin, JR Henderson, DW Nicholson, AG Hasleton, PS Roggli, V Tsao, MS Cappuzzo, F Vazquez, M AF Travis, William D. Garg, Kavita Franklin, Wilbur A. Wistuba, Ignacio I. Sabloff, Bradley Noguchi, Masayuki Kakinuma, Ryutaro Zakowski, Maureen Ginsberg, Michelle Padera, Robert Jacobson, Francine Johnson, Bruce E. Hirsch, Fred Brambilla, Elizabeth Flieder, Douglas B. Geisinger, Kim R. Thunnissen, Frederik Kerr, Keith Yankelevitz, David Franks, Teri J. Galvin, Jeffrey R. Henderson, Douglas W. Nicholson, Andrew G. Hasleton, Philip S. Roggli, Victor Tsao, Ming-Sound Cappuzzo, Federico Vazquez, Madeline TI Bronchioloalveolar carcinoma and lung adenocarcinoma: The clinical importance and research relevance of the 2004 World Health Organization pathologic criteria SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Bronchioloalveolar Cell Carcinoma (BAC) CY NOV 04-06, 2004 CL New York, NY SP Int Assoc Study Lung Canc, Amer Soc Clin Oncol DE lung cancer; adenocarcinoma; bronchioloalveolar carcinoma; pathology; radiology; classification ID HIGH-RESOLUTION CT; GROUND-GLASS OPACITY; THIN-SECTION CT; PERIPHERAL ADENOCARCINOMA; PROGNOSTIC-SIGNIFICANCE; COMPUTED-TOMOGRAPHY; RECEPTOR GENE; CANCER; GEFITINIB; SURVIVAL AB Introduction: Advances in the pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC) have demonstrated important new prognostic features that have led to changes in classification and diagnostic criteria. Methods: The literature and a set of cases were reviewed by a pathology/CT review panel of pathologists and radiologists who met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The group addressed the question of whether sufficient data exist to modify the 2004 World Health Organization (WHO) classification of adenocarcinoma and BAC to define a "minimally invasive" adenocarcinoma with BAC. The problems of diffuse and/or multicentric BAC and adenocarcinoma were evaluated. Results: The clinical concept of BAC needs to be reevaluated with careful attention to the new 2004 WHO criteria because of the major clinical implications. Existing data indicate that patients with solitary, small, peripheral BAC have a 100% 5-year survival rate. The favorable prognostic impact of the restrictive criteria for BAC is already being detected in major epidemiologic data sets such as the Surveillance Epidemiology and End-Results registry. Most lung adenocarcinomas, including those with a BAC component, are invasive and consist of a mixture of histologic patterns. Therefore, they are best classified as adenocarcinoma, mixed subtype. This applies not only to adenocarcinomas with a solitary nodule presentation but also to tumors with a diffuse/multinodular pattern. The percentage of BAC versus invasive components in lung adenocarcinomas seems to be prognostically important. However, at the present time, a consensus definition of "minimally invasive" BAC with a favorable prognosis was not recommended by the panel, so the 1999/2004 WHO criteria for BAC remain unchanged. In small biopsy specimens or cytology specimens, recognition of a BAC component is possible. However, it is not possible to exclude an invasive component. The diagnosis of BAC requires thorough histologic sampling of the tumor. Conclusion: Advances in understanding of the pathology and CT features of BAC and adenocarcinoma have led to important changes in diagnostic criteria and classification of BAC and adenocarcinoma. These criteria need to be uniformly applied by pathologists, radiologists, clinicians, and researchers. The 2004 WHO classification of adenocarcinoma is readily applicable to research studies, but attention needs to be placed on the relative proportion of the adenocarcinoma subtypes. Other recently recognized prognostic features such as size of scar, size of invasive component, or pattern of invasion also seem to be important. More work is needed to determine the most important prognostic pathologic features in lung adenocarcinoma. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Tsukuba, Ibaraki 305, Japan. Natl Canc Ctr, Canc Screening Technol Div, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Dept Oncol, Denver, CO USA. CHU Grenoble, Dept Pathol, Serv Pathol Cellulaire, F-38043 Grenoble, France. Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. Canisus Wihelmina Ziekenhuis, Dept Pathol, Nijmegen, Netherlands. Univ Aberdeen, Sch Med, Dept Pathol, Aberdeen AB9 2ZD, Scotland. New York Hosp Cornell UMC, Dept Radiol, New York, NY USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Univ Maryland, Dept Radiol, Baltimore, MD 21201 USA. Flinders Med Ctr, Dept Pathol, Bedford Pk, SA, Australia. Brompton Hosp, Dept Pathol, London SW3 6HP, England. Univ Manchester, Wythenshawe Hosp, Dept Pathol, Manchester M13 9PL, Lancs, England. Duke Univ, Dept Pathol, Durham, NC 27706 USA. Princess Margaret Hosp, Univ Hlth Network, Dept Pathol, Toronto, ON M4X 1K9, Canada. Bellaria Hosp Med Oncol, Bologna, Italy. New York Hosp Cornell UMC, Dept Pathol, New York, NY USA. RP Travis, WD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM travisw@mskcc.org RI Brambilla, Elisabeth/L-8796-2013 NR 43 TC 86 Z9 93 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2006 VL 1 IS 9 SU S BP S13 EP S19 DI 10.1097/01243894-200611001-00004 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 110AM UT WOS:000242350700004 PM 17409995 ER PT J AU Wislez, M Beer, DG Wistuba, I Cadranel, J Saijo, N Johnson, BE AF Wislez, Marie Beer, David G. Wistuba, Ignacio Cadranel, Jacques Saijo, Nagahiro Johnson, Bruce E. TI Molecular biology, genomics, and proteomics in bronchioloalveolar carcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Bronchioloalveolar Cell Carcinoma (BAC) CY NOV 04-06, 2004 CL New York, NY SP Int Assoc Study Lung Canc, Amer Soc Clin Oncol DE lung neoplasm; adenocarcinoma; bronchioloalveolar; adenocarcinoma; carcinoma; non-small cell lung cancer ID ATYPICAL ADENOMATOUS HYPERPLASIA; PERIPHERAL LUNG ADENOCARCINOMA; RECEPTOR GENE-MUTATIONS; K-RAS MUTATIONS; PULMONARY ADENOCARCINOMA; ACTIVATING MUTATIONS; EXPRESSION; SUBTYPE; GEFITINIB; SURVIVAL AB The charge of the Molecular Biology, Genomics, and Proteomics in Bronchioloalveolar Carcinoma Committee was to evaluate the molecular biology, genomic changes, and proteomic findings in patients with bronchioloalveolar carcinoma compared with other types of lung cancer. The literature was reviewed and unpublished information was presented by the committee members at the session. The molecular biology studies have included findings on epidermal growth factor receptor (EGFR) mutations, p53 mutations, K-ras mutations, and loss of heterozygosity. The genomic changes have mostly focused on the mRNA expression arrays as well as protein studies. The current state of knowledge was reviewed, the missing information was acknowledged, and proposals for future research were identified. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Univ Paris 06, Hop Tenon, APHP, Serv Pneumol & Reanimat Resp, Paris, France. Univ Paris 06, Lab Biol Cellulaire & Immunopathol Pulm, Paris, France. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Natl Canc Ctr E, Kashiwa, Chiba, Japan. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM bruce_johnson@dfci.harvard.edu NR 42 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2006 VL 1 IS 9 SU S BP S8 EP S12 DI 10.1097/01243894-200611001-00003 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 110AM UT WOS:000242350700003 PM 17410000 ER PT J AU Liddicoat, RV Zheng, H Internicola, J Werner, BG Kazianis, A Golan, Y Rubinstein, EP Freedberg, KA Walensky, RP AF Liddicoat, Rebecca V. Zheng, Hui Internicola, Jeanne Werner, Barbara G. Kazianis, Arthur Golan, Yoav Rubinstein, Eric P. Freedberg, Kenneth A. Walensky, Rochelle P. TI Implementing a routine, voluntary HIV testing program in a Massachusetts county prison SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE HIV; HIV testing; prison; screening ID VIRUS; PREVALENCE; INMATES AB Although U.S. prison inmates have higher rates of HIV infection than the general population, most inmates are not routinely tested for HIV infection at prison entry. The study objective was to implement a routine, voluntary HIV testing program in a Massachusetts county prison. During admission, inmates were given group HIV pretest counseling and were subsequently offered private HIV testing. This intervention was compared to a control period during which HIV testing was provided only upon inmate or physician request. Between November 2004 and April 2005, 1,004 inmates met inclusion criteria and were offered routine, voluntary HIV testing. Of these, 734 (73.1%) accepted, 2 (0.3%) were HIV-infected, and 457 (45.5%) bad been tested for HIV in the previous year. The testing rate of 73.1% was significantly increased from the rate of 18.0% (318 of 1,723) during the control period (p < 0.001). Among the inmates tested for HIV in the prior year, 78.2% bad received their last HIV test in the prison setting. Careful attention should be paid to prevent redundancy of testing efforts in the prison population. Implementing a routine HIV testing program among prison inmates greatly increased testing rates compared to on-request testing. C1 Greater Los Angeles Vet Adm, Dept Med, Los Angeles, CA 90073 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Gen Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Partners AIDS Res Ctr, Boston, MA USA. Suffolk Cty House Correct, Boston, MA USA. Tufts Univ, Sch Med, Dept Infect Dis, Boston, MA 02111 USA. Massachusetts Dept Publ Hlth, HIV AIDS Bur, Boston, MA USA. Massachusetts State Lab Inst, Boston, MA USA. RP Liddicoat, RV (reprint author), Greater Los Angeles Vet Adm, Dept Med, Mail 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rebecca.liddicoat@med.va.gov OI Walensky, Rochelle P./0000-0002-8795-379X FU NCI NIH HHS [F32 CA090073]; NIAID NIH HHS [K24 AI062476, R01 AI042006, R01 AI42006, P30 AI060354, K23 AI01794, K23 AI001794]; NIMH NIH HHS [R01 MH065869, R01 MH65869]; PHS HHS [T32 HP11001] NR 10 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD NOV PY 2006 VL 83 IS 6 BP 1127 EP 1131 DI 10.1007/s11524-006-9095-9 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 121UG UT WOS:000243181900012 PM 16897416 ER PT J AU Daskivich, TJ Regan, MM Oh, WK AF Daskivich, Timothy J. Regan, Meredith M. Oh, William K. TI Prostate specific antigen doubling time calculation: Not as easy as 1, 2, 4 SO JOURNAL OF UROLOGY LA English DT Review DE prostate; prostate-specific antigen; prostatic neoplasms; decision support techniques ID CANCER-SPECIFIC MORTALITY; SURROGATE END-POINT; RADICAL PROSTATECTOMY; RADIATION-THERAPY; NATURAL-HISTORY; CLINICAL-TRIALS; WORKING GROUP; PSA VELOCITY; RECURRENCE; GUIDELINES AB Purpose: Although prostate specific antigen doubling time is widely used to predict outcomes such as time to progression and prostate cancer specific mortality, clinicians may be unaware of the impact of method on prostate specific antigen doubling time calculation. We present a critical review of the literature to assess the diversity of methods used to calculate prostate specific antigen doubling time. We then describe the need for methodological consistency with the literature by showing examples from our clinical experience at our institution. Materials and Methods: A comprehensive review of articles evaluating prostate specific antigen doubling time as a prognostic and predictive indicator in various prostate cancer disease states was performed using PubMed. Case examples were drawn from the prostate cancer database at our institution. The database is a registry of 4,651 patients with prostate cancer who have been seen at our institution since 1998. Results: The methodology of prostate specific antigen doubling time calculation is inconsistent in the literature. Based on our experience and data presented in the literature the different methods in the literature are not always interchangeable. Small deviations from the methods outlined in a study can sometimes lead to wide variation in calculated prostate specific antigen doubling time. This variation of up to several months or longer is large enough to cause errors in assessment of prognosis and can even lead to incorrect management. The rules for prostate specific antigen doubling time calculation found in the literature can be categorized into 4 parameter groups, including method, calculation interval, data acquisition rules and data analysis rules. Case examples illustrate the importance of adherence to the literature with regard to each parameter. Conclusions: Consistency with the literature in methodological elements of prostate specific antigen doubling time calculation is essential for the accurate calculation of prostate specific antigen doubling time. Clinicians and researchers should understand how methodological differences influence the value of calculated prostate specific antigen doubling time for purposes of patient care and research. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dana Bldg Room 1230,44 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 31 TC 26 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2006 VL 176 IS 5 BP 1927 EP 1937 DI 10.1016/j.juro.2006.07.002 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 094XR UT WOS:000241273100008 PM 17070213 ER PT J AU Hunter, S Samir, A Eisner, B Gervais, D Maher, M Hahn, P McGovern, F Mueller, P AF Hunter, Scott Samir, Anthony Eisner, Brian Gervais, Debra Maher, Michael Hahn, Peter McGovern, Francis Mueller, Peter TI Diagnosis of renal lymphoma by percutaneous image guided biopsy: Experience with 11 cases SO JOURNAL OF UROLOGY LA English DT Article DE kidney; lymphoma; biopsy; nephrectomy; radiology; interventional ID COMPUTED-TOMOGRAPHY; HELICAL CT; NEEDLE; TUMORS; MASSES; SIZE AB Purpose: We reviewed an institutional experience with image guided percutaneous biopsy of focal renal masses that yielded a diagnosis of lymphoma. Materials and Methods: We retrospectively reviewed the hospital records of patients undergoing percutaneous renal biopsy between September 1997 and February 2005. Results: A total of 407 image guided focal renal lesion biopsies were identified. A diagnosis of lymphoma was made in 11 patients (3%). Biopsies were performed under computerized tomography guidance in 9 cases (82%) and under ultrasound guidance in 2 (18%). Core biopsies were performed in 11 cases, while fine needle aspiration was done in 10 (9 1%). Fine needle aspirations underwent cytological analysis in 10 cases and flow cytometry analysis in 9. The final combined pathological diagnoses were B-cell lymphoma in 10 cases and lymphomatoid granulomatosis in 1. Analysis of core biopsies yielded a diagnosis of B-cell lymphoma in 10 cases (91%) and lymphomatoid granulomatosis in 1. Analysis of fine needle aspirations yielded a diagnosis of B-cell lymphoma in 3 cases (30%), lymphoma in 4 (40%), suspicion of lymphoma in 1 (10%), atypical cells in 1 (10%) and a nondiagnostic sample in 1 (10%). Flow cytometry concurred with cytology in the diagnosis of B-cell lymphoma in 2 cases, allowed the identification of lymphoma subtype, which was not made on cytology, in 4, was insufficient in 2 and identified no abnormality in 1. No patients underwent surgery or an ablative procedure. Conclusions: Core biopsy has a higher diagnostic yield than fine needle aspiration for diagnosing renal lymphoma. Flow cytometry analysis adds additional diagnostic information to cytological examination of fine needle aspiration samples. Accurate diagnosis of lymphoma in these cases allowed proper treatment without unnecessary surgery or other procedures. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Gervais, D (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM dgervais@partners.org NR 15 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2006 VL 176 IS 5 BP 1952 EP 1956 DI 10.1016/j.juro.2006.07.032 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 094XR UT WOS:000241273100011 PM 17070216 ER PT J AU Matin, SF Ahrar, K Cadeddu, JA Gervais, DA McGovern, FJ Zagoria, RA Uzzo, RG Haaga, J Resnick, MI Kaouk, J Gill, IS AF Matin, Surena F. Ahrar, Kamran Cadeddu, Jeffrey A. Gervais, Debra A. McGovern, Francis J. Zagoria, Ronald A. Uzzo, Robert G. Haaga, John Resnick, Martin I. Kaouk, Jihad Gill, Inderbir S. TI Residual and recurrent disease following renal energy ablative therapy: A multi-institutional study SO JOURNAL OF UROLOGY LA English DT Article DE cryotherapy; catheter ablation; carcinoma; renal cell; diagnostic imaging; evidence-based medicine ID GUIDED RADIOFREQUENCY ABLATION; RADIO-FREQUENCY ABLATION; TUMORS; MASSES; COMPLICATIONS; CRYOABLATION AB Purpose: In this study we detail the incidence and pattern of residual and recurrent disease after radio frequency ablation or cryoablation of a renal mass and, using this information, determine reasonable minimum recommendations for when to perform surveillance imaging during year 1 after treatment. To our knowledge no evidence based guidelines exist for determining how or when followup abdominal imaging should be performed after renal energy ablative therapy. Materials and Methods: We reviewed treatment and followup information of patients who underwent radio frequency ablation or cryoablation for a renal mass at 7 institutions. Postoperative monitoring was performed using a variety of surveillance schedules. Results: Of 616 patients 63 were found to have residual or recurrent disease after primary radio frequency ablation (13.4%) or cryoablation (3.9%) for a median of 8.7% in 7 institutions. Most incomplete treatments (70%) were detected within the first 3 months. After salvage ablative therapy was rendered, therapy failed in only 4.2%. At a mean followup of 2 years patients with residual or recurrent disease had an overall survival rate of 82.5% and a 2-year metastasis-free survival rate of 97.4% for those with localized, unilateral renal tumors. Conclusions: In most cases initial treatment failure was detected within the first 3 months after treatment. Our findings support a minimum of 3 to 4 imaging studies in year I after ablative therapy, and at months 1, 3, 6 (optional) and 12. C1 Univ Texas, MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Intervent Radiol, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Urol, Dallas, TX USA. Massachusetts Gen Hosp, Dept Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Wake Forest Univ, Baptist Med Ctr, Dept Radiol, Winston Salem, NC 27109 USA. Fox Chase Canc Ctr, Dept Urol, Philadelphia, PA 19111 USA. Case Western Reserve Univ, Dept Urol, Glick Urol Inst, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Matin, SF (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Urol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM surmatin@mdanderson.org OI Zagoria, Ronald/0000-0001-6926-4627 NR 13 TC 106 Z9 112 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2006 VL 176 IS 5 BP 1973 EP 1977 DI 10.1016/j.juro.2006.07.016 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 094XR UT WOS:000241273100019 PM 17070224 ER PT J AU D'Amico, AV Barry, MJ AF D'Amico, Anthony V. Barry, Michael J. TI Prostate cancer prevention and finasteride SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; finasteride; prostatic hyperplasia ID PSA VELOCITY; RISK; STATISTICS; THERAPY; DEATH AB Purpose: We assessed whether the association between the larger changes in prostate specific antigen and high grade prostate cancer observed in the Prostate Cancer Prevention Trial can explain the increased detection of high grade prostate cancer in men randomized to finasteride vs placebo. Materials and Methods: A literature review was performed to obtain evidence to develop a hypothesis that may explain the results of the Prostate Cancer Prevention Trial. Results: On average finasteride halved prostate specific antigen. As shown by the Medical Therapy of Prostatic Symptoms study and Prostate Cancer Prevention Trial, it also decreased the annual median increase in prostate specific antigen from benign prostatic hyperplasia. Therefore, despite doubling prostate specific antigen during the first 3 years of the Prostate Cancer Prevention Trial, to have prostate specific antigen exceed 4 ng/ml and have a prostate biopsy recommended men receiving finasteride vs placebo required greater increases in prostate specific antigen, which was shown in the Prostate Cancer Prevention Trial to be associated with high grade disease (p < 0.001). Also, the decrease of the contribution to prostate specific antigen from benign prostatic hyperplasia by finasteride improved the performance characteristics of prostate specific antigen to detect Gleason score 7 or higher prostate cancer. Conclusions: By decreasing the contribution to prostate specific antigen from benign prostatic hyperplasia finasteride makes changes in prostate specific antigen more cancer specific. This effect may explain the increased detection of high grade prostate cancer in men randomized to finasteride in the Prostate Cancer Prevention Trial. How to best use prostate specific antigen to recommend biopsy in men on 5 alpha-reductase inhibitors requires further study. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 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@lroc.harvard.edu NR 10 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2006 VL 176 IS 5 BP 2010 EP 2012 DI 10.1016/j.juro.2006.07.045 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 094XR UT WOS:000241273100033 PM 17070238 ER PT J AU Kanai, R Kar, K Anthony, K Gould, LH Ledizet, M Fikrig, E Marasco, WA Koski, RA Modis, Y AF Kanai, Ryuta Kar, Kalipada Anthony, Karen Gould, L. Hannah Ledizet, Michel Fikrig, Erol Marasco, Wayne A. Koski, Raymond A. Modis, Yorgo TI Crystal structure of West Nile virus envelope glycoprotein reveals viral surface epitopes SO JOURNAL OF VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; SEMLIKI-FOREST-VIRUS; DENGUE VIRUS; DC-SIGN; DOMAIN-III; CARBOHYDRATE-RECOGNITION; MEMBRANE-FUSION; PROTEIN; BINDING; ANTIBODY AB West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics. C1 Yale Univ, Bass Ctr Struct Biol, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. L2 Diagnost, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Modis, Y (reprint author), 266 Whitney Ave,Bass 430, New Haven, CT 06520 USA. EM yorgo.modis@yale.edu OI Modis, Yorgo/0000-0002-6084-0429 FU NIAID NIH HHS [R41-AI060217, R41 AI060217, R41 AI068154, R41-AI068154-01, U01 AI061361, U01-AI061361] NR 42 TC 139 Z9 149 U1 3 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2006 VL 80 IS 22 BP 11000 EP 11008 DI 10.1128/JVI.01735-06 PG 9 WC Virology SC Virology GA 102OI UT WOS:000241821300010 PM 16943291 ER PT J AU Kasprowicz, V Isa, A Tolfvenstam, T Jeffery, K Bowness, P Klenerman, P AF Kasprowicz, Victoria Isa, Adiba Tolfvenstam, Thomas Jeffery, Katie Bowness, Paul Klenerman, Paul TI Tracking of peptide-specific CD4(+) T-cell responses after an acute resolving viral infection: a study of parvovirus B19 SO JOURNAL OF VIROLOGY LA English DT Article ID CANDIDATE RECOMBINANT VACCINE; MEDIATED INTERFERON-GAMMA; HEPATITIS-C; CLASS-I; VIRUS; ARTHRITIS; HLA; EXPRESSION; CHILDREN; LEUKEMIA AB The evolution of peptide-specific CD4(+) T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4(+) T-cell response to the two B19 capsid proteins were investigated using a set of overlapping peptides and gamma interferon-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells (PBMCs) from a cohort of acutely infected individuals who presented with acute arthropathy. These were compared to those for a cohort of B19-specific immunoglobulin M-negative (IgM(-)), IgG(+) remotely infected individuals. Both cohorts of individuals were found to make broad CD4(+) responses. However, while the responses following acute infection were detectable ex vivo, responses in remotely infected individuals were only detected after culture. One epitope (LASEESAFYVLEHSSFQLLG) was consistently targeted by both acutely (10/12) and remotely (6/7) infected individuals. This epitope was DRB1*1501 restricted, and a major histocompatibility complex peptide tetramer stained PBMCs from acutely infected individuals in the range of 0.003 to 0.042% of CD4(+) T cells. Tetramer-positive populations were initially CD62L(lo); unlike the case for B19-specific CD8(+) T-cell responses, however, CD62L was reexpressed at later times, as responses remained stable or declined slowly. This first identification of B19 CD4(+) T-cell epitopes, including a key immunodominant peptide, provides the tools to investigate the breadth, frequency, and functions of cellular responses to this virus in a range of specific clinical settings and gives an important reference point for analysis of peptide-specific CD4(+) T cells during acute and persistent virus infections of humans. C1 Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England. Karolinska Inst, Div Clin Virol, Stockholm, Sweden. Univ Oxford, John Radcliffe Hosp, Dept Virol, Oxford OX3 9DU, England. Univ Oxford, Nuffield Dept Med, Oxford OX3 9DU, England. RP Kasprowicz, V (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM vkasprowicz@partners.org OI Tolfvenstam, Thomas/0000-0003-3549-8083; bowness, paul/0000-0003-4597-0484 FU Medical Research Council [MC_U137884185]; Wellcome Trust NR 26 TC 10 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2006 VL 80 IS 22 BP 11209 EP 11217 DI 10.1128/JVI.01173-06 PG 9 WC Virology SC Virology GA 102OI UT WOS:000241821300029 PM 16943301 ER PT J AU Yang, XZ Lipchina, I Cocklin, S Chaiken, I Sodroski, J AF Yang, Xinzhen Lipchina, Inna Cocklin, Simon Chaiken, Irwin Sodroski, Joseph TI Antibody binding is a dominant determinant of the efficiency of human immunodeficiency virus type 1 neutralization SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; NONNEUTRALIZING ANTIBODIES; REPLICATION-COMPETENT; MONOCLONAL-ANTIBODIES; HIV-1 VIRIONS; IN-VIVO; GP120; INFECTION; SURFACE; RESISTANCE AB Primary and laboratory-adapted variants of human immunodeficiency virus type 1 (HIV-1) exhibit a wide range of sensitivities to neutralization by antibodies directed against the viral envelope glycoproteins. An antibody directed against an artificial FLAG epitope inserted into the envelope glycoproteins of three HIV-1 isolates with vastly different neutralization sensitivities inhibited all three viruses equivalently. Thus, naturally occurring HIV-1 isolates that are neutralization resistant are not necessarily more impervious to the inhibitory consequences of bound antibody. Moreover, the binding affinity of the anti-FLAG antibody correlated with neutralizing potency, underscoring the dominant impact on neutralization of antibody binding to the envelope glycoproteins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA. RP Yang, XZ (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RE 213A, Boston, MA 02115 USA. EM xyang1@bidmc.harvard.edu FU NIAID NIH HHS [U19 AI067854, R37 AI024755, R01 AI040895, R01 AI039420, AI24755, P30 AI042848, AI064009, R21 AI064009, AI39420, AI40895, AI42848, AI67854, U01 AI067854] NR 44 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2006 VL 80 IS 22 BP 11404 EP 11408 DI 10.1128/JVI.01102-06 PG 5 WC Virology SC Virology GA 102OI UT WOS:000241821300051 PM 16956933 ER PT J AU Dekay, ML Hershey, JC Spranca, MD Ubel, PA Asch, DA AF DeKay, Michael L. Hershey, John C. Spranca, Mark D. Ubel, Peter A. Asch, David A. TI Are medical treatments for individuals and groups like single-play and multiple-play gambles? SO JUDGMENT AND DECISION MAKING JOURNAL LA English DT Article DE aggregation; fungibility; individuals versus groups; medical treatment decisions; multiple-play; repeated-play AB People are often more likely to accept risky monetary gambles with positive expected values when the gambles will be played more than once. We investigated whether this distinction between single-play and multiple-play gambles extends to medical treatments for individual patients and groups of patients. Resident physicians and medical students (n = 69) and undergraduates (n = 99) ranked 9 different flu shots and a no-flu-shot option in 1 of 4 combinations of perspective (individual patient vs. group of 1000 patients) and uncertainty frame (probability vs. frequency). The rank of the no-flu- shot option (a measure of preference for treatment vs. no treatment) was not significantly related to perspective or participant population. The main effect of uncertainty frame and the interaction between perspective and uncertainty frame approached significance (0.1 > p > 0.05), with the no-flu-shot option faring particularly poorly (treatment faring particularly well) when decisions about many patients were based on frequency information. Undergraduate participants believed that the no-flu-shot option would be less attractive (treatment would be more attractive) in decisions about many patients, but these intuitions were inconsistent with the actual ranks. These results and those of other studies suggest that medical treatments for individuals and groups are not analogous to single-play and multiple-play monetary gambles, perhaps because many people are unwilling to aggregate treatment outcomes over patients in the same way that they would compute net gains or losses over monetary gambles. C1 [DeKay, Michael L.] Carnegie Mellon Univ, Dept Engn & Publ Policy, Pittsburgh, PA 15213 USA. [Hershey, John C.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Hershey, John C.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Spranca, Mark D.] ABT Associates Inc, Cambridge, MA 02138 USA. [Ubel, Peter A.] VA Ann Arbor Healthcare Syst, VA Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. [Ubel, Peter A.] Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. [Ubel, Peter A.] Ctr Behav & Decis Sci Med, Ann Arbor, MI USA. [Ubel, Peter A.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Dekay, ML (reprint author), Carnegie Mellon Univ, Dept Engn & Publ Policy, Pittsburgh, PA 15213 USA. EM dekay@andrew.cmu.edu NR 57 TC 5 Z9 6 U1 1 U2 4 PU SOC JUDGMENT & DECISION MAKING PI TALLAHASSEE PA FLORIDA STATE UNIV, TALLAHASSEE, FL 32306-1110 USA SN 1930-2975 J9 JUDGM DECIS MAK JI Judgm. Decis. Mak. PD NOV PY 2006 VL 1 IS 2 BP 134 EP 145 PG 12 WC Psychology, Multidisciplinary SC Psychology GA V54MB UT WOS:000203681700005 ER PT J AU Chen, YW Liu, F Tran, S Zhu, Y Hebert, MJ Ingelfinger, JR Zhang, SL AF Chen, Y-W Liu, F. Tran, S. Zhu, Y. Hebert, M-J Ingelfinger, J. R. Zhang, S-L TI Reactive oxygen species and nuclear factor-kappa B pathway mediate high glucose-induced Pax-2 gene expression in mouse embryonic mesenchymal epithelial cells and kidney explants SO KIDNEY INTERNATIONAL LA English DT Article DE high glucose; Pax-2; ROS; NF-kappa B ID PROXIMAL TUBULAR CELLS; RENAL-COLOBOMA SYNDROME; URETERAL BUD APOPTOSIS; PROTEIN-KINASE-C; OXIDATIVE STRESS; BRANCHING MORPHOGENESIS; DIABETIC COMPLICATIONS; ANGIOTENSINOGEN GENE; SIGNALING PATHWAYS; TRANSGENIC MICE AB Diabetic mellitus confers a major risk of congenital malformations, and is associated with diabetic embryopathy, affecting multiple organs including the kidney. The DNA paired box-2 (Pax-2) gene is essential in nephrogenesis. We investigated whether high glucose alters Pax-2 gene expression and aimed to delineate its underlying mechanism(s) of action using both in vitro (mouse embryonic mesenchymal epithelial cells (MK4) and ex vivo (kidney explant from Hoxb7-green florescent protein (GFP) mice) approaches. Pax-2 gene expression was determined by reverse transcriptase-polymerase chain reaction, Western blotting, and immunofluorescent staining. A fusion gene containing the full-length 50-flanking region of the human Pax-2 promoter linked to a luciferase reporter gene, pGL-2/hPax-2, was transfected into MK4 cells with or without dominant negative I kappa B alpha (DN I kappa B alpha) cotransfection. Fusion gene expression level was quantified by cellular luciferase activity. Reactive oxygen species (ROS) generation was measured by lucigenin assay. Embryonic kidneys from Hoxb7-GFP mice were cultured ex vivo. High D(+) glucose (25 mM), compared to normal glucose (5 mM), specifically induced Pax-2 gene expression in MK4 cells and kidney explants. High glucose-induced Pax-2 gene expression is mediated, at least in part, via ROS generation and activation of the nuclear factor kappa B signaling pathway, but not via protein kinase C, p38 mitogen-activated protein kinase (MAPK), and p44/42 MAPK signaling. C1 Univ Montreal, CHU Montreal, Hotel Dieu, Montreal, PQ H2W 1T7, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02115 USA. RP Zhang, SL (reprint author), Univ Montreal, CHU Montreal, Hotel Dieu, Pavillon Masson,3850 Rue St Urbain, Montreal, PQ H2W 1T7, Canada. EM shao.ling.zhang@umontreal.ca NR 54 TC 12 Z9 12 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2006 VL 70 IS 9 BP 1607 EP 1615 DI 10.1038/sj.ki.5001871 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 100KH UT WOS:000241667200019 PM 16985513 ER PT J AU Rakowski, SK Winterkorn, EB Paul, E Steele, DJR Halpern, EF Thiele, EA AF Rakowski, S. K. Winterkorn, E. B. Paul, E. Steele, D. J. R. Halpern, E. F. Thiele, E. A. TI Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors SO KIDNEY INTERNATIONAL LA English DT Article DE tuberous sclerosis complex; angiomyolipoma; cysts; renal cell carcinoma; lymphangioleiomyomatosis ID CELL CARCINOMA; MUTATIONAL ANALYSIS; TSC2; LYMPHANGIOLEIOMYOMATOSIS; KIDNEY; DISEASE; ANGIOMYOLIPOMA; INVOLVEMENT; MIGRATION; CHILDREN AB Tuberous sclerosis complex is a genetic disorder characterized by hamartomatous lesions in multiple organs, frequently involving the kidney. We conducted a retrospective review of the clinical and radiographic records of 167 patients with tuberous sclerosis to determine the frequency of renal disease, the likelihood of significant renal morbidity, and the effects of genotype (TSC1 vs TSC2) and gender on renal phenotype. Renal lesions were seen in 57.5% of patients. Of these, angiomyolipoma (AML) occurred in 85.4%, cysts in 44.8%, and renal cell carcinoma in 4.2%. Both AML and cysts were significantly more common and more numerous in TSC2 than in TSC1. AML was significantly more common in female than in male patients, but cysts showed no correlation with gender. Eleven patients developed renal abnormalities during their care in this practice at an average age of onset of 11.3 years (range 3.8-23 years). The frequency and number of renal lesions were positively correlated with age. Interventions, including arterial embolization and nephrectomy, were performed in 11 (6.6%) patients. Among female patients with lymphangioleiomyomatosis, renal AML was universally present. Our findings confirm a high rate of renal involvement; a low rate of serious complications; significant associations between renal involvement, genotype, and gender; and a significant association between renal and pulmonary involvement in female patients. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Nephrol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Herscot Ctr Tuberous Sclerosis Complex, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 29 TC 154 Z9 165 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2006 VL 70 IS 10 BP 1777 EP 1782 DI 10.1038/sj.ki.5001853 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 104DO UT WOS:000241936500018 PM 17003820 ER PT J AU Melanson, S Flood, J Lewandrowski, K AF Melanson, Stacy Flood, James Lewandrowski, Kent TI Add-on testing in the clinical laboratory: Observations from two large academic medical centers SO LABMEDICINE LA English DT Article ID AUTOMATION AB Add-on testing is an inefficient process that occurs frequently in clinical laboratories; however, describing add-on testing and its effects on laboratory operations continues to be sparse. We compare 1 week of add-on testing in the clinical chemistry laboratory of 2 large academic medical centers, Massachusetts General Hospital and Brigham and Womens Hospital. A detailed examination of add-on testing at each institution reveals many common features including frequency of add-ons, test distribution, and average number of tests requested, suggesting that our observations may be extrapolated to other academic medical centers. Process improvements such as automation, order communication, alteration of order entry screens, and expansion of test panels may reduce add-on testing. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Melanson, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD NOV PY 2006 VL 37 IS 11 BP 675 EP 678 DI 10.1309/BT8WH8M27YFETE9P PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 099YA UT WOS:000241632500015 ER PT J AU Weaver, FM Stern, MB Follett, K AF Weaver, Frances M. Stern, Matthew B. Follett, Kenneth TI Deep-brain stimulation in Parkinson's disease SO LANCET NEUROLOGY LA English DT Editorial Material C1 Hines VA Med Ctr, Mid W Ctr Hlth Serv & Policy Res, Hines, IL USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Penn Hlth Syst, Philadelphia, PA USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Nebraska Med Ctr, Omaha, NE 68198 USA. RP Weaver, FM (reprint author), Hines VA Med Ctr, Mid W Ctr Hlth Serv & Policy Res, Hines, IL USA. EM frances.weaver@va.gov NR 5 TC 4 Z9 4 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2006 VL 5 IS 11 BP 900 EP 901 DI 10.1016/S1474-4422(06)70586-5 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 099JY UT WOS:000241591600005 PM 17052655 ER PT J AU Elbaz, A Nelson, LM Payami, H Ioannidis, JPA Fiske, BK Annesi, G Belin, AC Factor, SA Ferrarese, C Hadjigeorgiou, GM Higgins, DS Kawakami, H Kruger, R Marder, KS Mayeux, RP Mellick, GD Nutt, JG Ritz, B Samii, A Tanner, CM Van Broeckhoven, C Van Den Eeden, SK Wirdefeldt, K Zabetian, CP Dehem, M Montimurro, JS Southwick, A Myers, RM Trikalinos, TA AF Elbaz, Alexis Nelson, Lorene M. Payami, Haydeh Ioannidis, John P. A. Fiske, Brian K. Annesi, Grazia Belin, Andrea Carmine Factor, Stewart A. Ferrarese, Carlo Hadjigeorgiou, Georgios M. Higgins, Donald S. Kawakami, Hideshi Krueger, Rejko Marder, Karen S. Mayeux, Richard P. Mellick, George D. Nutt, John G. Ritz, Beate Samii, Ali Tanner, Caroline M. Van Broeckhoven, Christine Van Den Eeden, Stephen K. Wirdefeldt, Karin Zabetian, Cyrus P. Dehem, Marie Montimurro, Jennifer S. Southwick, Audrey Myers, Richard M. Trikalinos, Thomas A. TI Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease: a large-scale international study SO LANCET NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; COMMON GENETIC VARIANT; RISK; SEMA5A AB Background A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson's disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. Methods Investigators from three Michael J Fox Foundation for Parkinson's Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson's disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. Findings In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0(.)89 to 1(.)09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0(.)95 to 1.08); there was little heterogeneity except for SNP rs7520966. Interpretation Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson's disease. C1 J Fox Fdn Parkinsons Res, New York, NY 10163 USA. INSERM, Unit 708, F-75654 Paris 13, France. Stanford Univ, Med Ctr, Sch Med, Dept Hlth Res & Policy,Div Epidemiol, Stanford, CA 94305 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12237 USA. Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. CNR, Inst Neurol Sci, Mangone, Italy. Karolinska Inst, Dept Neurosci, S-10401 Stockholm, Sweden. Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Univ Milan, Osped San Gerardo, Dept Neurosci, Neurol Sect, I-20122 Milan, Italy. Univ Thessaly, Sch Med, Larisa, Greece. Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Epidemiol, Hiroshima 730, Japan. Univ Tubingen, Ctr Neurol, D-72074 Tubingen, Germany. Univ Tubingen, Hertie Inst Clin Brain Res, D-72074 Tubingen, Germany. Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. Griffith Univ, Eskitis Inst Cell & Mol Therapies, Nathan, Qld 4111, Australia. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. VA Puget Sound Healthcare Syst, Parkinson Dis Res Educ & Clin Ctr, Seattle, WA USA. Parkinsons Inst, Sunnyvale, CA USA. Univ Antwerp VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, B-2610 Antwerp, Belgium. Kaiser Fdn, Res Inst, Div Res, Oakland, CA USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. VA Puget Sound Hlth Care Syst, Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Genoscreen, Lille, France. Stanford Univ, Med Ctr, Sch Med, Dept Genet, Stanford, CA 94305 USA. RP Fiske, BK (reprint author), J Fox Fdn Parkinsons Res, Grand Cent Stn,POB 4777, New York, NY 10163 USA. EM bfiske@michaeljfox.org RI Trikalinos, Thomas/A-1217-2009; Kawakami, Hideshi/A-2086-2009; Nelson, Lorene/D-1305-2011; Ioannidis, John/G-9836-2011; Nuytemans, Karen/F-4797-2012; Morino, Hiroyuki/H-9583-2013; Mellick, George/A-7650-2010; Ritz, Beate/E-3043-2015; OI Goldwurm, Stefano/0000-0002-1651-567X; Kawakami, Hideshi/0000-0002-1405-0901; Morino, Hiroyuki/0000-0002-5190-3547; Mellick, George/0000-0002-7211-4651; Zabetian, Cyrus/0000-0002-7739-4306; Elbaz, Alexis/0000-0001-9724-5490 FU NIA NIH HHS [AG 08017, P30 AG008017, U24 AG021886]; NIEHS NIH HHS [P01 ES016732, ES10758, R01 ES010544, R01 ES010758]; NINDS NIH HHS [K08 NS044138, K08-NS044138, NS R01-31964, NS R01-36960] NR 25 TC 68 Z9 70 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2006 VL 5 IS 11 BP 917 EP 923 DI 10.1016/S1474-4422(06)70579-8 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 099JY UT WOS:000241591600014 PM 17052658 ER PT J AU Francis, DO Kaufman, R Yueh, B Mock, C Nathens, AB AF Francis, David O. Kaufman, Robert Yueh, Bevan Mock, Charlie Nathens, Avery B. TI Air bag-induced orbital blow-out fractures SO LARYNGOSCOPE LA English DT Article DE orbital; blow-out fracture; air bags; motor vehicle crashes; out-of-position; facial trauma; CIREN ID FRONTAL AUTOMOBILE CRASHES; MOTOR-VEHICLE COLLISIONS; EYE INJURIES; FLOOR FRACTURES; MECHANISM; PATTERNS; AIRBAGS AB Rationale. Although air bags have decreased the risk of serious injury from motor vehicle crashes, their deployment is not innocuous and can result in injury. The force of the deploying air bag can cause orbital blow-out fractures. We investigated the circumstances that predispose a crash occupant to this particular injury. Study Design: The authors conducted a case series. Methods: A total of 150 orbital fractures occurred among 2,739 occupants in crashes included in the Crash Injury Research and Engineering Network (CIREN) database from January 1997 to July 2005. Ten orbital blow-out fractures attributed solely to air bag deployment were extracted and four reported in depth. Occupant, vehicle, and crash char acteristics were reviewed for predisposing similarities and to investigate the mechanism of injury. Results: All crashes had air bag deployment and a frontal or near-frontal principle direction of force. Nine of 10 injured occupants were positioned within the air bag's deployment zone at the time of impact as a result of a forward seat track position, falling asleep at the wheel, being unestrained, or having decelerated before impact. Six of 10 occupants experiencing orbital blow-out fractures were of shorter than average height. Based on rigorous crash reconstructions, the orbital blow-out injuries were felt to be causally related to air bag deployment. Conclusion: Air bag deployment may result in orbital blow-out fractures. Occupants positioned in close proximity to the air bag during its deployment phase appear to be at increased risk for orbital blow-out fractures. C1 Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Harborview Injury Prevent & Res Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Hlth Serv Res & Dev Serv, Seattle, WA USA. RP Nathens, AB (reprint author), 325 9th Ave,Box 359796, Seattle, WA 98104 USA. EM anathens@u.washington.edu OI Mock, Charles/0000-0002-0564-568X; Yueh, Bevan/0000-0003-1380-1053 NR 40 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2006 VL 116 IS 11 BP 1966 EP 1972 DI 10.1097/01.mlg.0000236080.63733.eb PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 102JG UT WOS:000241806300006 PM 17075425 ER PT J AU Vidal-Gonzalez, I Vidal-Gonzalez, B Rauch, SL Quirk, GJ AF Vidal-Gonzalez, Ivan Vidal-Gonzalez, Benjamin Rauch, Scott L. Quirk, Gregory J. TI Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear SO LEARNING & MEMORY LA English DT Article ID MEDIAL PREFRONTAL CORTEX; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; INTRA-AMYGDALOID PROJECTIONS; BASOLATERAL AMYGDALA; CORTICAL PROJECTIONS; EFFERENT PROJECTIONS; ELECTROLYTIC LESIONS; PERIAQUEDUCTAL GRAY; SYNAPTIC PLASTICITY; LATERAL NUCLEUS AB Recent studies using lesion, infusion, and unit-recording techniques suggest that the infralimbic (IL) subregion of medial prefrontal cortex (mPFC) is necessary for the inhibition of conditioned fear following extinction. Brief microstimulation of IL paired with conditioned tones, designed to mimic neuronal tone responses, reduces the expression of conditioned fear to the tone. In the present study we used microstimulation to investigate the role of additional mPFC subregions: the prelimbic (PL), dorsal anterior cingulate (ACd), and medial precentral (PrCm) cortices in the expression and extinction of conditioned fear. These are tone-responsive areas that have been implicated in both acquisition and extinction of conditioned fear. In contrast to IL, microstimulation of PL increased the expression of conditioned fear and prevented extinction. Microstimulation of ACd and PrCm had no effect. Under low-footshock conditions (to avoid ceiling levels of freezing), microstimulation of PL and IL had opposite effects, respectively increasing and decreasing freezing to the conditioned tone. We suggest that PL excites amygdala output and IL inhibits amygdala output, providing a mechanism for bidirectional modulation of fear expression. C1 Ponce Sch Med, Dept Physiol, Ponce, PR 00732 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Quirk, GJ (reprint author), Ponce Sch Med, Dept Physiol, Ponce, PR 00732 USA. EM gjquirk@yahoo.com FU NIGMS NIH HHS [S06 GM008239, GM008239]; NIMH NIH HHS [MH058883, MH072156, R01 MH058883, R21 MH072156, R29 MH058883, R37 MH058883] NR 63 TC 288 Z9 292 U1 0 U2 18 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD NOV-DEC PY 2006 VL 13 IS 6 BP 728 EP 733 DI 10.1101/lm.306106 PG 6 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 111WE UT WOS:000242485600008 PM 17142302 ER PT J AU Palomero, T McKenna, K O-Neil, J Galinsky, I Stone, R Suzukawa, K Stiakaki, E Kalmanti, M Fox, EA Caligiuri, MA Aster, JC Look, AT Ferrando, AA AF Palomero, T. McKenna, K. O-Neil, J. Galinsky, I. Stone, R. Suzukawa, K. Stiakaki, E. Kalmanti, M. Fox, E. A. Caligiuri, M. A. Aster, J. C. Look, A. T. Ferrando, A. A. TI Activating mutations in NOTCH1 in acute myeloid leukemia and lineage switch leukemias SO LEUKEMIA LA English DT Article DE NOTCH1; AML; leukemia stem cells ID HEMATOPOIETIC PROGENITOR CELLS; INHIBITS DIFFERENTIATION; EXPRESSION; ML-2 AB Activating mutations in NOTCH1 are found in over 50% of human T-cell lymphoblastic leukemias (T-ALLs). Here, we report the analysis for activating NOTCH1 mutations in a large number of acute myeloid leukemia (AML) primary samples and cell lines. We found activating mutations in NOTCH1 in a single M0 primary AML sample, in three (ML1, ML2 and CTV-1) out of 23 AML cell lines and in the diagnostic ( myeloid) and relapsed ( T-lymphoid) clones in a patient with lineage switch leukemia. Importantly, the ML1 and ML2 AML cell lines are derived from an AML relapse in a patient initially diagnosed with T-ALL. Overall, these results demonstrate that activating mutations in NOTCH1 are mostly restricted to T-ALL and are rare in AMLs. The presence of NOTCH1 mutations in myeloid and T-lymphoid clones in lineage switch leukemias establishes the common clonal origin of the diagnostic and relapse blast populations and suggests a stem cell origin of NOTCH1 mutations during the molecular pathogenesis of these tumors. C1 Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. Columbia Univ, Med Ctr, Dept Pathol, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tsukuba, Clin & Expt Hematol Dept, Grad Sch Comprehens Human Sci, Ibaraki, Japan. Univ Crete, Dept Pediat Hematol Oncol, Iraklion, Greece. Harvard Univ, Mol Diagnost Lab, Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Internal Med Hematol Oncol Dept, Ctr Comprehens Canc, Columbus, OH 43210 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Columbia Univ, Med Ctr, Dept Pediat, New York, NY USA. RP Ferrando, AA (reprint author), Columbia Univ, Inst Canc Genet, 1130 St Nicholas Ave,Room 901B, New York, NY 10032 USA. EM af2196@columbia.edu RI Ferrando, Adolfo /Q-7026-2016; OI Suzukawa, Kazumi/0000-0001-9904-3905 FU NCI NIH HHS [CA68484, CA109901] NR 19 TC 36 Z9 39 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2006 VL 20 IS 11 BP 1963 EP 1966 DI 10.1038/sj.leu.2404409 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 098XJ UT WOS:000241556100008 PM 17008890 ER PT J AU Schittenhelm, MM Yee, KWH Tyner, JW McGreevey, L Haley, AD Town, A Griffith, DJ Bainbridge, T Braziel, RM O'Farrell, AM Cherrington, JM Heinrich, MC AF Schittenhelm, M. M. Yee, K. W. H. Tyner, J. W. McGreevey, L. Haley, A. D. Town, A. Griffith, D. J. Bainbridge, T. Braziel, R. M. O'Farrell, A. -M. Cherrington, J. M. Heinrich, M. C. TI FLT3 K663Q is a novel AML-associated oncogenic kinase: determination of biochemical properties and sensitivity to Sunitinib (SU11248) SO LEUKEMIA LA English DT Article DE AML; FLT3; mutations; tyrosine kinase; growth factor receptor ID ACUTE MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; INTERNAL TANDEM DUPLICATION; RECEPTOR TYROSINE KINASE; WILD-TYPE; C-KIT; CONSTITUTIVE ACTIVATION; NORMAL CYTOGENETICS; POOR-PROGNOSIS; 32D CELLS AB Somatic mutations of FLT3 resulting in constitutive kinase activation are the most common acquired genomic abnormality found in acute myeloid leukemia (AML). The majority of these mutations are internal tandem duplications (ITD) of the juxtamembrane region (JM). In addition, a minority of cases of AML are associated with mutation of the FLT3 activation loop (AL), typically involving codons D835 and/or I836. We hypothesized that other novel mutations of FLT3 could also contribute to leukemogenesis. We genotyped 109 cases of AML and identified two novel gain-of-function mutations. The first mutation, N841H, is similar to previously described mutations involving amino-acid substitutions of codon 841. The other novel mutation, FLT3 K663Q, is the first AML-associated gain-of-function mutation located outside the JM and AL domains. Of note, this mutation was potently inhibited by Sunitinib (SU11248), a previously described FLT3 kinase inhibitor. Sunitinib reduced the proliferation and induced apoptosis of transformed Ba/F3 cells expressing FLT3 K663Q. The potency of Sunitinib against FLT3 K663Q was similar to its potency against FLT3 ITD mutations. We conclude that FLT3 mutations in AML can involve novel regions of the TK1. Future studies are needed to define the incidence and prognostic significance of FLT3 mutations outside the well-established JM and AL regions. C1 Oregon Hlth Sci Univ, Dept Pathol & Med, Inst Canc, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Tubingen, Med Ctr, Dept Hematol Oncol Rheumatol Immunol & Pneumol, Tubingen, Germany. SUGEN Inc, Dept Preclin Res & Exploratory Med, San Francisco, CA USA. RP Heinrich, MC (reprint author), Oregon Hlth Sci Univ, Inst Canc, Div Hematol & Med Oncol, Dept Med, 3710 SW US Vet Hosp Rd,R&D-19, Portland, OR 97239 USA. EM heinrich@ohsu.edu OI Tyner, Jeffrey/0000-0002-2133-0960 FU NCI NIH HHS [P30 CA69533, 5-T32-CA101690-03] NR 41 TC 25 Z9 25 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2006 VL 20 IS 11 BP 2008 EP 2014 DI 10.1038/sj.leu.2404374 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 098XJ UT WOS:000241556100014 PM 16990784 ER PT J AU Ioannou, GN AF Ioannou, George N. TI Development and validation of a model predicting graft survival after liver transplantation SO LIVER TRANSPLANTATION LA English DT Article ID BODY-MASS INDEX; DONOR LIVER; PRIMARY NONFUNCTION; UNITED-STATES; RISK-FACTORS; RECIPIENTS; MORTALITY; HEPATITIS; IMPACT; ALLOGRAFTS AB This study aimed to develop and validate a comprehensive model that predicts survival after liver transplantation based on pretransplant donor and recipient characteristics. Complete data were available from the United Network for Organ Sharing for 20,301 persons who underwent liver transplantation in the United States between 1994 and 2003. Proportional-hazards regression was used to identify the donor and recipient characteristics that best predicted survival and incorporate these characteristics in a multivariate model. A data-splitting approach was used to compare survival predicted by the model to the observed survival in samples not used in the derivation of the model. A model was derived using 4 donor characteristics (age, cold ischemia time, gender, and race/ethnicity) and 9 recipient characteristics (age, body mass index, model for end-stage liver disease score, United Network for Organ Sharing priority status, gender, race/ethnicity, diabetes mellitus, cause of liver disease, and serum albumin) that adequately predicted survival after liver transplantation in patients without hepatitis C virus, and a slightly different model was used for patients with hepatitis C virus. The models illustrate that variations in both pretransplant donor and recipient characteristics have a large effect on posttransplant survival. In conclusion, the models presented here can be used to derive scores that are proportional to the excess risk of graft loss after liver transplantation for potential donors, recipients, or donor/recipient combinations. The models may be used to inform liver transplant candidates and their doctors what posttransplant survival would be expected when a given donor is offered and may be particularly helpful for marginal or high-risk donors. C1 Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA. Hlth Serv Res & Dev, Div Gastroenterol, Dept Med, Hepatitis C Resource Ctr, Seattle, WA USA. Univ Washington, Div Gastroenterol, Dept Med, Seattle, WA USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU PHS HHS [231-00-0115] NR 33 TC 71 Z9 72 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2006 VL 12 IS 11 BP 1594 EP 1606 DI 10.1002/lt.20764 PG 13 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 099JS UT WOS:000241590700006 PM 16952176 ER PT J AU van der Kouwe, AJW Benner, T Dale, AM AF van der Kouwe, Andre J. W. Benner, Thomas Dale, Anders M. TI Real-time rigid body motion correction and shimming using cloverleaf navigators SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE motion correction; shim correction; real-time correction; brain imaging; clover leaf navigator ID MAGNETIC-RESONANCE; PROPELLER MRI; BRAIN IMAGES; HEAD MOTION; REGISTRATION; ECHOES; OPTIMIZATION; ROBUST; FMRI AB Subject motion during scanning can greatly reduce MRI image quality and is a major reason for discarding data in both clinical and research scanning. The quality of the high-resolution structural data used for morphometric analysis is especially compromised by subject movement because high-resolution scans are of longer duration. A method is presented that measures and corrects rigid body motion and associated first-order shim changes in real time, using a pulse sequence with embedded cloverleaf navigators and a feedback control mechanism. The procedure requires a 12-s preliminary mapping scan. A singlepath, 4.2-ms cloverleaf navigator is inserted every repetition time (TR) after the readout of a 313 fast low-angle shot (FLASH) sequence, requiring no additional RF pulses and minimally impacting scan duration. Every TR, a rigid body motion estimate is made and a correction is fed back to adjust the gradients and shim offsets. Images are corrected and reconstructed on the scanner computer for immediate access. Correction for between-scan motion can be accomplished by using the same reference map for each scan repetition. Human and phantom tests demonstrated a consistent improvement in image quality if motion occurred during the acquisition. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. RP van der Kouwe, AJW (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM andre@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41RR14075, U24RR021382]; NIBIB NIH HHS [R01EB00790, R01EB1550, R21EB02530]; NINDS NIH HHS [5P01NS035611] NR 24 TC 90 Z9 91 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2006 VL 56 IS 5 BP 1019 EP 1032 DI 10.1002/mrm.21038 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 101SX UT WOS:000241761900011 PM 17029223 ER PT J AU Setsompop, K Wald, LL Alagappan, V Gagoski, B Hebrank, F Fontius, U Schmitt, F Adalsteinsson, E AF Setsompop, Kawin Wald, Lawrence L. Alagappan, Vijayanand Gagoski, Borjan Hebrank, Franz Fontius, Ulrich Schmitt, Franz Adalsteinsson, Elfar TI Parallel RF transmission with eight channels at 3 Tesla SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel excitation; RF acceleration; RIF coil array; RIF inhomogeneity; RF design ID EXCITATION; PULSE AB Spatially selective RF waveforms were designed and demonstrated for parallel excitation with a dedicated eight-coil transmit array on a modified 3T human MRI scanner. Measured excitation profiles of individual coils in the array were used in a low-flip-angle pulse design to achieve desired spatial target profiles with two- (2D) and three-dimensional (3D) k-space excitation with simultaneous transmission of RF on eight channels. The 2D pulse excited a high-resolution spatial pattern in-plane, while the 3D trajectory produced high-quality slice selection with a uniform in-plane excitation despite the highly nonuniform individual spatial profiles of the coil array. The multichannel parallel RF excitation was used to accelerate the 2D excitation by factors of 2-8, and experimental results were in excellent agreement with simulations based on the measured coil maps. Parallel RF transmission may become critical for robust and routine human studies at very high field strengths where B, inhomogeneity is commonly severe. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Siemens Med Solut, Charlestown, MA USA. Siemens Med Solut, Erlangen, Germany. RP Setsompop, K (reprint author), Bldg 26,Room 353,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM kawin@mit.edu RI Adalsteinsson, Elfar/F-2477-2010; Setsompop, Kawin/P-1464-2014; Wald, Lawrence/D-4151-2009 OI Setsompop, Kawin/0000-0003-0455-7634; FU NCRR NIH HHS [P41RR14075] NR 19 TC 93 Z9 93 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2006 VL 56 IS 5 BP 1163 EP 1171 DI 10.1002/mrm.21042 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 101SX UT WOS:000241761900030 PM 17036289 ER PT J AU Carvalho, FD Medina-Flores, R Sartori, AL Wiley, CA AF Carvalho, F. D. Medina-Flores, R. Sartori, A. L. Wiley, C. A. TI YKL-40, a potential inhibitor of axonal growth and pathfinding SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Div Neuropathol, Pittsburgh, PA 15213 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 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S93 EP S93 DI 10.1016/j.matbio.2006.08.256 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600255 ER PT J AU Inada, M Byrne, MH Yu, M Hirose, K Miyaura, C Lopez-Otin, C Shapiro, SD Krane, SM AF Inada, M. Byrne, M. H. Yu, M. Hirose, K. Miyaura, C. Lopez-Otin, C. Shapiro, S. D. Krane, S. M. TI Collagenases in skeletal development and remodeling SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Tokyo Univ Agr & Technol, Koganei, Tokyo 1848588, Japan. Univ Oviedo, Oviedo 33006, Spain. RI inada, masaki/D-1581-2013 OI inada, masaki/0000-0002-5066-8506 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S49 EP S50 DI 10.1016/j.matbio.2006.08.137 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600136 ER PT J AU Maxfield, AB Hucthagowder, V Gitlin, JD Joseph, EM Urban, Z AF Maxfield, A. B. Hucthagowder, V. Gitlin, J. D. Joseph, E. M. Urban, Z. TI Fibulin-4 function in zebrafish SO MATRIX BIOLOGY LA English DT Meeting Abstract CT Biennial Meeting of the American-Society-for-Matrix-Biology CY NOV 01-04, 2006 CL Nashville, TN SP Amer Soc Matrix Biol C1 Univ Washington, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Univ Washington, Sch Med, Dept Genet, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RI Urban, Zsolt/B-1977-2008; Hucthagowder, Vishwanathan/C-9831-2009; Urban, Zsolt/A-2018-2013 OI Urban, Zsolt/0000-0003-3890-1843 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 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 2006 VL 25 SU S BP S20 EP S21 DI 10.1016/j.matbio.2006.08.058 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103CP UT WOS:000241863600057 ER PT J AU Parvizi, J Arciniegas, DB Bernardini, GL Hoffmann, MW Mohr, JP Rapoport, MJ Schmahmann, JD Silver, JM Tuhrim, S AF Parvizi, Josef Arciniegas, David B. Bernardini, Gary L. Hoffmann, Michael W. Mohr, Jay P. Rapoport, Mark J. Schmahmann, Jeremy D. Silver, Jonathan M. Tuhrim, Stanley TI Diagnosis and management of pathological laughter and crying SO MAYO CLINIC PROCEEDINGS LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN-INJURY; PSEUDOBULBAR AFFECT; MULTIPLE-SCLEROSIS; EMOTIONAL LABILITY; STROKE; PREVALENCE; DEXTROMETHORPHAN/QUINIDINE; CITALOPRAM; VALIDATION AB Patients with various neurologic disorders exhibit exaggerated or inappropriate episodes of laughter, crying, or both without an apparent motivating stimulus or in response to stimuli that would not have elicited such an emotional response before the onset of the underlying disease. During these episodes, patients have difficulty controlling their emotional expression according to the contextual information. In contrast, patients with mood disorders have a pervasive and sustained change in their emotional experience and thus exhibit spells of laughter or crying because of an underlying mania or depression. This article focuses on the clinical presentation, diagnosis, prevalence, and proposed pathophymological mechanisms of and available treatment options for this clinical phenomenon. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Albany Med Ctr, Albany, NY USA. Univ S Florida, Tampa, FL USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NYU, Sch Med, New York, NY USA. Mt Sinai Med Ctr, New York, NY 10029 USA. RP Parvizi, J (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Pl, Los Angeles, CA 90095 USA. EM jparvizi@ucla.edu RI Arciniegas, David/A-3792-2009 NR 31 TC 28 Z9 28 U1 0 U2 5 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD NOV PY 2006 VL 81 IS 11 BP 1482 EP 1486 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 101SN UT WOS:000241760900012 PM 17120404 ER PT J AU Chaudhuri, AR de Waal, EM Pierce, A Van Remmen, H Ward, WE Richardson, A AF Chaudhuri, Asish R. de Waal, Eric M. Pierce, Anson Van Remmen, Holly Ward, Walter E. Richardson, Arlan TI Detection of protein carbonyls in aging liver tissue: A fluorescence-based proteornic approach SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE protein oxidation; protein carbonyls; fluorescence; proteomics; aging ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; OXIDATIVELY MODIFIED PROTEINS; METAL-CATALYZED OXIDATION; AMINO-ACID-RESIDUES; OXIDIZED PROTEINS; IMMUNOCHEMICAL DETECTION; SUPEROXIDE-DISMUTASE; POLYACRYLAMIDE GELS; ALZHEIMERS-DISEASE; PROTEOMIC ANALYSIS AB Protein carbonyls are commonly used as a marker of protein oxidation in cells and tissues. Currently, 2,4-dinitrophenyl hydrazine (DNPH) is widely used (spectrophotometrically or immunologically) to quantify the global carbonyl levels in proteins and identify the specific proteins that are carbonylated. We have adapted a fluorescence-based approach using fluorescein-5-thiosemicarbazide (FTC), to quantify the global protein carbonyls as well as the carbonyl levels on individual proteins in the proteome. Protein carbonyls generated in vitro were quantified by labeling the oxidized proteins with FTC followed by separating the FTC-labeled protein from free probe by gel electrophoresis. The reaction of FTC with protein carbonyls was found to be specific for carbonyl groups. We measured protein carbonyl levels in the livers of young and old mice, and found a significant increase (two-fold) in the global protein carbonyl levels with age. Using 2-D gel electrophoresis, we used this assay to directly measure the chances in protein carbonyl levels in specific proteins. We identified 12 proteins showing a greater than two-fold increase in carbonyl content (pmoles of carbonyls/mu g of protein) with age. Most of the 12 proteins contained transition metal binding sites, with Cu/Zn superoxide dismutase containing the highest molar ratio of carbonyls in old mice. Thus, the fluorescence-based assay gives investigators the ability to identify potential target proteins that become oxidized under different pathological and physiological conditions. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu RI Pierce, Anson/D-1079-2012 OI Pierce, Anson/0000-0002-1383-0180 FU NIA NIH HHS [P01 AG020591, P01 AG19316, R01 AG025362] NR 71 TC 91 Z9 93 U1 3 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV PY 2006 VL 127 IS 11 BP 849 EP 861 DI 10.1016/j.mad.2006.08.006 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 105RF UT WOS:000242049300005 PM 17002888 ER PT J AU Iwabuchi, T Goetinck, PF AF Iwabuchi, Tokuro Goetinck, Paul F. TI Syndecan-4 dependent FGF stimulation of mouse vibrissae growth SO MECHANISMS OF DEVELOPMENT LA English DT Article DE FGF signaling; syndecan-4; growth; regeneration; mouse vibrissae ID HAIR FOLLICLE MORPHOGENESIS; HEPARAN-SULFATE PROTEOGLYCANS; FIBROBLAST-GROWTH; CYTOPLASMIC DOMAIN; CELL-DIFFERENTIATION; FEATHER DEVELOPMENT; DERMAL PAPILLA; SONIC-HEDGEHOG; PDZ PROTEIN; ROOT SHEATH AB The development, maintenance and regeneration of epithelial appendages such as hairs or vibrissae depend on reciprocal interactions between the epidermal and the dermal components of the integument. Growth factors are among a number of signaling molecules that have been identified during these developmental events. Growth factors such as fibroblast growth factors (FGFs) bind cell surface heparan sulfate proteoglycans (HSPGs) on their heparan sulfate side chains and as such these proteoglycans act as co-receptors for FGF receptors (FGFRs) by forming a ternary signaling complex of HSPG, FGFR and FGF. The syndecans make up a family (syndecan-1-4) of transmembrane HSPGs. In the present study we examined the growth response of mouse vibrissae to HSPG-binding growth factors as a function of the presence or absence of syndecan-4 in an organ culture system. Syndecan-4 is expressed on keratinocytes that make up the inner root sheath of the vibrissa. Vibrissae from wild-type mice, but not from syndecan-4 null mice, displayed a statistically significant and dose-dependent growth response to FGF-1, FGF-2 and FGF-7. In contrast, a statistically significant growth response is seen in vibrissae from both wild-type and syndecan-4 null mice when the culture medium is supplemented with either hepatocyte growth factor (HGF) that binds to HSPG, insulin that does not bind to HSPG or 5% fetal bovine serum. The syndecan-4 dependent effect of FGF-1, -2 and -7 on the transcriptional activity of IRS expressed genes and of genes involved in cell proliferation reveals a number of different response patterns. In vivo, the vibrissae of syndecan-4 null mice are shorter and have a smaller diameter than those of wild-type mice and this phenotype may result from a suboptimal response to growth factors. Syndecan-1, which is expressed in the outer root sheath of the vibrissae shaft, does not influence the response of the vibrissae to FGF-1, -2 and -7 and the length and diameter of vibrissae of syndecan-1 null mice do not differ from those of wild-type mice. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Goetinck, PF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM paul.goetinck@cbrc2.mgh.harvard.edu FU NICHD NIH HHS [HD-37490] NR 61 TC 11 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD NOV PY 2006 VL 123 IS 11 BP 831 EP 841 DI 10.1016/j.mod.2006.08.003 PG 11 WC Developmental Biology SC Developmental Biology GA 116FA UT WOS:000242786700004 PM 16989989 ER PT J AU Schackman, BR Gebo, KA Walensky, RP Losina, E Muccio, T Sax, PE Weinstein, MC Seage, GR Moore, RD Freedberg, KA AF Schackman, Bruce R. Gebo, Kelly A. Walensky, Rochelle P. Losina, Elena Muccio, Tammy Sax, Paul E. Weinstein, Milton C. Seage, George R., III Moore, Richard D. Freedberg, Kenneth A. TI The lifetime cost of current human immunodeficiency virus care in the United States SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 3rd International-AIDS-Society Conference on HIV Pathogenesis and Treatment CY JUL 24-27, 2005 CL Rio de Janeiro, BRAZIL SP Int AIDS Soc DE HIV; AIDS; cost; life expectancy; computer simulation model ID ACTIVE ANTIRETROVIRAL THERAPY; MYCOBACTERIUM-AVIUM COMPLEX; HIV-INFECTED PATIENTS; CD4 CELL COUNTS; OPPORTUNISTIC INFECTIONS; FUSION INHIBITOR; CONTROLLED-TRIAL; MEDICAL-CARE; PROPHYLAXIS; COMBINATION AB Objective: We sought to project the lifetime cost of medical care for human immunodefiency virus (HIV)-infected adults using current antiretroviral therapy (ART) standards. Methods: Medical visits and hospitalizations for any reason were from the HIV Research Network, a consortium of high-volume HIV primary care sites. HIV treatment drug regimen efficacies were from clinical guidelines and published sources; data on other drugs used were not available. In a computer simulation model, we projected HIV medical care costs in 2004 U.S. dollars. Results: From the time of entering HIV care, per person projected life expectancy is 24.2 years, discounted lifetime cost is $385,200, and undiscounted cost is $618,900 for adults who initiate ART with CD4 cell count < 350/mu L. Seventy-three percent of the cost is antiretroviral medications, 13% inpatient care, 9% outpatient care, and 5% other HIV-related medications and laboratory costs. For patients who initiate ART with CD4 cell count < 200/mu L, projected life expectancy is 22.5 years, discounted lifetime cost is $354,100 and undiscounted cost is $567,000. Results are sensitive to drug manufacturers' discounts, ART efficacy, and use of enfavirtide for salvage. If costs are discounted to the time of infection, the discounted lifetime cost is $303,100. Conclusions: Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S. C1 Cornell Univ, Dept Publ Hlth, Weill Med Coll, New York, NY 10021 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Schackman, BR (reprint author), Cornell Univ, Dept Publ Hlth, Weill Med Coll, 411 E 69th St, New York, NY 10021 USA. EM brs2006@med.cornell.edu RI Gebo, Kelly/B-9223-2009 FU NIAID NIH HHS [K25 AI50436, K23 AI001794, K23 AI01794, K24 AI062476, K25 AI050436, P30 AI042851, P30 AI42851, R01 AI042006, R01 AI42006]; NIDA NIH HHS [K01 DA017179, K01 DA17179, K23 DA000523, K23 DA00523]; PHS HHS [290-01-0012] NR 48 TC 257 Z9 267 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2006 VL 44 IS 11 BP 990 EP 997 DI 10.1097/01.mlr.0000228021.89490.2a PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 104KF UT WOS:000241956600005 PM 17063130 ER PT J AU Wilkins, EG Lowery, JC Copeland, LA Goldfarb, SL Wren, PA Janz, NK AF Wilkins, Edwin G. Lowery, Julie C. Copeland, Laurel A. Goldfarb, Sherry L. Wren, Patricia A. Janz, Nancy K. TI Impact of an educational video on patient decision making in early breast cancer treatment SO MEDICAL DECISION MAKING LA English DT Article DE decision making; patient preferences; breast cancer ID BENIGN PROSTATIC HYPERPLASIA; ISCHEMIC-HEART-DISEASE; CONTROLLED-TRIAL; MEDICAL-CARE; INVOLVEMENT; SCALE; ATTITUDES; OUTCOMES; ILLNESS; PROGRAM AB Previous research suggests that patient education programs promoting shared decision making (SDM) may improve patient satisfaction and outcomes, yet controlled clinical trials are lacking. The authors evaluate the impact of an early breast cancer treatment educational video on patients' decisional preferences and behavior. Newly diagnosed stage I/stage II breast cancer patients were assigned to SDM video program or control groups in alternating months. Surveys were administered prior to the provider visit and 1 week following the treatment decision. Variables assessed included autonomy preferences, perceived involvement in care, satisfaction, and treatment choice. There were no significant intervention effects on informationol/decisional preferences, anxiety, knowledge, or satisfaction. Although 25% of SDM patients chose mastectomy compared to 14% of controls, this difference was not statistically significant. Eventhough enthusiasm for SDM programs remains high among some patients and providers, this study found only modest benefits. C1 Univ Michigan, Sect Plast Surg, Sch Med, Ann Arbor, MI 48109 USA. Vet Affairs Ann Arbor Healthcare Syst, HSR&D Ctr Excellence, Ann Arbor, MI USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78285 USA. Univ Michigan, Sch Med, Dept Emergency Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. RP Wilkins, EG (reprint author), Univ Michigan, Sect Plast Surg, Sch Med, 2130 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM ewilkins@umich.edu OI Copeland, Laurel/0000-0002-9478-0209 NR 26 TC 9 Z9 9 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2006 VL 26 IS 6 BP 589 EP 598 DI 10.1177/0272989X06295355 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 107LD UT WOS:000242172200004 PM 17099197 ER PT J AU Berbeco, RI Nishioka, S Shirato, H Jiang, SB AF Berbeco, Ross I. Nishioka, Seiko Shirato, Hiroki Jiang, Steve B. TI Residual motion of lung tumors in end-of-inhale respiratory gated radiotherapy based on external surrogates SO MEDICAL PHYSICS LA English DT Article DE radiotherapy; gating; residual motion; organ motion; breath coaching ID INSPIRATION BREATH-HOLD; REAL-TIME TUMOR; RADIATION-THERAPY SMART; DOSE-ESCALATION; TRACKING; CANCER; REPRODUCIBILITY; PRECISE; MARKERS AB It has been noted that some lung tumors exhibit large periodic motion due to respiration. To limit the amount of dose to healthy lung tissues, many clinics have begun gating radiotherapy treatment using externally placed surrogates. It has been observed by several institutions that the end-of-exhale (EOE) tumor position is more reproducible than other phases of the breathing cycle, so the gating window is often set there. From a treatment planning perspective, end-of-inhale (EOI) phase might be preferred for gating because the expanded lungs will further decrease the healthy tissue within the treatment field. We simulate gated treatment at the EOI phase, using a set of recently measured internal/external anatomy patient data. This paper attempts to answer three questions: (1) How much is the tumor residual motion when we use an external surrogate gating window at EOI? (2) How could we reduce the residual motion in the EOI gating window? (3) Is there a preference for amplitude- versus phase-based gating at EOI? We found that under free breathing conditions the residual motion of the tumors is much larger for EOI phase than for EOE phase. The mean values of residual motion at EOI were found to be 2.2 and 2.7 mm for amplitude- and phase-based gating, respectively, and, at EOE, 1.0 and 1.2 mm for amplitude- and phase-based gating, respectively. However, we note that the residual motion in the EOI gating window is correlated well with the reproducibility of the external surface position in the EOI phase. Using the results of a published breath-coaching study, we deduce that the residual motion of a lung tumor at EOI would approach that at EOE, with the same duty cycle (30%), under breath-coaching conditions. Additionally, we found that under these same conditions, phase-based gating approaches the same residual motion as amplitude-based gating, going from a 28% difference to 11%, for the patient with the largest difference between the two gating modalities. We conclude that it is feasible to achieve the same reproducibility of tumor location at EOT as at EOE if breath coaching is implemented, enabling us to reap the benefits of the dosimetric advantage of EOI gating. (c) 2006 American Association of Physicists in Medicine. C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NTT Hosp, Dept Radiol, Sapporo, Hokkaido, Japan. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berbeco, RI (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. EM rberbeco@lroc.harvard.edu RI Shirato, Hiroki/A-7068-2010 NR 20 TC 46 Z9 46 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2006 VL 33 IS 11 BP 4149 EP 4156 DI 10.1118/1.2358197 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 108PD UT WOS:000242250800019 PM 17153393 ER PT J AU Rietzel, E Chen, GTY AF Rietzel, Eike Chen, George T. Y. TI Deformable registration of 4D computed tomography data SO MEDICAL PHYSICS LA English DT Article DE deformable registration; 4DCT; 4D radiotherapy; organ motion ID IMAGE REGISTRATION; NONRIGID REGISTRATION; 4-DIMENSIONAL MODEL; RESPIRATORY MOTION; MUTUAL INFORMATION; MR-IMAGES; CT; PROSTATE; RADIOTHERAPY; VALIDATION AB Four-dimensional radiotherapy requires deformable registration to track delivered dose across varying anatomical states. Deformable registration based on B-splines was implemented to register 4D computed tomography data to a reference respiratory phase. To assess registration performance, anatomical landmarks were selected across ten respiratory phases in five patients. These point landmarks were transformed according to global registration parameters between different respiratory phases. Registration uncertainties were computed by subtraction of transformed and reference landmark positions. The selection of appropriate registration masks to separate independently moving anatomical subunits is crucial to registration performance. The average registration error for five landmarks for each of five patients was 2.1 mm. This level of accuracy is acceptable for most radiotherapy applications. (c) 2006 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Gesell Schwerionenforsch mbH, Biophys Abt, D-64291 Darmstadt, Germany. RP Rietzel, E (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM eike@rietzel.net FU PHS HHS [P01 21239] NR 28 TC 67 Z9 70 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2006 VL 33 IS 11 BP 4423 EP 4430 DI 10.1118/1.2361077 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 108PD UT WOS:000242250800047 PM 17153421 ER PT J AU Winder, WW Taylor, EB Thomson, DM AF Winder, William W. Taylor, Eric B. Thomson, David M. TI Role of AMP-activated protein kinase in the molecular adaptation to endurance exercise SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE endurance training; GLUT4; hexokinase; LKB1; mitochondria; PGC-1 alpha ID ACETYL-COA CARBOXYLASE; HUMAN SKELETAL-MUSCLE; CONTROLLING MITOCHONDRIAL BIOGENESIS; TRANSCRIPTIONAL COACTIVATOR PGC-1; STIMULATED GLUCOSE-UPTAKE; MESSENGER-RNA EXPRESSION; RAT MUSCLES; EPITROCHLEARIS MUSCLE; PROLONGED EXERCISE; MAMMALIAN TARGET AB What are the molecular signals induced by muscle contraction that result in an increase in GLUT4, hexokinase 2, mitochondrial oxidative enzymes, and other adaptations to endurance exercise training? Could repetitive activation of AMP-activated protein kinase (AMPK) be responsible in part? There is substantial evidence for a role of AMPK in inducing adaptations to endurance training: 1) AMPK is activated in response to muscle contraction; 2) chronic chemical activation of AMPK results in increases in GLUT4, hexokinase 2, UCP-3, and citric acid cycle enzymes; 3) muscle contraction and chemical activation of AMPK both result in increases in PGC-1 alpha, a transcriptional coactivator involved in stimulation of mitochondiial biogenesis; and 4) increases in muscle PGC-1 alpha, delta-aminolevulinic acid synthetase, and mitochondrial DNA induced by chronic creatine phosphate depletion in wild-type mice are not observed in dominant-negative AMPK mice. These observations lend credence to the hypothesis that AMPK activation induced by muscle contraction is responsible in part for adaptations to endurance exercise training. C1 Brigham Young Univ, Dept Physiol & Dev Biol, Provo, UT 84602 USA. Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. RP Winder, WW (reprint author), Brigham Young Univ, Dept Physiol & Dev Biol, 545 WIDB, Provo, UT 84602 USA. EM William_winder@byu.edu NR 55 TC 58 Z9 58 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2006 VL 38 IS 11 BP 1945 EP 1949 DI 10.1249/01.mss.0000233798.62153.50 PG 5 WC Sport Sciences SC Sport Sciences GA 103ZX UT WOS:000241926800010 PM 17095928 ER PT J AU Fischman, AJ Badgaiyan, RD AF Fischman, Alan J. Badgaiyan, Rajendra D. TI Cortical activations, psychiatric symptoms, and climacteric women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID CHRONIC-FATIGUE-SYNDROME; ORBITOFRONTAL CORTEX; MENOPAUSAL STATUS; PREFRONTAL CORTEX; MAJOR DEPRESSION; HORMONES; TRANSITION; MEMORY; VOLUME C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med, Boston, MA USA. RP Fischman, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med, Boston, MA USA. NR 21 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2006 VL 13 IS 6 BP 856 EP 858 DI 10.1097/01.gme.0000243577.86193.15 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 108QT UT WOS:000242255000003 PM 17077750 ER PT J AU Park, J Toner, M Yarmush, ML Tilles, AW AF Park, Jaesung Toner, Mehmet Yarmush, Martin L. Tilles, Arno W. TI Microchannel bioreactors for bioartificial liver support SO MICROFLUIDICS AND NANOFLUIDICS LA English DT Article DE oxygen; hepatocyte; microgrooves; bioreactor; shear stress ID OXYGEN-UPTAKE RATES; I CLINICAL-TRIAL; PHASE-I; CULTURED-HEPATOCYTES; HEPATIC-FAILURE; EXPERIENCE; PERFUSION; SYSTEM; CELLS; MULTICENTER AB An extracorporeal bioartificial liver (BAL) device containing viable hepatocytes has the potential to provide temporary hepatic support to liver failure patients, serving as a bridge to transplantation while awaiting a suitable donor. In some patients, providing temporary hepatic support may be sufficient to allow adequate regeneration of the host liver, thereby eliminating the need for a liver transplant. Although the BAL device is a promising technology for the treatment of liver failure, there are several technical challenges that must be overcome in order to develop systems with sufficient processing capacity and of manageable size. In this study, the authors describe the critical issues involved in developing a BAL device. They also discuss their experiences in hepatocyte culture optimization within the context of a microchannel flat-plate BAL device. C1 Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tilles, AW (reprint author), Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM arno_tilles@hms.harvard.edu NR 37 TC 7 Z9 7 U1 1 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1613-4982 J9 MICROFLUID NANOFLUID JI Microfluid. Nanofluid. PD NOV PY 2006 VL 2 IS 6 BP 525 EP 535 DI 10.1007/s10404-006-0095-6 PG 11 WC Nanoscience & Nanotechnology; Instruments & Instrumentation; Physics, Fluids & Plasmas SC Science & Technology - Other Topics; Instruments & Instrumentation; Physics GA 108FL UT WOS:000242225600007 ER PT J AU Sharma, VM Calvo, JA Draheim, KM Cunningham, LA Hermance, N Beverly, L Krishnamoorthy, V Bhasin, M Capobianco, AJ Kelliher, MA AF Sharma, Vishva Mitra Calvo, Jennifer A. Draheim, Kyle M. Cunningham, Leslie A. Hermance, Nicole Beverly, Levi Krishnamoorthy, Veena Bhasin, Manoj Capobianco, Anthony J. Kelliher, Michelle A. TI Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GAMMA-SECRETASE CLEAVAGE; ANKYRIN-REPEAT PROTEIN; INTRACELLULAR DOMAIN; TUMOR-SUPPRESSOR; TRANSGENIC MICE; RECEPTOR; ACTIVATION; LEUKEMOGENESIS; TRANSCRIPTION AB Recent work with mouse models and human leukemic samples has shown that gain-of-function mutation(s) in Notch1 is a common genetic event in T-cell acute lymphoblastic leukemia (T-ALL). The Notch1 receptor signals through a gamma-secretase-dependent process that releases intracellular Notch1 from the membrane to the nucleus, where it forms part of a transcriptional activator complex. To identify Notch1 target genes in leukemia, we developed mouse T-cell leukemic lines that express intracellular Notch1 in a doxycycline-dependent manner. Using gene expression profiling and chromatin immunoprecipitation, we identified c-myc as a novel, direct, and critical Notch1 target gene in T-cell leukemia. c-myc mRNA levels are increased in primary mouse T-cell tumors that harbor Notch1 mutations, and Notch1 inhibition decreases c-myc mRNA levels and inhibits leukemic cell growth. Retroviral expression of c-myc, like intracellular Notch1, rescues the growth arrest and apoptosis associated with gamma-secretase inhibitor treatment or Notch1 inhibition. Consistent with these findings, retroviral insertional mutagenesis screening of our T-cell leukemia mouse model revealed common insertions in either notch1 or c-myc genes. These studies define the Notch1 molecular signature in mouse T-ALL and importantly provide mechanistic insight as to how Notch1 contributes to human T-ALL. C1 Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA. RP Kelliher, MA (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, 364 Plantat St, Worcester, MA 01605 USA. EM michelle.kelliher@umassmed.edu FU NCI NIH HHS [R01 CA096899, CA-096889] NR 46 TC 158 Z9 164 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2006 VL 26 IS 21 BP 8022 EP 8031 DI 10.1128/MCB.001091-06 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 097QF UT WOS:000241462400018 PM 16954387 ER PT J AU Sicinska, E Lee, YM Gits, J Shigematsu, H Yu, QY Rebel, VI Geng, Y Marshall, CJ Akashi, K Dorfman, DM Touw, IP Sicinski, P AF Sicinska, Ewa Lee, Young-Mi Gits, Judith Shigematsu, Hirokazu Yu, Qunyan Rebel, Vivienne I. Geng, Yan Marshall, Christopher J. Akashi, Koichi Dorfman, David M. Touw, Ivo P. Sicinski, Piotr TI Essential role for cyclin D3 in granulocyte colony-stimulating factor-driven expansion of neutrophil granulocytes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INFANTILE GENETIC AGRANULOCYTOSIS; SEVERE CONGENITAL NEUTROPENIA; FACTOR-RECEPTOR; KOSTMANN-SYNDROME; MONOCYTOGENES INFECTION; MURINE LISTERIOSIS; DEPENDENT KINASES; BONE-MARROW; CELL-CYCLES; G-CSF AB The proliferation of neutrophil granulocyte lineage is driven largely by granulocyte colony-stimulating factor (G-CSF) acting via the G-CSF receptors. In this study, we show that mice lacking cyclin D3, a component of the core cell cycle machinery, are refractory to stimulation by the G-CSF. Consequently, cyclin D3-null mice display deficient maturation of granulocytes in the bone marrow and have reduced levels of neutrophil granulocytes in their peripheral blood. The mutant mice are unable to mount a normal response to bacterial challenge and succumb to microbial infections. In contrast, the expansion of hematopoietic stem cells and lineage-committed myeloid progenitors proceeds relatively normally in mice lacking cyclin D3, revealing that the requirement for cyclin D3 function operates at later stages of neutrophil development. Importantly, we verified that this requirement is specific to cyclin D3, as mice lacking other G(1) cyclins (D1, D2, E1, or E2) display normal granulocyte counts. Our analyses revealed that in the bone marrow cells of wild-type mice, activation of the G-CSF receptor leads to upregulation of cyclin D3. Collectively, these results demonstrate that cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they provide a molecular link of how G-CSF-dependent signaling triggers cell proliferation. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Erasmus Univ, Med Ctr, Inst Hematol, NL-3015 GE Rotterdam, Netherlands. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. Univ Texas, Ctr Hlth Sci, Dept Cell & Struct Biol, Childrens Canc Res Inst, San Antonio, TX 78229 USA. Inst Canc Res, Canc Res UK Ctr Cell & Mol Biol, London SW3 6JB, England. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Smith Res Bldg,44 Binney St, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [P01 CA109901, R01 CA108420] NR 42 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2006 VL 26 IS 21 BP 8052 EP 8060 DI 10.1128/MCB.00800-06 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 097QF UT WOS:000241462400021 PM 16954383 ER PT J AU Koh, HJ Arnolds, DE Fujii, N Tran, TT Rogers, MJ Jessen, N Li, YF Liew, CW Ho, RC Hirshman, MF Kulkarni, RN Kahn, CR Goodyear, LJ AF Koh, Ho-Jin Arnolds, David E. Fujii, Nobuharu Tran, Thien T. Rogers, Marc J. Jessen, Niels Li, Yangfeng Liew, Chong Wee Ho, Richard C. Hirshman, Michael F. Kulkarni, Rohit N. Kahn, C. Ronald Goodyear, Laurie J. TI Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves, glucose homeostasis, and decreases TRB3 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SERINE-THREONINE KINASE; AMPK ACTIVATION; MICE LACKING; AICAR TREATMENT; ADIPOSE-TISSUE; PPAR-ALPHA; CONTRACTION; RESISTANCE; GLYCOGEN AB LKB1 is a tumor suppressor that may also be fundamental to cell metabolism, since LKB1 phosphorylates and activates the energy sensing enzyme AMPK. We generated muscle-specific LKB1 knockout (MLKB1KO) mice, and surprisingly, found that a lack of LKB1 in skeletal muscle enhanced insulin sensitivity, as evidenced by decreased fasting glucose and insulin concentrations, improved glucose tolerance, increased muscle glucose uptake in vivo, and increased glucose utilization during a hyperinsulinemic-euglycemic clamp. MLKB1KO mice had increased insullin-stimulated Akt phosphorylation and a > 80% decrease in muscle expression of TRB3, a recently identified Akt inhibitor. Akt/TRB3 binding was present in skeletal muscle, and overexpression of TRB3 in C2Cl2 myoblasts significantly reduced Akt phosphorylation. These results demonstrate that skeletal muscle LKB1 is a negative regulator of insulin sensitivity and glucose homeostasis. LKB1-mediated TRB3 expression provides a novel link between LKB1 and Akt, critical kinases involved in both tumor genesis and cell metabolism. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect,Res Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014; OI Fujii, Nobuharu/0000-0002-0974-3033; Jessen, Niels/0000-0001-5613-7274 FU NIAMS NIH HHS [AR45670, F32AR04662, R01 AR045670]; NIDDK NIH HHS [DK36836, DK68626, P30 DK036836, P30 DK040561, P30 DK040561-11, R01 DK068626] NR 53 TC 121 Z9 122 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2006 VL 26 IS 22 BP 8217 EP 8227 DI 10.1128/MCB.00979-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 103ZQ UT WOS:000241926100001 PM 16966378 ER PT J AU Schuller, U Kho, AT Zhao, Q Ma, QF Rowitch, DH AF Schuller, Ulnch Kho, Alvin T. Zhao, Qing Ma, Qiufu Rowitch, David H. TI Cerebellar 'transcriptome' reveals cell-type and stage-specific expression during postnatal development and tumorigenesis SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE development; cerebellum; transcription factor; granule cells; Purkinje cells; interneurons; medulloblastoma; patched; transcriptome; brain tumor; cancer ID SONIC HEDGEHOG; N-MYC; MEDULLOBLASTOMA; PROLIFERATION; PRECURSORS; INTERNEURONS; MECHANISMS; PATHWAYS; MITOSIS; GROWTH AB Disorders of cerebellar development can result in neurological disease and cancer. The identity of transcription factors that may uniquely mark and/or regulate development of single cerebellar cell types, however, is poorly understood. We used a library of similar to 1100 probes for expression of transcription factor (TF)-encoding genes (> 70% of the mammalian 'transcriptome') to identify 227 genes with expression in developing neuronal and glial populations and 24 TFs that show cell-type- and stage-specific expression in granule cells, Purkinje cells and interneurons during postnatal cerebellar development. The utility of this panel is exemplified by analysis of medulloblastoma that shows upregulation of markers specific for early granule cell lineage, but not for other neuronal cell types, indicative of a unipotent precursor as well as a block in granule cell differentiation within the tumor. We propose that this atlas of the cerebellar transcriptome and the panel of 24 validated markers will be generally useful in analyses of mutations affecting postnatal cerebellar development and neoplasia. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Div Hematol, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Univ Calif San Francisco, Dept Pediat, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM rowitchd@peds.ucsf.edu FU NINDS NIH HHS [R01 NS047527] NR 40 TC 30 Z9 30 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD NOV PY 2006 VL 33 IS 3 BP 247 EP 259 DI 10.1016/j.mcn.2006.07.010 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 108FE UT WOS:000242224900003 PM 16962790 ER PT J AU Bradley, WD Hernandez, SE Settleman, J Koleske, AJ AF Bradley, William D. Hernandez, Samuel E. Settleman, Jeffrey Koleske, Anthony J. TI Integrin signaling through arg activates p190RhoGAP by promoting its binding to p120RasGAP and recruitment to the membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CELL-MATRIX ADHESIONS/; RHO FAMILY GTPASES; C-ABL; TYROSINE KINASE; PLECKSTRIN HOMOLOGY; FOCAL ADHESIONS; GROWTH-FACTORS; PROTEIN RHO; P120 GAP; DOMAIN AB The Rho family GTPases RhoA (Rho), Racl, and Cdc42 are essential effectors of integrin-mediated cell attachment and spreading. Rho activity, which promotes formation of focal adhesions and actin stress fibers, is inhibited upon initial cell attachment to allow sampling of the new adhesive environment. The Ab1-related gene (Arg) tyrosine kinase mediates adhesion-dependent inhibition of Rho through phosphorylation and activation of the Rho inhibitor p190RhoGAP-A (p190). p190 phosphorylation promotes its binding to p120RasGAP (p120). Here, we elucidate the mechanism by which p120 binding regulates p190 activation after adhesion. We show that p190 requires its p120-binding domain to undergo Arg-dependent activation in vivo. However, P120 binding does not activate p190RhoGAP activity in vitro. Instead, activation of p190 requires recruitment to the cell periphery. Integrin-mediated adhesion promotes relocalization. of p190 and p120 to the cell periphery in wild-type fibroblasts, but not in arg(-/-) fibroblasts. A dominant-negative p120 fragment blocks p190:p120 complex formation, prevents activation of p190 by adhesion, and disrupts the adhesion-dependent recruitment of p190 to the cell periphery. Our results demonstrate that integrin signaling through Arg activates p190 by promoting its association with p120, resulting in recruitment of p190 to the cell periphery where it inhibits Rho. C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Yale Univ, Interdept Neurosci Program, New Haven, CT 06520 USA. Yale Univ, Dept Neurobiol, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Koleske, AJ (reprint author), Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. EM anthony.koleske@yale.edu RI Bradley, William/C-3151-2011 FU NCI NIH HHS [R01 CA062142, CA62142]; NINDS NIH HHS [R01 NS039475, F31 NS042365, NS42365, NS39475] NR 46 TC 77 Z9 80 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2006 VL 17 IS 11 BP 4827 EP 4836 DI 10.1091/mbc.E06-02-0132 PG 10 WC Cell Biology SC Cell Biology GA 104XI UT WOS:000241993500021 PM 16971514 ER PT J AU Ren, J Raina, D Chen, W Li, GL Huang, L Kufe, D AF Ren, Jian Raina, Deepak Chen, Wen Li, Guilan Huang, Lei Kufe, Donald TI MUC1 oncoprotein functions in activation of fibroblast growth factor receptor signaling SO MOLECULAR CANCER RESEARCH LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; BETA-CATENIN; MULTIPLE-MYELOMA; BREAST-CARCINOMA; MONOCLONAL-ANTIBODY; C-SRC; CHROMOSOMAL TRANSLOCATION; GENE-TRANSCRIPTION; OXIDATIVE STRESS; CYTOPLASMIC TAIL AB Activation of the fibroblast growth factor (FGF) receptor 3 (FGFR3) has been linked to the development of human cancers by mechanisms that are not well understood. The MUC1 oncoprotein is aberrantly overexpressed by certain hematologic malignancies and most human carcinomas. The present studies show that MUC1 associates with FGFR3. Stimulation of cells with FGF1 increased the interaction between MUC1 and FGFR3. FGF1 stimulation also induced c-Src-dependent tyrosine phosphorylation of the MUC1 cytoplasmic domain on a YEKV motif. FGF1-induced tyrosine phosphorylation of MUC1 was associated with increased binding of MUC1 to beta-catenin and targeting of MUC1 and beta-catenin to the nucleus. FGF1 also induced binding of MUC1 to the heat shock protein 90 (HSP90) chaperone by a mechanism dependent on phosphorylation of the YEKV motif. Notably, beta-catenin and HSP90 compete for binding to the MUC1 cytoplasmic domain, indicating that MUC1 forms mutually exclusive complexes with these proteins. The results also show that inhibition of HSP90 with geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin attenuates FGF1-induced binding of MUC1 to HSP90 and targeting of MUC1 to the mitochondrial outer membrane. These findings indicate that FGF1 induces phosphorylation of MUC1 on YEKV and thereby activates two distinct pathways: (a) nuclear localization of MUC1 and beta-catenin and (b) delivery of MUC1 to mitochondria by HSP90. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [R01 CA042802-23, CA100707, CA97098, P50 CA100707, P50 CA100707-01, P50 CA100707-10, R01 CA042802, R01 CA097098, R01 CA097098-09] NR 61 TC 46 Z9 51 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2006 VL 4 IS 11 BP 873 EP 883 DI 10.1158/1541-7786.MCR-06-0204 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 107FE UT WOS:000242155300008 PM 17114345 ER PT J AU Zhang, Y Higashide, WM McCormick, BA Chen, J Zhou, DG AF Zhang, Ying Higashide, Wendy M. McCormick, Beth A. Chen, Jue Zhou, Daoguo TI The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase SO MOLECULAR MICROBIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; TYPHIMURIUM-CONTAINING VACUOLES; ENTERICA SEROVAR TYPHIMURIUM; PATHOGENICITY ISLAND 2; III SECRETION SYSTEM; CONJUGATING ENZYME; EFFECTOR PROTEINS; EPITHELIAL-CELLS; FAMILY; GENES AB Salmonella translocate a group of type III effectors into the host cells to induce entry, promote survival and cause intestinal inflammation. Although the biochemical and cellular mechanisms of how bacterial effectors function inside host cells remain largely unknown, studies have indicated that a likely strategy is to exploit host cellular pathways through functional mimicry. We report here that SopA, a Salmonella type III effector, mimics the mammalian HECT E3 ubiquitin ligase. SopA preferentially uses the host UbcH5a, UbcH5c and UbcH7 as E2s, which are involved in inflammation. Both the wild-type SopA and the mutant SopA(C753S) were expressed and translocated at similar levels during the infection of HeLa cells. A Salmonella strain expressing a catalytically incompetent SopA(C753S) mutant had reduced Salmonella-induced polymorphonuclear leukocytes transepithelial migration. We speculate that SopA ubiquitinate bacterial/host proteins involved in Salmonella-induced intestinal inflammation. C1 Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. Massachusetts Gen Hosp, Mucosal Immunol Labs, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Zhou, DG (reprint author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. EM zhoud@purdue.edu FU NIAID NIH HHS [AI49978] NR 48 TC 86 Z9 89 U1 4 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2006 VL 62 IS 3 BP 786 EP 793 DI 10.1111/j.1365-2958.2006.05407.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 094MT UT WOS:000241244200015 PM 17076670 ER PT J AU Anatelli, F Mroz, P Liu, Q Yang, C Castano, AP Swietlik, E Hamblin, MR AF Anatelli, Florencia Mroz, Pawel Liu, Qingde Yang, Changming Castano, Ana P. Swietlik, Emilia Hamblin, Michael R. TI Macrophage-targeted photosensitizer conjugate delivered by intratumoral injection SO MOLECULAR PHARMACEUTICS LA English DT Article DE tumor-associated macrophages; photosensitizer targeting; scavenger receptors; intratumoral injection; flow cytometry ID TUMOR-ASSOCIATED MACROPHAGES; INTERSTITIAL FLUID PRESSURE; NECROSIS-FACTOR-ALPHA; PHOTODYNAMIC THERAPY; COLORECTAL-CANCER; CELL-LINES; PROGRESSION; METASTASIS; PEGYLATION; CARCINOMA AB A conjugate between maleylated albumin and a photosensitizer (PS) shows cell type specific targeting to macrophages via the scavenger receptor. Administration of this conjugate to a tumor-bearing mouse followed by illumination may allow selective destruction of macrophages within tumors. There is accumulating evidence that tumor-associated macrophages contribute to tumor growth, invasiveness, metastasis, and immune suppression. We tested the intravenous (IV) injection of a conjugate between maleylated albumin and chlorin(e6) to BALB/c mice bearing three tumor types with differing proportions of tumor-associated macrophages. The accumulation of PS within the tumors after IV injection and 24 h incubation time was disappointing, and we therefore investigated intratumoral (IT) injection. This gave 20-50 times greater concentrations of PS within the tumor compared to IV injection as determined by tissue extraction. Furthermore the amounts of PS in each tumor type correlated well with the numbers of macrophages both as determined by extraction from bulk tumor and fluorescence quantification and as determined by tissue dissociation to a single cell suspension and two-color flow cytometry with macrophage-specific antibodies. IT injection of nonconjugated PS gave lower tumor accumulation that did not correlate with macrophage content. IT injection of targeted macromolecular delivery systems is an underexplored area and worthy of further study. C1 [Anatelli, Florencia; Mroz, Pawel; Liu, Qingde; Yang, Changming; Castano, Ana P.; Swietlik, Emilia; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Anatelli, Florencia; Mroz, Pawel; Liu, Qingde; Yang, Changming; Castano, Ana P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Swietlik, Emilia] Med Univ Warsaw, Inst Biostruct Res, Dept Immunol, Warsaw, Poland. [Hamblin, Michael R.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02142 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU National Cancer Institute [R01-CA/AI838801]; Department of Defense CDMRP Breast Cancer Research [W81XWH-04-1-0676]; UICC [ICR/05/103/2005] FX This work was supported by the National Cancer Institute (Grant R01-CA/AI838801 to M.R.H.). A.P.C. was supported by a Department of Defense CDMRP Breast Cancer Research Grant (W81XWH-04-1-0676). E.S. was supported by UICC Grant ICR/05/103/2005. We are grateful to John Demirs for help with histology. NR 44 TC 0 Z9 0 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD NOV-DEC PY 2006 VL 3 IS 6 BP 654 EP 664 DI 10.1021/mp060024y PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JM UT WOS:000203539800004 ER PT J AU Riggio, S Sano, M AF Riggio, Silvana Sano, Mary TI Neuropsychiatry - Introduction SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Editorial Material C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, Consultat Liaison Serv, Bronx, NY USA. RP Riggio, S (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 2006 VL 73 IS 7 BP 930 EP 930 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 116BB UT WOS:000242776400001 ER PT J AU Elder, GA De Gasperi, R Sosa, MAG AF Elder, Gregory A. De Gasperi, Rita Sosa, Miguel A. Gama TI Research update: Neurogenesis in adult brain and neuropsychiatric disorders SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE Alzheimer's disease; bromodeoxyuridine; depression; hippocampus; major affective disordeis; neural progenitors; neural stem cells; neurodegenerative diseases; neurogenesis; stem cell therapy ID NEURAL PROGENITOR CELLS; CORD STEM-CELLS; DENTATE GYRUS; HIPPOCAMPAL NEUROGENESIS; ALZHEIMERS-DISEASE; SUBVENTRICULAR ZONE; RAT HIPPOCAMPUS; IN-VITRO; ANTIDEPRESSANT TREATMENT; CEREBRAL METABOLITES AB Until recently neurogenesis in mammals was considered to occur only during the embryonic and early post-natal periods and to have no significant role in the adult nervous system. However, it is now accepted that neurogenesis occurs in two brain regions in adult mammals, namely, the hippocampus and olfactory bulb. In both regions new neurons arise from a resident population of neural progenitor cells that are maintained throughout adult life. Hippocampal neurogenesis is required for some types of hippocampal-dependent learning. Many factors enhance hippocampal neurogenesis including hormones, growth factors, drugs, neurotransmitters, and physical exercise as well as learning a hippocampal-dependent task. Other factors suppress hippocampal neurogenesis; these include aging, stress, glucocorticoids and stimuli that activate the pituitary/adrenal axis. Recently much attention has focused on the relevance of hippocampal neurogenesis to the pathophysiology and treatment of mood disorders. Indeed all major pharmacological and non-pharmacological treatments for depression enhance hippocampal neurogenesis and suppressing hippocampal neurogenesis in mice blocks behavioral responses in some antidepressant-sensitive tests. Altered hippocampal neurogenesis may also play a pathophysiological role in neurodegenerative disorders such as Alzheimer's disease. How much neurogenesis occurs normally in other brain regions is unclear. Neural progenitors are found throughout the neuraxis including both neurogenic and non-neurogenic regions. When cultured in vitro or isolated and transplanted back into neurogenic brain regions, these cells can differentiate into neurons, although in their in situ location they seem to behave as lineage-restricted glial progenitors. The environmental cues that limit the potential of progenitor cells in non-neurogenic brain regions are unknown. However, an emerging view is that astrocytes, a subset of which also functions as neural progenitor cells, are critical in regulating the local environment. After transplantation into adult brain, neural stem cells are capable of surviving and differentiating into both neurons and glial cells, offering hope that stem cell therapy may be utilized to treat a variety of neurological and perhaps psychiatric disorders. The widespread existence of endogenous neural progenitors even in non-neurogenic brain regions also offers hope that the potential of these cells may be harnessed to repair cellular injuries caused by injuries such as stroke, trauma or neurodegenerative diseases. While obstacles remain to both approaches, stem-cell-based therapies remain an area of intense research interest. Key Words: Alzheimer's disease, bromodeoxyuridine, depression, hippocampus, major affective disorders, neural progenitors, neural stem cells, neurodegenerative diseases, neurogenesis, stem cell therapy. C1 James J Peters Dept Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Elder, GA (reprint author), James J Peters Dept Vet Affairs Med Ctr, Psychiat Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu FU NIA NIH HHS [AG020139, AG023599]; NIMH NIH HHS [MH070603] NR 66 TC 56 Z9 63 U1 0 U2 18 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 2006 VL 73 IS 7 BP 931 EP 940 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 116BB UT WOS:000242776400002 PM 17195878 ER PT J AU Riggio, S AF Riggio, Silvana TI Psychiatric manifestations of nonconvulsive status epilepticus SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE nonconvulsive status epilepticus; absence status; complex partial status ID COMPLEX PARTIAL STATUS; CONVULSIVE STATUS EPILEPTICUS; ABSENCE-STATUS; CLINICAL-FEATURES; FRONTAL ORIGIN; LATER LIFE; ADULTS; POPULATION; MORBIDITY; MORTALITY AB Nonconvulsive status epilepticus (NCSE) is clinically characterized by altered mental status and the diagnosis is confirmed by electroencephalography. Absence status (AS) and complex partial status (CPS) are the two primary types of NCSE. Patients in NCSE may exhibit a wide range of clinical presentations including subtle memory deficits, bizarre behavior, psychosis, or coma. While prognosis is dependent on the underlying etiology and possibly related to duration of the event, there is limited research in this area. Treatment focuses on correcting underlying pathologic abnormalities such as hyponatremia or drug toxicity, and initiating pharmacologic therapy. The benzodiazepines are considered the first line treatment for both AS and CPS. C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. James J Peters VA Med Ctr, Consultat Liaison Serv, Bronx, NY USA. RP Riggio, S (reprint author), Mt Sinai Med Ctr, Dept Psychiat, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM silvana.rig-gio@mssm.edu NR 47 TC 13 Z9 14 U1 0 U2 1 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 2006 VL 73 IS 7 BP 960 EP 966 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 116BB UT WOS:000242776400005 PM 17195881 ER PT J AU Aloysi, A Van Dyk, K Sano, M AF Aloysi, Amy Van Dyk, Kathleen Sano, Mary TI Women's cognitive and affective health and neuropsychiatry SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE women's health; cognition; affect; estrogen ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN REPLACEMENT THERAPY; SURGICALLY MENOPAUSAL WOMEN; PLACEBO-CONTROLLED TRIAL; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND; PERIMENOPAUSAL WOMEN; VASOMOTOR SYMPTOMS; INITIATIVE MEMORY; MENSTRUAL-CYCLE AB Recent interest in women's health has focused on the cognitive consequences of aging and hormonal changes. Based on hypotheses about estrogenic effects in the central nervous system (CNS), large-scale clinical trials were designed to address the efficacy of hormone replacement on protection against dementia and cognitive decline. Surprisingly, an absence of risk reduction for dementia and cognitive loss was found and much reanalysis of these findings has focused on timing of hormone replacement. Here we take a broad perspective to address a fuller range of psychological health. Gender differences in other psychiatric conditions including depression and anxiety have been attributed to hormones, and the neurotransmitter systems that are implicated in affective disorders may have an impact on cognitive impairment as well. Hormonal influences on neurotrophic mechanisms, as well as neurotransmitter effects, may be responsible for a breadth of neuropsychiatric conditions, particularly in aging. This review will focus on cognition, mood and anxiety issues among women, with an emphasis on changes associated with aging. We will review data on the epidemiology of these entities and examine the biological mechanisms that may be involved, with an emphasis on those mechanisms that may contribute to the multiple aspects of neuropsychiatry and women's health. C1 James J Peters VA Med Ctr, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Alzheimer Dis Res Ctr, New York, NY 10029 USA. RP Sano, M (reprint author), James J Peters VA Med Ctr, 130 Kingsbridge Rd,Room 1F01, Bronx, NY 10468 USA. OI Van Dyk, Kathleen/0000-0003-1500-930X FU NIA NIH HHS [AG05138, AG10483, AG15922] NR 56 TC 12 Z9 12 U1 1 U2 4 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 2006 VL 73 IS 7 BP 967 EP 975 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 116BB UT WOS:000242776400006 PM 17195882 ER PT J AU Grossman, H Bergmann, C Parker, S AF Grossman, Hillel Bergmann, Christine Parker, Susan TI Dementia: A brief review SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Review DE aging; dementia; diagnosis; treatment; pathology; Alzheimer's disease; vascular dementia; Lewy Body disease; frontotemporal dementia ID APOLIPOPROTEIN-E EPSILON-4; FRONTOTEMPORAL LOBAR DEGENERATION; ISCHEMIC VASCULAR-DISEASE; ALZHEIMERS-DISEASE; LEWY BODIES; INTERNATIONAL WORKSHOP; ALPHA-SYNUCLEIN; DOUBLE-BLIND; TAU; RISK AB Dementia is an increasingly common diagnosis in our aging population, and the numbers are expected to rise exponentially in coming years. Alzheimer's disease alone now affects 4.5 million people in the US, while millions more are currently affected by vascular dementia, Lewy Body disease and frontotemporal dementia. Each of these is a distinct entity, though overlapping symptoms and comorbidities occur frequently. Within the past two decades research has progressed rapidly on multiple fronts, including epidemiology, etiology, pathology, diagnosis and treatment. It is important for clinicians to recognize early signs and symptoms of dementia, and to note critical differences among them. Dementia research has moved beyond description of symptoms and clinicopathological correlation to the elucidation of risk factors, the pathobiology of the disease process, and most important, to the first generation of dementia treatments. Our purpose here is to review the current state of knowledge and directions of research for the four major dementias noted above. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new disease-specific diagnostic tools and treatment modalities. C1 Mt Sinai Med Ctr, Dept Psychiat, Alzheimers Dis Res Ctr, New York, NY 10029 USA. James J Peters VA Med Ctr, Bronx, NY USA. RP Grossman, H (reprint author), Mt Sinai Med Ctr, Dept Psychiat, Alzheimers Dis Res Ctr, Box 1230, New York, NY 10029 USA. EM hillel.grossman@mssm.edu FU NIA NIH HHS [P60-AG005138] NR 61 TC 35 Z9 40 U1 4 U2 9 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 2006 VL 73 IS 7 BP 985 EP 992 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 116BB UT WOS:000242776400008 PM 17195884 ER PT J AU Chemerinski, E Levine, SR AF Chemerinski, Eran Levine, Steven R. TI Neuropsychiatric disorders following vascular brain injury SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE stroke; neuropsychiatric disorders; review ID POST-STROKE DEPRESSION; DOUBLE-BLIND TREATMENT; POSTSTROKE DEPRESSION; CEREBROVASCULAR LESIONS; MOOD DISORDERS; COGNITIVE IMPAIRMENT; GENERALIZED ANXIETY; SECONDARY MANIA; LEFT-HEMISPHERE; INTELLECTUAL IMPAIRMENT AB Several neuropsychiatric disorders such as mood, anxiety and psychotic disorders occur following cerebrovascular lesions. Post-stroke depression is the most common of these disorders and, along with post-stroke anxiety, has been shown to inhibit physical and cognitive recovery. Antidepressants have been shown to effectively treat post-stroke depression and to have a positive impact on rehabilitation efforts in patients suffering from this disorder. Much less is known about the potential impact of psychiatric conditions on recovery after stroke. Controlled trials will be able to adequately determine the effectiveness of treatment for these disorders. C1 Bronx Vet Adm Med Ctr, OOMH, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurol, Mt Sinai Stroke Ctr, New York, NY 10029 USA. RP Chemerinski, E (reprint author), Bronx Vet Adm Med Ctr, OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM eran.chemerinski@mssm.edu FU NINDS NIH HHS [K24NS43992, 1R01NS052417, P01NS23393, R01NS30896] NR 94 TC 32 Z9 41 U1 6 U2 12 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 2006 VL 73 IS 7 BP 1006 EP 1014 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 116BB UT WOS:000242776400011 PM 17195887 ER PT J AU Limsukon, A Saeed, AI Ramasamy, V Nalamati, J Dhuper, S AF Limsukon, Atikun Saeed, Ali Imran Ramasamy, Vimala Nalamati, Jhansi Dhuper, Sunil TI HIV-related pulmonary hypertension SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE HIV-related pulmonary hypertension; AIDS-related pulmonary disease; pulmonary hypertension; epoprostenol; highly active antiretroviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; ARTERIAL-HYPERTENSION; ANTIRETROVIRAL THERAPY; INFECTION; SURVIVAL; ARTERIOPATHY; PROSTACYCLIN; HEMOPHILIA; SILDENAFIL; BOSENTAN AB With the availability of better treatment and prophylactic regimens for the infectious complications of human immunodeficiency virus (HIV), the non-infectious complications are gaining greater attention. HIV-related pulmonary arterial hypertension (HIV-PAH) is one of these. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals. The pathogenesis remains unclear. Patients present with symptoms as diverse as progressive shortness of breath, pedal edema, dry cough, fatigue, syncope, as well as chest pain. Chest X-ray always shows cardiomegaly and prominent pulmonary artery, and evidence of tight ventricular hypertrophy can be seen from the electrocardiogram. The pulmonary arterial systolic pressure, diastolic pressure and pulmonary vascular resistance from right heart catheterization are increased. There are a few small studies showing the benefit of prostacyclin analog (epoprostenol and iloprost) and bosentan. The role of antiretrovirals remains controversial, as do those of other agents such as calcium channel blockers and anticoagulants. The prognosis of HIV-PAH is grave. Two thirds of HIV-PAH related mortality is usually secondary to consequences of pulmonary hypertension, with the worst survival noted in New York Heart Association (NYHA) functional class III-IV. The probability of survival in one series was 73%, 60% and 47% at one, two and three years, respectively. C1 Bronx Vet Affairs Med Ctr, Dept Internal Med, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. N Cent Bronx Hosp, Dept Internal Med, Bronx, NY USA. N Cent Bronx Hosp, Dept Pulm & Crit Care Med, Bronx, NY USA. N Cent Bronx Hosp, Dept Med, Bronx, NY USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Limsukon, A (reprint author), 130 S Flores St,Apt 310, Los Angeles, CA 90048 USA. EM atikhun@hotmail.com NR 35 TC 16 Z9 16 U1 0 U2 4 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 2006 VL 73 IS 7 BP 1037 EP 1044 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 116BB UT WOS:000242776400019 PM 17195895 ER PT J AU Shefner, JM Cudkowicz, M Brown, RH AF Shefner, Jeremy M. Cudkowicz, Merit Brown, Robert H., Jr. TI Motor unit number estimation predicts disease onset and survival in a transgenic mouse model of amyotrophic lateral sclerosis SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; motor unit; motor unit number estimation; outcome measure ID MICE; PROGRESSION; LOSSES AB Motor unit number estimation (MUNE) has proved useful in predicting rate of progression and survival in patients with amyotrophic lateral sclerosis (ALS). In animal models, it has demonstrated physiological effects of experimental medications that were not evident behaviorally. We sought to determine more specifically what aspects of function and survival that MUNE could predict in the G93A transgenic mouse model of ALS. Transgenic mice were examined in two distinct treatment studies, neither of which showed an effect of drug on survival, behavioral measures, or MUNE. MUNE was performed using a modification of the incremental stimulation method by stimulating the sciatic nerve at the sciatic notch, and recording with a circumferential surface electrode around the ipsilateral distal hindlimb. Both limbs were studied and the results averaged. MUNE was performed longitudinally on all animals from near onset to premorbid state. Each study was evaluated separately. For both studies, MUNE at initial study correlated significantly with behavioral determination of disease onset, and MUNE slope from initial to final study correlated significantly with disease duration, as measured from onset to time of death. However, the final MUNE value did not correlate with survival. Thus, in two studies involving animals with quite different disease courses, initial MUNE effectively predicted symptom onset and MUNE slope predicted survival. This suggests that MUNE has potential efficacy as a useful functional outcome measure in both animal and human studies of ALS. C1 Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Shefner, JM (reprint author), Upstate Med Univ, Dept Neurol, 750 E Adams St, Syracuse, NY 13210 USA. EM shefnerj@upstate.edu NR 23 TC 31 Z9 32 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD NOV PY 2006 VL 34 IS 5 BP 603 EP 607 DI 10.1002/mus.20628 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 099BQ UT WOS:000241567900007 PM 16892429 ER PT J AU Richardson, PG Mitsiades, CS Munshi, NC Anderson, KC AF Richardson, Paul G. Mitsiades, Constantine S. Munshi, Nikhil C. Anderson, Kenneth C. TI Can thalidomide improve outcome in patients with multiple myeloma? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE chemotherapy; hematopoietic stem-cell transplantation; multiple myeloma; thalidomide ID CHEMOTHERAPY; TRIAL C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. DFCI, Dept Med Oncol, Boston, MA USA. DFCI, JLMMC, Boston, MA USA. HMS, Boston, MA USA. DFCI, Div Hematol Neoplasia, Boston, MA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 8 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2006 VL 3 IS 11 BP 590 EP 591 DI 10.1038/ncponc0630 PG 2 WC Oncology SC Oncology GA 102VZ UT WOS:000241842700003 PM 17080171 ER PT J AU Duska, L AF Duska, Linda TI Can the utility of secondary cytoreduction for ovarian cancer be reliably established? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE ovarian cancer; secondary; cytoreduction; surgery ID CARCINOMA C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Duska, L (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, YAW 9,55 Fruit St, Boston, MA 02114 USA. EM lduska@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2006 VL 3 IS 11 BP 596 EP 597 DI 10.1038/ncponc0659 PG 2 WC Oncology SC Oncology GA 102VZ UT WOS:000241842700006 PM 17080174 ER PT J AU Heinrich, MC Corless, CL AF Heinrich, Michael C. Corless, Christopher L. TI Does tumor mutational status correlate with clinical response to imatinib? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE gastrointestinal stromal tumor; genotype analysis; imatinib; KIT; PDGFRA ID GASTROINTESTINAL STROMAL TUMORS C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Heinrich, MC (reprint author), Oregon Hlth Sci Univ, Dept Med, R&D-19,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM heinrich@ohsu.edu NR 5 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2006 VL 3 IS 11 BP 600 EP 601 DI 10.1038/ncponc0639 PG 2 WC Oncology SC Oncology GA 102VZ UT WOS:000241842700008 PM 17080176 ER PT J AU Baughman, JM Mootha, VK AF Baughman, Joshua M. Mootha, Vamsi K. TI Buffering mitochondrial DNA variation SO NATURE GENETICS LA English DT Editorial Material ID MTDNA; DISEASES; SEQUENCE AB Reactive oxygen species (ROS) are traditionally viewed as the toxic by-product of cellular respiration. A new study suggests a homeostatic role for ROS in maintaining stable respiratory phenotypes across genetic variants of the mitochondrial genome. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Baughman, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu NR 10 TC 10 Z9 11 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2006 VL 38 IS 11 BP 1232 EP 1233 DI 10.1038/ng1106-1232 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 099KH UT WOS:000241592700007 PM 17072298 ER PT J AU Lorenz-Depiereux, B Bastepe, M Benet-Pages, A Amyere, M Wagenstaller, J Muller-Barth, U Badenhoop, K Kaiser, SM Rittmaster, RS Shlossberg, AH Olivares, JL Loris, C Ramos, FJ Glorieux, F Vikkula, M Juppner, H Strom, TM AF Lorenz-Depiereux, Bettina Bastepe, Murat Benet-Pages, Anna Amyere, Mustapha Wagenstaller, Janine Mueller-Barth, Ursula Badenhoop, Klaus Kaiser, Stephanie M. Rittmaster, Roger S. Shlossberg, Alan H. Olivares, Jose L. Loris, Cesar Ramos, Feliciano J. Glorieux, Francis Vikkula, Miikka Juppner, Harald Strom, Tim M. TI DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis SO NATURE GENETICS LA English DT Article ID RICKETS; PHEX; MINERALIZATION; IDENTIFICATION; OSTEOMALACIA; SUBSTRATE; ROLES; FGF23; GENE AB Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH) 2D levels and suggesting that DMP1 may regulate FGF23 expression. C1 GSF, Inst Human Genet, Natl Res Ctr Environm & Hlth, D-85764 Neuherberg, Germany. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Catholique Louvain, B-1200 Brussels, Belgium. Christian Duve Inst, B-1200 Brussels, Belgium. Med Genet, D-63450 Hanau, Germany. Univ Hosp, Div Endocrinol Diabet & Metab, D-60590 Frankfurt, Germany. Queen Elizabeth II Hlth Sci Ctr, Div Endocrinol & Metab, Halifax, NS, Canada. Univ Zaragoza, Fac Med, Univ Hosp Lozano Blesa, Dept Pediat, E-50009 Zaragoza, Spain. Univ Zaragoza, Childrens Hosp Miguel Servet, Serv Nephrol, E-50009 Zaragoza, Spain. Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany. RP Juppner, H (reprint author), GSF, Inst Human Genet, Natl Res Ctr Environm & Hlth, D-85764 Neuherberg, Germany. EM jueppner@helix.mgh.harvard.edu; TimStrom@gsf.de OI Ramos Fuentes, Feliciano Jesus/0000-0002-5732-2209; Vikkula, Miikka/0000-0002-6236-338X FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-11, R21 DK075856, R21 DK075856-01, R37 DK046718] NR 15 TC 274 Z9 281 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2006 VL 38 IS 11 BP 1248 EP 1250 DI 10.1038/ng1868 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 099KH UT WOS:000241592700012 PM 17033625 ER PT J AU Carroll, JS Meyer, CA Song, J Li, W Geistlinger, TR Eeckhoute, J Brodsky, AS Keeton, EK Fertuck, KC Hall, GF Wang, QB Bekiranov, S Sementchenko, V Fox, EA Silver, PA Gingeras, TR Liu, XS Brown, M AF Carroll, Jason S. Meyer, Clifford A. Song, Jun Li, Wei Geistlinger, Timothy R. Eeckhoute, Jerome Brodsky, Alexander S. Keeton, Erika Krasnickas Fertuck, Kirsten C. Hall, Giles F. Wang, Qianben Bekiranov, Stefan Sementchenko, Victor Fox, Edward A. Silver, Pamela A. Gingeras, Thomas R. Liu, X. Shirley Brown, Myles TI Genome-wide analysis of estrogen receptor binding sites SO NATURE GENETICS LA English DT Article ID BREAST-CANCER CELLS; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; GLUCOCORTICOID-RECEPTOR; ACTIVATION; PROMOTER; REVEALS; AP-1; CHROMOSOME-22; PROGRESSION AB The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation, particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer. 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 Publ Hlth, Boston, MA 02115 USA. Brown Univ, Labs Mol Med, Ctr Genom & Proteom, Providence, RI 02903 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Affymetrix, Santa Clara, CA 95051 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu; myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; Li, Wei/A-8544-2009; Wang, Qianben/E-4267-2011; OI Gingeras, Thomas/0000-0001-9106-3573; Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 FU NCI NIH HHS [CA089393]; NHGRI NIH HHS [R01 HG004069, R01 HG004069-01]; NIDDK NIH HHS [DK074967] NR 49 TC 802 Z9 818 U1 6 U2 48 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2006 VL 38 IS 11 BP 1289 EP 1297 DI 10.1038/ng1901 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 099KH UT WOS:000241592700017 PM 17013392 ER PT J AU de Bakker, PIW Burtt, NP Graham, RR Guiducci, C Yelensky, R Drake, JA Bersaglieri, T Penney, KL Butler, J Young, S Onofrio, RC Lyon, HN O Stram, D Haiman, CA Freedman, ML Zhu, XF Cooper, R Groop, L Kolonel, LN Henderson, BE Daly, MJ Hirschhorn, JN Altshuler, D AF de Bakker, Paul I. W. Burtt, Noel P. Graham, Robert R. Guiducci, Candace Yelensky, Roman Drake, Jared A. Bersaglieri, Todd Penney, Kathryn L. Butler, Johannah Young, Stanton Onofrio, Robert C. Lyon, Helen N. O Stram, Daniel Haiman, Christopher A. Freedman, Matthew L. Zhu, Xiaofeng Cooper, Richard Groop, Leif Kolonel, Laurence N. Henderson, Brian E. Daly, Mark J. Hirschhorn, Joel N. Altshuler, David TI Transferability of tag SNPs in genetic association studies in multiple populations SO NATURE GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM PATTERNS; SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN GENOME; MULTIETHNIC COHORT; HAPMAP; EFFICIENCY; PERFORMANCE; PORTABILITY; DIVERSITY; SELECTION AB A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world. C1 Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Childrens Hosp, Div Endocrinol, Program Genom, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Program Genom, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Loyola Univ, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. Lund Univ, Univ Hosp, Dept Clin Sci, S-20502 Malmo, Sweden. Univ Helsinki, Dept Med, Helsinki, Finland. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Altshuler, D (reprint author), Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 FU NCI NIH HHS [CA098758, CA54281, CA63464]; NHLBI NIH HHS [HL074166]; NIDDK NIH HHS [DK067288] NR 30 TC 163 Z9 163 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2006 VL 38 IS 11 BP 1298 EP 1303 DI 10.1038/ng1899 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 099KH UT WOS:000241592700018 PM 17057720 ER PT J AU Li, LQ Iwamoto, Y Berezovskaya, A Boussiotis, VA AF Li, Lequn Iwamoto, Yoshiko Berezovskaya, Alla Boussiotis, Vassiliki A. TI A pathway regulated by cell cycle inhibitor p27(Kip1) and checkpoint inhibitor Smad3 is involved in the induction of T cell tolerance SO NATURE IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; DEPENDENT-KINASE; DOWN-REGULATION; TGF-BETA; TARGETED DISRUPTION; EFFECTOR FUNCTION; CLONAL EXPANSION; MICE LACKING; G(1) ARREST; IN-VIVO AB Peripheral tolerance is essential for immunological homeostasis. Tolerant T cells are thought to arise after T cell receptor ligation in conditions that are nonpermissive for replication. Here we have investigated the function of the cell cycle inhibitor p27(Kip1) in tolerance induction in vivo using naive T cell receptor - transgenic cells lacking the cyclin-dependent kinase ( Cdk) - binding domain of p27(Kip1)( p27 Delta). Wild-type but not p27 Delta cells underwent tolerization. Tolerized wild-type cells had impaired Cdk2 and Cdc2 kinase activity and failed to phosphorylate the checkpoint inhibitor Smad3, leading to enhanced expression of the Cdk inhibitor p15. In contrast, p27 Delta cells proliferated in tolerizing conditions because of Cdk kinase activation and phosphorylation of Smad3, which resulted in no upregulation of p15. Smad3 'knockdown' prevented tolerance induction, whereas expression of a Smad3 mutant resistant to Cdk-mediated phosphorylation recapitulated molecular and functional events of tolerance. Thus, p27(Kip1) is required during induction of tolerance and Smad3 regulates T cell responses 'downstream' of p27(Kip1). C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Hematol & Oncol, Boston, MA 02129 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. EM vboussiotis@partners.org FU NCI NIH HHS [CA104596]; NIAID NIH HHS [AI 46548, AI 043552] NR 44 TC 60 Z9 62 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2006 VL 7 IS 11 BP 1157 EP 1165 DI 10.1038/ni1398 PG 9 WC Immunology SC Immunology GA 097HF UT WOS:000241437200010 PM 17013388 ER PT J AU Ariel, A Fredman, G Sun, YP Kantarci, A Van Dyke, TE D Luster, A Serhan, CN AF Ariel, Amiram Fredman, Gabrielle Sun, Yee-Ping Kantarci, Alpdogan Van Dyke, Thomas E. D Luster, Andrew Serhan, Charles N. TI Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression SO NATURE IMMUNOLOGY LA English DT Article ID RECEPTOR SPECIFICITY; AUTOIMMUNE-DISEASE; IMPAIRED CLEARANCE; STABLE ANALOGS; TGF-BETA; IN-VIVO; INFLAMMATION; PHAGOCYTOSIS; ASPIRIN; LIPOXINS AB During the resolution phase of inflammation, the 'corpses' of apoptotic leukocytes are gradually cleared by macrophages. Here we report that during the resolution of peritonitis, the CCR5 chemokine receptor ligands CCL3 and CCL5 persisted in CCR5-deficient mice. CCR5 expression on apoptotic neutrophils and activated apoptotic T cells sequestered and effectively cleared CCL3 and CCL5 from sites of inflammation. CCR5 expression on late apoptotic human polymorphonuclear cells was downregulated by proinflammatory stimuli, including tumor necrosis factor, and was upregulated by 'proresolution' lipid mediators, including lipoxin A(4), resolvin E1 and protectin D1. Our results suggest that CCR5(+) apoptotic leukocytes act as 'terminators' of chemokine signaling during the resolution of inflammation. C1 Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Periodontol & Oral Biol, Goldman Sch Grad Dent, Boston, MA 02118 USA. Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Charlestown, MA 02129 USA. RP Serhan, CN (reprint author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM cnserhan@zeus.bwh.harvard.edu FU NCRR NIH HHS [M01 RR000533]; NIDCR NIH HHS [P50 DE016191, P50-DE016191]; NIDDK NIH HHS [DK-074448, DK-074449, R01 DK074448, R01 DK074449]; NIGMS NIH HHS [R37 GM038765, GM38765, R01 GM038765] NR 50 TC 182 Z9 189 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2006 VL 7 IS 11 BP 1209 EP 1216 DI 10.1038/ni1392 PG 8 WC Immunology SC Immunology GA 097HF UT WOS:000241437200016 PM 17013391 ER PT J AU Tegeder, I Costigan, M Griffin, RS Abele, A Belfer, I Schmidt, H Ehnert, C Nejim, J Marian, C Scholz, J Wu, TX Allchorne, A Diatchenko, L Binshtok, AM Goldman, D Adolph, J Sama, S Atlas, SJ Carlezon, WA Parsegian, A Lotsch, J Fillingim, RB Maixner, W Geisslinger, G Max, MB Woolf, CJ AF Tegeder, Irmgard Costigan, Michael Griffin, Robert S. Abele, Andrea Belfer, Inna Schmidt, Helmut Ehnert, Corina Nejim, Jemiel Marian, Claudiu Scholz, Joachim Wu, Tianxia Allchorne, Andrew Diatchenko, Luda Binshtok, Alexander M. Goldman, David Adolph, Jan Sama, Swetha Atlas, Steven J. Carlezon, William A. Parsegian, Aram Loetsch, Joern Fillingim, Roger B. Maixner, William Geisslinger, Gerd Max, Mitchell B. Woolf, Clifford J. TI GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence SO NATURE MEDICINE LA English DT Article ID PERIPHERAL-NERVE INJURY; MAINE LUMBAR SPINE; NITRIC-OXIDE; DORSAL-HORN; I GENE; LAPAROSCOPIC CHOLECYSTECTOMY; NONSURGICAL MANAGEMENT; GABAERGIC INHIBITION; NEUROPATHIC PAIN; PROTEIN AB We report that GTP cyclohydrolase (GCH1), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, is a key modulator of peripheral neuropathic and inflammatory pain. BH4 is an essential cofactor for catecholamine, serotonin and nitric oxide production. After axonal injury, concentrations of BH4 rose in primary sensory neurons, owing to upregulation of GCH1. After peripheral inflammation, BH4 also increased in dorsal root ganglia (DRGs), owing to enhanced GCH1 enzyme activity. Inhibiting this de novo BH4 synthesis in rats attenuated neuropathic and inflammatory pain and prevented nerve injury-evoked excess nitric oxide production in the DRG, whereas administering BH4 intrathecally exacerbated pain. In humans, a haplotype of the GCH1 gene (population frequency 15.4%) was significantly associated with less pain following diskectomy for persistent radicular low back pain. Healthy individuals homozygous for this haplotype exhibited reduced experimental pain sensitivity, and forskolinstimulated immortalized leukocytes from haplotype carriers upregulated GCH1 less than did controls. BH4 is therefore an intrinsic regulator of pain sensitivity and chronicity, and the GTP cyclohydrolase haplotype is a marker for these traits. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Frankfurt, Pharmazentrum, Inst Klin Pharmakol, Zentrum Arzneimittelforsch Entwicklung & Sicherhe, D-60590 Frankfurt, Germany. NIAAA, Neurogenet Lab, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Ctr Neurosensory Disorders, Sch Dent, Chapel Hill, NC 27599 USA. Univ Florida, Coll Dent, Gainesville, FL 32608 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Belmont, MA 02478 USA. Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20892 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM cwoolf@partners.org RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lotsch, Jorn/0000-0002-5818-6958; Tegeder, Irmgard/0000-0001-7524-8025 FU NIAAA NIH HHS [Z01 AA000301]; NIDCR NIH HHS [DE07509, DE16558, Z01 DE00366]; NINDS NIH HHS [NS038253, NS039518, NS045685, NS052623] NR 49 TC 299 Z9 313 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2006 VL 12 IS 11 BP 1269 EP 1277 DI 10.1038/nm1490 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 102WU UT WOS:000241844900024 PM 17057711 ER PT J AU Ozdinler, PH Macklis, JD AF Ozdinler, P. Hande Macklis, Jeffrey D. TI IGF-I specifically enhances axon outgrowth of corticospinal motor neurons SO NATURE NEUROSCIENCE LA English DT Article ID GROWTH-FACTOR-I; AMYOTROPHIC-LATERAL-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; RETINAL GANGLION-CELLS; NEUROTROPHIC FACTOR; PROJECTION NEURONS; POSTNATAL-DEVELOPMENT; CONTROLLED-TRIAL; SPINAL-CORD; SURVIVAL AB Corticospinal motor neurons ( CSMN) are among the most complex CNS neurons; they control voluntary motor function and are prototypical projection neurons. In amyotrophic lateral sclerosis ( ALS), both spinal motor neurons and CSMN degenerate; their damage contributes centrally to the loss of motor function in spinal cord injury. Direct investigation of CSMN is severely limited by inaccessibility in the heterogeneous cortex. Here, using new CSMN purification and culture approaches, and in vivo analyses, we report that insulin-like growth factor-1 ( IGF-I) specifically enhances the extent and rate of murine CSMN axon outgrowth, mediated via the IGF-I receptor and downstream signaling pathways; this is distinct from IGF-I support of neuronal survival. In contrast, brain-derived neurotrophic factor ( BDNF) enhances branching and arborization, but not axon outgrowth. These experiments define specific controls over directed differentiation of CSMN, indicate a distinct role of IGF-I in CSMN axon outgrowth during development, and might enable control over CSMN derived from neural precursors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci, Boston, MA 02114 USA. Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu FU NINDS NIH HHS [NS41590, NS45523, NS49553] NR 50 TC 166 Z9 169 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2006 VL 9 IS 11 BP 1371 EP 1381 DI 10.1038/nn1789 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 110TN UT WOS:000242403800014 PM 17057708 ER PT J AU Li, G Cherrier, MM Tsuang, DW Petrie, EC Colasurdo, EA Craft, S Schellenberg, GD Peskind, ER Raskind, MA Wilkinson, CW AF Li, Ge Cherrier, Monique M. Tsuang, Debby W. Petrie, Eric C. Colasurdo, Elizabeth A. Craft, Suzanne Schellenberg, Gerard D. Peskind, Elaine R. Raskind, Murray A. Wilkinson, Charles W. TI Salivary cortisol and memory function in human aging SO NEUROBIOLOGY OF AGING LA English DT Article DE cortisol; hypothalamic-pituitary-adrenal; memory; cognitive function; longitudinal study; aging ID MEDIAL PREFRONTAL CORTEX; HEALTHY ELDERLY SUBJECTS; AGE-RELATED-CHANGES; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; FEEDBACK INHIBITION; PYRAMIDAL NEURONS; SENILE-DEMENTIA; DENDRITIC REORGANIZATION; CIRCADIAN RHYTHMICITY AB Objective: To examine the association of salivary cortisol with cognitive changes in a 3 year longitudinal study. Previous studies have suggested that elevated glucocorticoid concentrations alter hippocampal neuronal morphology, inhibit neurogenesis, and impair cognition. Methods: Salivary cortisol samples were collected at home by 79 cognitively intact older persons (mean age 78 +/- 7 years) at 08:00, 15:00 and 23:00 h, and collections were repeated annually for 3 years. Cognitive function was also assessed annually. Results: The mean cortisol level of samples taken at three times of day and the cortisol concentration at 23:00 h were significantly associated with poorer performance on tasks of declarative memory and executive function. Of 46 subjects who completed the entire 3 year study, higher initial cortisol concentration at 23:00 h predicted a decline in performance of delayed paragraph recall. Conclusion: These results partially confirm previous findings that high cortisol is associated with impaired declarative memory function in non-demented older persons. In addition, our data show that high salivary cortisol concentrations predict a decline in memory function over the next 3 years. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Li, G (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM gli@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [P50 AG05136, R01 AG08419, R35 AG010917] NR 79 TC 69 Z9 70 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2006 VL 27 IS 11 BP 1705 EP 1714 DI 10.1016/j.neurobiolaging.2005.09.031 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 090RU UT WOS:000240969500016 PM 16274857 ER PT J AU Kishikawa, S Li, JL Gillis, T Hakky, MM Warby, S Hayden, M MacDonald, ME Myers, RH Gusella, JF AF Kishikawa, Shotaro Li, Jian-Liang Gillis, Tammy Hakky, Michael M. Warby, Simon Hayden, Michael MacDonald, Marcy E. Myers, Richard H. Gusella, James F. TI Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington's disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease (HD); brain-derived neurotrophic factor (BDNF); age at onset; genetic modifier; functional polymorphism ID BDNF VAL66MET POLYMORPHISM; ACTIVITY-DEPENDENT SECRETION; NEURONS IN-VITRO; ALZHEIMERS-DISEASE; FACTOR GENE; SUBSTANCE-ABUSE; HUMAN-MEMORY; OF-ONSET; ASSOCIATION; DISORDER AB In Huntington's disease (HD), genetic factors in addition to the HD CAG repeat mutation play a significant role in determining age at neurologic onset. Brain-derived neurotrophic factor (BDNF), a survival factor for striatal neurons, has been implicated as a target of regulation by huntingtin and is an attractive candidate as a genetic modifier. We tested this hypothesis by genotyping a SNP known to alter BDNF function (rs6265, also termed Va166NIet) and a SNP associated with Alzheimer disease (BDNF C270T), along with two BDNF intronic SNPs (rs7103411, rs11030104), in 228 cases with extreme young onset and 329 cases with extreme old onset of ED. No differences were seen between groups for allele frequencies or genotype frequencies for any SNP. Furthermore, no association to onset age was seen in GEE models controlling for HD repeat size or in haplotype analyses of these SNPs. These results indicate that BDNF does not influence significantly the mechanisms in ED pathogenesis that lead to neurologic onset. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, CPZ5830,185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu RI Hayden, Michael/D-8581-2011; OI Hayden, Michael/0000-0001-5159-1419; Li, Jian-Liang/0000-0002-6487-081X; Myers, Richard/0000-0002-8365-2674 FU NINDS NIH HHS [NS16375, NS32765, P50NS016367] NR 44 TC 19 Z9 19 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2006 VL 24 IS 2 BP 280 EP 285 DI 10.1016/j.nbd.2006.07.008 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 099LA UT WOS:000241594900007 PM 16962786 ER PT J AU Pisani, A Martella, G Tscherter, A Bonsi, P Sharma, N Bernardi, G Standaert, DG AF Pisani, A. Martella, G. Tscherter, A. Bonsi, P. Sharma, N. Bernardi, G. Standaert, D. G. TI Altered responses to dopaminergic D2 receptor activation and N-type calcium currents in striatal cholinergic interneurons in a mouse model of DYT1 dystonia SO NEUROBIOLOGY OF DISEASE LA English DT Article DE DYT1; dystonia; striatum; cholinergic interneurons; electrophysiology; dopamine ID TONICALLY ACTIVE NEURONS; PROTEIN; TORSINA; ACETYLCHOLINE; INHIBITION; TRANSMISSION; NEOSTRIATUM; MODULATION; MUTATION; RELEASE AB Early-onset torsion dystonia (DYT1) is an autosomal dominant disease caused by a deletion in the gene encoding the protein torsinA. Recently, a transgenic mouse model of DYT1 has been described, expressing either the human wild-type torsinA (hWT) or mutant torsinA (hMT). We recorded the activity of striatal cholinergic interneurons of hWT, hMT, and control mice. In slice preparations, no significant differences were observed in resting membrane potential (RMP), firing activity, action potential duration or I-h current. Quinpirole, a D2-like dopamine receptor agonist, did not produce detectable effects on RMP of cholinergic interneurons in control mice and hWT mice, but in the hMT mice caused membrane depolarization and an increase in the firing rate. D2 receptor activation inhibits N-type high-voltage-activated calcium currents. We found that, in isolated interneurons from hMT mice, the quinpirole- mediated inhibition of N-type currents was significantly larger than in hWT and controls. Moreover, the N-type component was significantly over- represented in hMT mice. The altered sensitivity of N-type channels in hMT mice could account for the paradoxical excitatory effect of D2 stimulation. Our data support the existence of an imbalance between striatal dopaminergic and cholinergic signaling in DYTI dystonia. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Roma Tor Vergata, Neurol Clin, Dipartimento Neurosci, I-00135 Rome, Italy. European Brain Res Inst, Fdn Santa Lucia, IRCCS, CERC, Rome, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pisani, A (reprint author), Univ Roma Tor Vergata, Neurol Clin, Dipartimento Neurosci, Via Montpellier 1, I-00135 Rome, Italy. EM pisani@uniroma2.it RI Bonsi, Paola/K-4688-2012; OI Bonsi, Paola/0000-0001-5940-9028; Tscherter, Anne/0000-0002-6972-482X; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [K08 NS044272, NS37409] NR 35 TC 74 Z9 75 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2006 VL 24 IS 2 BP 318 EP 325 DI 10.1016/j.nbd.2006.07.006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 099LA UT WOS:000241594900011 PM 16934985 ER PT J AU Norden, AD Wen, PY AF Norden, Andrew D. Wen, Patrick Y. TI Glioma therapy in adults SO NEUROLOGIST LA English DT Review DE glioma; brain tumor; treatment ID LOW-GRADE GLIOMA; PHASE-II TRIAL; MEDICAL-RESEARCH-COUNCIL; NEUTRON-CAPTURE THERAPY; RECURRENT GLIOBLASTOMA-MULTIFORME; MONOCLONAL-ANTIBODY 81C6; TUMOR-SUPPRESSOR GENE; MALIGNANT GLIOMA; RADIATION-THERAPY; RANDOMIZED-TRIAL AB Background: Gliomas are the most common type of primary brain tumor. Nearly two-thirds of gliomas are highly malignant lesions that account for a disproportionate share of brain tumor-related morbidity and mortality. Despite recent advances, two-year survival for glioblastoma with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Review Summary: Surgery and radiation have been the mainstays of therapy for most glioma patients, but temozolomide chemotherapy has recently been proven to prolong overall survival in patients with glioblastoma. Intriguing data suggests that activity of O6-methylguanine-DNA methyltransferase (MGMT), in tumor cells may predict responsiveness to temozolomide and other alkylating agents. Novel treatment approaches, especially targeted molecular therapies against critical components of glioma signaling pathways, appear promising in preliminary studies. Optimal treatment for patients with low-grade gliomas has yet to be determined. Advances in oligodendroglioma biology have identified loss of chromosomes 1p and 19q as powerful indicators of a favorable prognosis. These same changes may predict response to chemotherapy. Conclusions: Though the prognosis for many patients with gliomas is poor, the last decade produced a number of important advances, some of which have translated directly into survival benefits. Rapid progress in the field of glioma molecular biology continues to identify therapeutic targets and provide hope for the future of this challenging disease. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Div Canc Neurol, Boston, MA 02115 USA. Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. RP Wen, PY (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Div Canc Neurol, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org NR 139 TC 64 Z9 73 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD NOV PY 2006 VL 12 IS 6 BP 279 EP 292 DI 10.1097/01.nrl.0000250928.26044.47 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 109YP UT WOS:000242345800001 PM 17122724 ER PT J AU Samuelson, KW Neylan, TC Metzler, TJ Lenoci, M Rothlind, J Henn-Haase, C Choucroun, G Weiner, MW Marmar, CR AF Samuelson, Kristin W. Neylan, Thomas C. Metzler, Thomas J. Lenoci, Maryanne Rothlind, Johannes Henn-Haase, Clare Choucroun, Gerard Weiner, Michael W. Marmar, Charles R. TI Neuropsychological functioning in posttraumatic stress disorder and alcohol abuse SO NEUROPSYCHOLOGY LA English DT Article DE PTSD; veterans; memory; attention; alcohol abuse ID REDUCED HIPPOCAMPAL VOLUME; CHILDHOOD SEXUAL-ABUSE; EXPLICIT MEMORY; COMBAT VETERANS; PTSD; ATTENTION; DEFICITS; DYSFUNCTION; RECOVERY; VICTIMS AB Studies have shown differences in neuropsychological functioning between groups with posttraumatic stress disorder (PTSD) and control participants. Because individuals with PTSD often have a history of comorbid alcohol abuse, the extent to which an alcohol confound is responsible for these differences remains a concern. The current study compares neuropsychological testing scores in 4 groups of veterans with and without PTSD (PTSD+ and PTSD-, respectively) and with and without a history of alcohol abuse (ETOH+ and ETOH-, respectively): n for PTSD+/ETOH+ = 30, n for PTSD+/ETOH- = 37, n for PTSD-/ETOH+ = 30, and n for PTSD-/ETOH- = 31. Results showed that PTSD, when alcohol. educational level, vocabulary, and depression are controlled for, was associated with decreased verbal memory, attention, and processing speed performance. Alcohol abuse history was associated with decreased visual memory performance. By controlling for alcohol and depression, the authors can more conclusively demonstrate that verbal memory and attention differences are associated with PTSD. C1 San Francisco Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. San Franciscos Vet Affairs Med Ctr, Dept Radiol, San Francisco, CA USA. RP Samuelson, KW (reprint author), Alliant Int Univ, Calif Sch Profess Psychol, 1 Beach St,Suite 100, San Francisco, CA USA. EM ksamuelson@alliant.edu FU NIA NIH HHS [P01 AG019724, P01 AG019724-050002] NR 55 TC 62 Z9 63 U1 4 U2 11 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD NOV PY 2006 VL 20 IS 6 BP 716 EP 726 DI 10.1037/0894-4105.20.6.716 PG 11 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 101SO UT WOS:000241761000010 PM 17100516 ER PT J AU Ogilvy, CS Cheung, AC Mitha, AP Hoh, BL Carter, BS AF Ogilvy, Christopher S. Cheung, Arnold C. Mitha, Alim P. Hoh, Brian L. Carter, Bob S. TI Outcomes for surgical and endovascular management of intracranial aneurysms using a comprehensive grading system SO NEUROSURGERY LA English DT Article DE intracranial aneurysm; outcome studies; subarachnoid hemorrhage ID TRIAL ISAT; SURGERY; INTERVENTION; COILING; RISKS AB OBJECTIVE: A systematic approach to the consideration of various factors on outcome demands a comprehensive grading system for patients with intracranial aneurysms. We have previously identified potential patient- and lesion-specific factors that correlate strongly with outcome after treatment for intracranial aneurysms, and we have developed a comprehensive grading system based on these factors. In this study, we evaluate this grading system in a large series of aneurysm patients treated by surgery and endovascular therapy. METHODS: Between January 1998 and January 2003, ruptured and unruptured aneurysm patients were prospectively entered into a database. Based on our previous study that showed which factors correlated strongly with outcome, data were collected on patient age, aneurysm size, Hunt and Hess grade, and Fisher scale (if presenting with subarachnoid hemorrhage), and a Massachusetts General Hospital grade was then applied. The modified Glasgow Outcome Scale was used for clinical assessment at follow-up, and a binary analysis classified patients into favorable versus unfavorable outcome. Univariate and multivariate analyses for the predictor variables, were performed. RESULTS: One thousand forty-nine aneurysms in 914 patients were identified. Fifty-eight percent (n = 608) of the lesions were unruptured, and 25% (n = 261) were treated endovascularly. For patients treated either surgically or endovascularly, worsening outcome was demonstrated for higher Hunt and Hess grade (surgery, P < 0.001; endovascular, P < 0.001), Fisher scale (surgery, P < 0.001; endovascular, P < 0.001) and for older patients (surgery, P < 0.001; endovascular, P = 0.004). Size of aneurysm had a significant effect on outcome after surgery (P = 0.04), but not after endovascular therapy (P = 0.3). Overall, there was a greater proportion of favorable outcomes for anterior circulation compared with posterior circulation lesions (P < 0.0001). For both the surgical and endovascular subgroups, NIGH grade correlated well with clinical outcomes. CONCLUSION: The MGH grade is a comprehensive grading system that is easily applied and that allows separation of patients with aneurysms into groups with markedly different outcomes. This information can potentially be helpful in making treatment decisions and when discussing projected outcome before surgical or endovascular intervention of both unruptured and ruptured aneurysms. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Univ Florida, Dept Neurosurg, Gainesville, FL 32611 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,VBK 710, Boston, MA 02114 USA. EM cogilvy@partners.org NR 10 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 2006 VL 59 IS 5 BP 1037 EP 1042 DI 10.1227/01.NEU.0000246579.51572.6D PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 128GI UT WOS:000243645800015 PM 17143238 ER PT J AU Swan, BA Conway-Phillips, R Griffin, KF AF Swan, Beth Ann Conway-Phillips, Regina Griffin, Karen F. TI Demonstrating the value of the RN in ambulatory care SO NURSING ECONOMICS LA English DT Editorial Material ID STAFF NURSE ROLE; PATIENT SATISFACTION; DIABETES CARE; DIMENSIONS; TELEPHONE; COMMUNITY; OUTCOMES; MANAGEMENT; CENTERS; LESSONS AB center dot During 2003, an estimated 906 million visits were made to physician offices in the United States (Hing, Cherry, & Woodwell, 2005). center dot Overall, 42% of visits to outpatient settings were attended by a registered nurse (Middleton & Hing, 2005). center dot Despite ambulatory care being the fastest growing site for care, it is the least studied. center dot The purpose of this article is to provide an overview of the role of the RN in ambulatory care and describe the direct and indirect economic value of RNs in ambulatory care settings. C1 Thomas Jefferson Univ, Grad Program, Jefferson Sch Nursing, Jefferson Coll Hlth Profess, Philadelphia, PA 19107 USA. Humana Inc, Delegat Compliance, Louisville, KY USA. S Texas Vet Hlth Care Syst, Grand Prairie, TX USA. RP Swan, BA (reprint author), Thomas Jefferson Univ, Grad Program, Jefferson Sch Nursing, Jefferson Coll Hlth Profess, Philadelphia, PA 19107 USA. NR 58 TC 12 Z9 12 U1 0 U2 2 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD NOV-DEC PY 2006 VL 24 IS 6 BP 315 EP 322 PG 8 WC Nursing SC Nursing GA 121SH UT WOS:000243176800006 PM 17266008 ER PT J AU David, G Dannenberg, JH Simpson, N Finnerty, PM Miao, L Turner, GM Ding, Z Carrasco, R DePinho, RA AF David, G. Dannenberg, J. -H. Simpson, N. Finnerty, P. M. Miao, L. Turner, G. M. Ding, Z. Carrasco, R. DePinho, R. A. TI Haploinsufficiency of the mSds3 chromatin regulator promotes chromosomal instability and cancer only upon complete neutralization of p53 SO ONCOGENE LA English DT Article DE mSin3; chromatin; histone deacetylase; mouse model; aneuploidy; p53 ID PERICENTRIC HETEROCHROMATIN; DEACETYLASE COMPLEX; COREPRESSOR COMPLEX; INTEGRAL COMPONENT; MAMMALIAN-CELLS; ACETYLATION; SUPPRESSOR; GROWTH; MICE; CARCINOGENESIS AB The mSin3 corepressor complex has been linked to diverse cancer signaling pathways through its capacity to regulate target gene expression via chromatin modification. mSds3, a cell essential gene, is a key component of the mSin3 complex serving to maintain its inherent histone deacetylase activity. mSds3 also serves an essential role in the establishment of pericentric heterochromatin, and genetic ablation of mSds3 results in chromosome mis-segregation. In contrast, mSin3A nullizygous cells show normal chromosome dynamics and cytogenetic profiles. The integral role of mSds3 in controlling chromosome segregation and mSin3-regulated transcriptional networks prompted efforts to determine the neoplastic impact of loss of one copy of mSds3 or mSin3A. In particular, we assessed whether loss of one copy of mSds3, alone or in combination with p53 mutation, results in aneuploidy and promotes a cancer-prone condition in the mouse. We observe that, in a p53 null background, loss of one mSds3 allele results in accelerated tumor onset and increased tumor burden. Notably, these mSds3(+/-) p53(-/-) tumors exhibit a more complex cytogenetic profile characterized by marked aneuploidy and centromeric associations. The presence of even one copy of p53 is sufficient to suppress the accelerated tumorigenesis in mSds3(+/-) mice, consistent with a key role for p53 in monitoring mitotic fidelity. These observations with Sds3 mutant mice contrast with mSin3A(+/-) p53(-/-) mice, which do not show an accelerated or increased tumor incidence relative to mSin3A(+/+) p53(-/-) controls, correlating with the absence of aneuploidy detected upon mSin3A genetic inactivation. This genetic study establishes that the capacity of mSds3 to cooperate with p53 deficiency in cancer predisposition relates to its specific role in chromosome segregation, rather than its central role in maintaining a functional mSin3A complex. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NYU, Sch Med, Dept Pharmacol, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 413, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu OI , gregory/0000-0002-3371-4558 FU NCI NIH HHS [R01CA86379] NR 26 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2006 VL 25 IS 56 BP 7354 EP 7360 DI 10.1038/sj.onc.1209734 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 110ZE UT WOS:000242419100004 PM 16767157 ER PT J AU Fonteyn, M McDonough, K Salazar, R Bauer-Wu, S AF Fonteyn, Marsha McDonough, Katherine Salazar, Romelia Bauer-Wu, Susan TI Support for frontline oncology nurses' and administrators' scholarly activities SO ONCOLOGY NURSING FORUM LA English DT Editorial Material C1 Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. McDonough Grp, Norwood, MA USA. Univ Massachusetts, Grad Sch Nursing, Worcester, MA 01605 USA. RP Fonteyn, M (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. EM marsha_fonteyn@dfci.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2006 VL 33 IS 6 BP 1061 EP 1063 DI 10.1188/06.ONF.1061-1063 PG 3 WC Oncology; Nursing SC Oncology; Nursing GA 103OZ UT WOS:000241897900005 PM 17152655 ER PT J AU Sarna, L Cooley, ME Brown, JK Williams, RD Chernecky, C Padilla, G Danao, LL AF Sarna, Linda Cooley, Mary E. Brown, Jean K. Williams, Roma D. Chernecky, Cynthia Padilla, Geraldine Danao, Leda Layo TI Quality of life and health status of dyads of women with lung cancer and family members SO ONCOLOGY NURSING FORUM LA English DT Article ID PSYCHOLOGICAL DISTRESS; SCREENING INSTRUMENT; FUNCTIONAL-STATES; LONGITUDINAL VIEW; PATIENTS SYMPTOMS; CAREGIVERS; DEPRESSION; SURVIVORS; IMPACT; VALIDATION AB Purpose/Objectives: To describe and compare the quality of life (QOL) and health status of dyads of women with lung cancer and their family members and to explore the correlates of family members' QOL. Research Approach: Descriptive, cross-sectional. Setting: Interview, self-report. Participants: 51 dyads consisting of women with lung cancer and their family members. Methodologic Approach: One-time assessment of family members' and patients' QOL, health status, and demographics and patients' clinical characteristics. Main Research Variables: Family and patient QOL and health status. Findings: QOL of the dyads was not significantly related. Poorer physical QOL of family members was associated with older age, comorbid conditions, less education, and alcohol use. Poorer emotional QOL of family members was associated with younger age, depressed mood, and not being a spouse. Fifty-nine percent of family members had comorbid conditions. Significantly more family members continued to smoke and use alcohol. Conclusions: The QOL of family members of patients with lung cancer is diminished when their own health status is compromised. Further study is needed. Interpretation: Additional study is needed to identify family members at risk for diminished QOL and with compromised health status because these factors might affect ability to support patients with lung cancer. C1 Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA. Univ Alabama, Sch Nursing, Birmingham, AL USA. Med Coll Georgia, Sch Nursing, Augusta, GA 30912 USA. Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Sarna, L (reprint author), Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. EM lsarna@ucla.edu NR 55 TC 22 Z9 22 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2006 VL 33 IS 6 BP 1109 EP 1116 DI 10.1188/06.ONF.1109-1116 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 103OZ UT WOS:000241897900010 PM 17149394 ER PT J AU Subramanian, ML Heier, JS Esrick, E Devaiah, AK Topping, TM Frederick, AK Morley, MG AF Subramanian, Manju L. Heier, Jeffrey S. Esrick, Erica Devaiah, Anand K. Topping, Trexler M. Frederick, Albert K. Morley, Micbael G. TI Preoperative visual acuity as a prognostic indicator for laser treatment of macular edema due to branch retinal vein occlusion SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol ID ADVENTITIAL SHEATHOTOMY; DECOMPRESSION AB m BACKGROUND AND OBJECTIVE: To determine the visual outcome of laser treatments for macular edema due to branch retinal vein occlusion (BRVO) in patients with a preoperative visual acuity (VA) of 20/200 or worse compared to patients with a preoperative VA of better than 20/200. PATIENTS AND METHODS: Records of 88 patients with macular edema secondary to BRVO undergoing laser treatment from 1984 to 2003 were reviewed. Mean VA was measured before and after each treatment and after the final treatment. RESULTS: All patients received between one and five laser treatments. Preoperative VA was better than 20/200 in 56 patients (group 1) and 20/200 or worse in 32 patients (group 2). Patients in group I had a mean improvement of 0.48 lines and 57% had a final VA of 20/40 or better. Patients in group 2 had a mean improvement of 1.69 lines and 20% had a final VA of 20/40 or better. CONCLUSIONS: Patients with poor VA (20/200 or worse) secondary to macular edema due to BRVO responded positively to laser treatment. The level of preoperative VA can be a useful predictor of visual outcome. These patients should consider laser treatment before alternative, more aggressive approaches. C1 Ophthalm Consultans Boston, Boston, MA USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Subramanian, ML (reprint author), 85 E Concord St,8th Floor, Boston, MA 02118 USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD NOV-DEC PY 2006 VL 37 IS 6 BP 462 EP 467 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 107VD UT WOS:000242198200003 PM 17152539 ER PT J AU Zambarakji, HJ Lane, AM Ezra, E Gauthier, D Goitein, M Adams, JA Munzenrider, JE Miller, JW Gragoudas, ES AF Zambarakji, Hadi J. Lane, Anne Marie Ezra, Eric Gauthier, Danny Goitein, Michael Adams, Judy A. Munzenrider, John E. Miller, Joan W. Gragoudas, Evangelos S. TI Proton beam irradiation for neovascular age-related macular degeneration SO OPHTHALMOLOGY LA English DT Article ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; RANDOMIZED CLINICAL-TRIAL; RADIATION-THERAPY; PHOTODYNAMIC THERAPY; VERTEPORFIN THERAPY; VISUAL-ACUITY; RADIOTHERAPY; TELETHERAPY; MEMBRANES; SECONDARY AB Objective: To evaluate safety and visual outcomes after proton therapy for subfoveal neovascular age-related macular degeneration (AMD). Design: Randomized dose-ranging clinical trial. Participants: One hundred sixty-six patients with angiographic evidence of classic choroidal neovascularization resulting from AMD and best-corrected visual acuity of 20/320 or better. Methods: Patients were assigned randomly (1:1) to receive 16-cobalt gray equivalent (CGE) or 24-CGE proton radiation in 2 equal fractions. Visual acuity was measured using standardized protocol refraction. Complete ophthalmological examinations, color fundus photography, and fluorescein angiography were performed before and 3, 6, 12, 18, and 24 months after treatment. Main Outcome Measure: Proportion of eyes losing 3 or more lines of vision from baseline. Kaplan-Meier statistics were used to compare cumulative rates of vision loss between the 2 treatment groups. Results: At 12 months after treatment, 36 eyes (42%) and 27 eyes (35%) lost 3 or more lines of vision in the 16-CGE and 24-CGE groups, respectively. Rates increased to 62% in the 16-CGE group and 53% in the 24-CGE group by 24 months after treatment (P=0.40). Radiation complications developed in 15.7% of patients receiving 16 CGE and 14.8% of patients receiving 24 CGE. Conclusions: No significant differences in rates of visual loss were found between the 2 dose groups. Proton radiation may be useful as an adjuvant therapy or as an alternative for patients who decline or are not appropriate for approved therapies. (c) 2006 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Gragoudas, ES (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Evangelos_Gragoudas@meei.harvard.edu NR 34 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2006 VL 113 IS 11 BP 2012 EP 2019 DI 10.1016/j.ophtha.2006.05.036 PG 8 WC Ophthalmology SC Ophthalmology GA 101CS UT WOS:000241717100015 PM 16935343 ER PT J AU Yu, CC Lau, C Tunnell, JW Hunter, M Kalashnikov, M Fang-Yen, C AF Yu, Chung-Chieh Lau, Condon Tunnell, James W. Hunter, Martin Kalashnikov, Maxim Fang-Yen, Christopher TI Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy SO OPTICS LETTERS LA English DT Article ID SIZE DISTRIBUTION; INTACT-CELLS; TISSUE AB We describe azimuthal light scattering spectroscopy (phi/LSS), a novel technique for assessing epithelial-cell nuclear morphology. The difference between the spectra measured at azimuthal angles phi=0 degrees and phi=90 degrees preferentially isolates the single backscattering contribution due to large (similar to 10 mu m) structures such as epithelial cell nuclei by discriminating against scattering from smaller organelles and diffusive background. We demonstrate the feasibility of using phi/LSS for cancer detection by showing that spectra from cancerous colon tissue exhibit significantly greater azimuthal asymmetry than spectra from normal colonic tissues. (c) 2006 Optical Society of America. C1 MIT, GR Harrison Spect Lab, Cambridge, MA 02139 USA. Newton Labs Inc, Woburn, MA 01801 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. MIT, Laser Biomed Res Ctr, Cambridge, MA 02139 USA. RP Yu, CC (reprint author), MIT, GR Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM chungyu@mit.edu OI LAU, Condon/0000-0002-6569-5814; Fang-Yen, Christopher/0000-0002-4568-3218 FU NCI NIH HHS [R01-CA97966]; NCRR NIH HHS [P41-RR02594] NR 9 TC 21 Z9 21 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD NOV 1 PY 2006 VL 31 IS 21 BP 3119 EP 3121 DI 10.1364/OL.31.003119 PG 3 WC Optics SC Optics GA 097PV UT WOS:000241461300015 PM 17041654 ER PT J AU Giannini, PJ Shetty, KV Horan, SL Reid, WD Lichmore, LL AF Giannini, Peter J. Shetty, Kishore V. Horan, Sara L. Reid, Wayne D. Lichmore, Loven L. TI Adenoid cystic carcinoma of the buccal vestibule: A case report and review of the literature SO ORAL ONCOLOGY LA English DT Article DE carcinoma; adenoid cystic; buccal; vestibule ID MINOR SALIVARY-GLANDS; NECK; HEAD AB Minor salivary gland tumors of the buccal vestibule are relatively rare. Adenoid cystic carcinoma is the fifth most common salivary gland malignancy following mucoepidermoid carcinoma, adenocarcinoma not otherwise specified (NOS), acinic cell adenocarcinoma and polymorphous low-grade adenocarcinoma (PLGA). Greater than half of adenoid cystic carcinomas occur in the parotid and submandibular glands. The most common intraoral site is the patate. Adenoid cystic carcinoma tends to have a protracted clinical course with wide infiltration and late distant metastases. We present a case of an adenoid cystic carcinoma of the buccal vestibule in a 59-year-old Caucasian female patient that she had been aware of for 15 years. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Nebraska, Ctr Med, Coll Dent, Lincoln, NE 68583 USA. Univ Texas, Dent Branch, Houston, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Sch Dent, Aurora, CO USA. Temple Univ, Sch Dent, Philadelphia, PA 19122 USA. RP Giannini, PJ (reprint author), Univ Nebraska, Ctr Med, Coll Dent, 40th & Holdrege St,Box 830740, Lincoln, NE 68583 USA. EM pgiannini@unmc.edu NR 21 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD NOV PY 2006 VL 42 IS 10 BP 1029 EP 1032 DI 10.1016/j.oraloncology.2006.06.005 PG 4 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 108TW UT WOS:000242263100012 PM 16996786 ER PT J AU Hart, ES Luther, B Grottkau, BE AF Hart, Erin S. Luther, Brenda Grottkau, Brian E. TI Broken bones: Common pediatric lower extremity fractures - Part III SO ORTHOPAEDIC NURSING LA English DT Article ID FEMORAL-SHAFT FRACTURES; SUPERIOR ILIAC SPINE; EXTERNAL FIXATION; AVASCULAR NECROSIS; NECK FRACTURES; COMPARTMENT SYNDROME; AVULSION FRACTURES; FEMUR FRACTURES; TIBIA FRACTURES; YOUNG-CHILDREN C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, Boston, MA USA. RP Hart, ES (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, Boston, MA USA. NR 68 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0744-6020 J9 ORTHOP NURS JI Orthop. Nurs. PD NOV-DEC PY 2006 VL 25 IS 6 BP 390 EP 407 PG 18 WC Nursing; Orthopedics SC Nursing; Orthopedics GA 110PQ UT WOS:000242391300008 PM 17130761 ER PT J AU Meltzer, EO Hamilos, DL Hadley, JA Lanza, DC Marple, BF Nicklas, RA Adinoff, AD Bachert, C Borish, L Chinchilli, VM Danzig, MR Ferguson, BJ Fokkens, WJ Jenkins, SG Lund, VJ Mafee, MF Naclerio, RM Pawankar, R Ponikau, JU Schubert, MS Slavin, RG Stewart, MG Togias, A Wald, ER Winther, B AF Meltzer, Eli O. Hamilos, Daniel L. Hadley, James A. Lanza, Donald C. Marple, Bradley F. Nicklas, Richard A. Adinoff, Allen D. Bachert, Claus Borish, Larry Chinchilli, Vernon M. Danzig, Melvyn R. Ferguson, Berrylin J. Fokkens, Wytske J. Jenkins, Stephen G. Lund, Valerie J. Mafee, Mahmood F. Naclerio, Robert M. Pawankar, Ruby Ponikau, Jens U. Schubert, Mark S. Slavin, Raymond G. Stewart, Michael G. Togias, Alkis Wald, Ellen R. Winther, Birgit TI Rhinosinusitis: Developing guidance for clinical trials SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review ID ALLERGIC FUNGAL SINUSITIS; FUROATE NASAL SPRAY; ACUTE BACTERIAL RHINOSINUSITIS; QUALITY-OF-LIFE; COMPUTED TOMOGRAPHIC FINDINGS; RANDOMIZED CONTROLLED-TRIAL; UBIQUITOUS AIRBORNE FUNGI; ORAL ANTIBIOTIC-THERAPY; NEWLY RECOGNIZED FORM; MAXILLARY SINUSITIS AB The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication, "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) rardiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods. (C) 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. All rights reserved. C1 Univ Colorado, Dept Pediat & Pharmacol, Denver, CO 80202 USA. Univ Hosp, ENT Clin, Ghent, Belgium. Univ Virginia Hlth Syst, Dept Med, Asthma & Allerg Dis Ctr, Charlottesville, VA USA. Penn State Coll Med, Dept Hlth Evaluat Sci, Hershey, PA USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol, Div Sinonasal Disorder & Allergy, Pittsburgh, PA USA. Univ Amsterdam, Acad Med Ctr Hosp, ENT Dept, Amsterdam, Netherlands. Univ Rochester, Med Ctr, Dept Otolaryngol, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Mt Sinai Med Ctr, Clin Microbiol Labs, New York, NY 10029 USA. Sinus & Nasal Inst Florida PA, St Anthonys Carillon Outpatient & Wellness Ctr, St Petersburg, FL USA. UCL, Dept Rhinol, London, England. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. Univ Texas, SW Med Ctr, Dept Otolaryngol, Dallas, TX USA. Univ Calif San Diego, Allergy & Asthma Med Grp & Res Ctr, Dept Pediat, San Diego, CA 92123 USA. Univ Chicago, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Nippon Med Coll, Tokyo 113, Japan. SUNY Buffalo, Buffalo, NY 14260 USA. Univ Arizona, Dept Med, Phoenix, AZ USA. Allergy Asthma Clin LTD, Phoenix, AZ USA. St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO USA. Weill Cornell Med Coll, Dept Otolaryngol, New York, NY USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA. Univ Virginia Hlth Syst, Dept Otolaryngol, Charlottesville, VA USA. RP Meltzer, EO (reprint author), Univ Calif San Diego, Allergy & Asthma Med Grp & Res Ctr, Dept Pediat, 9610 Granite Ridge Dr,Suite B, San Diego, CA 92123 USA. EM eomeltzer@aol.com NR 144 TC 55 Z9 56 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2006 VL 135 IS 5 SU S BP S31 EP S80 DI 10.1016/j.otohns.2006.09.014 PG 50 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 105ID UT WOS:000242022700001 PM 17081855 ER PT J AU Ballantyne, JC AF Ballantyne, Jane C. TI Opioids for chronic pain: Taking stock SO PAIN LA English DT Editorial Material C1 Massachusetts Gen Hosp, MGH Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 01810 USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, MGH Pain Ctr, Dept Anesthesia & Crit Care, 50 Staniford St, Boston, MA 01810 USA. EM jballantyne@partners.org NR 7 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2006 VL 125 IS 1-2 BP 3 EP 4 DI 10.1016/j.pain.2006.07.005 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 101AZ UT WOS:000241712600002 PM 16934403 ER PT J AU Gallagher, RM AF Gallagher, Rollin M. TI Pain intensity, emotional state, and personality trait: Which comes first? SO PAIN MEDICINE LA English DT Editorial Material ID WADDELL SIGNS C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 9 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV-DEC PY 2006 VL 7 IS 6 BP 471 EP 472 DI 10.1111/j.1526-4637.2006.00245.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 118JU UT WOS:000242939400001 PM 17112358 ER PT J AU Alsina, J Stirman, A Mino-Kenudson, M Fernandez-del Castillo, C Warshaw, A Thayer, SP AF Alsina, J. Stirman, A. Mino-Kenudson, M. Fernandez-del Castillo, C. Warshaw, A. Thayer, S. P. TI SHH misexpression in the adult pancreas results in the expansion of both a mucinous ductal metaplasia and a fibrosing mesenchyme SO PANCREAS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2006 VL 33 IS 4 BP 443 EP 443 DI 10.1097/00006676-200611000-00029 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101BS UT WOS:000241714500029 ER PT J AU Garatea, R Targarona, J Barreda, L Warshaw, A del Castillo, CF AF Garatea, R. Targarona, J. Barreda, L. Warshaw, A. del Castillo, C. Fernandez TI Solid pseudopapillary neoplasm of the pancreas: Report of 31 resected cases and description of a paradoxical inverse relation between age and tumor size SO PANCREAS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Hosp Edgardo Rebagliati Martins, Lima, Peru. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2006 VL 33 IS 4 BP 463 EP 463 DI 10.1097/00006676-200611000-00092 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101BS UT WOS:000241714500092 ER PT J AU Keck, T Rodriguez, R Marjanovic, G Razo, AO Adam, U Fernandez-del Castillo, C Hopt, UT Warshaw, AL AF Keck, T. Rodriguez, R. Marjanovic, G. Razo, A. O. Adam, U. Fernandez-del Castillo, C. Hopt, U. T. Warshaw, A. L. TI Transatlantic differences in the surgical treatment of chronic pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 Univ Freiburg, Dept Gen & Visceral Surg, Freiburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2006 VL 33 IS 4 BP 473 EP 473 DI 10.1097/00006676-200611000-00125 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101BS UT WOS:000241714500125 ER PT J AU Mareninova, OA Lugea, A Odinokova, IV Tsukamoto, H Gukovsky, I Pandol, SJ Gukovskaya, AS AF Mareninova, O. A. Lugea, A. Odinokova, I. V. Tsukamoto, H. Gukovsky, I. Pandol, S. J. Gukovskaya, A. S. TI Akt activation in alcoholic pancreatitis: Role of PTEN SO PANCREAS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 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 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2006 VL 33 IS 4 BP 481 EP 481 DI 10.1097/00006676-200611000-00150 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101BS UT WOS:000241714500150 ER PT J AU Rodriguez, JR Salvia, R Crippa, S Bassi, C Pederzoli, P Capelli, P Lauwers, G Mino-Kenudson, M McGrath, D Razo, O Thayer, SP Warshaw, AL Fernandez-del Castillo, C AF Rodriguez, J. R. Salvia, R. Crippa, S. Bassi, C. Pederzoli, P. Capelli, P. Lauwers, G. Mino-Kenudson, M. McGrath, D. Razo, O. Thayer, S. P. Warshaw, A. L. Fernandez-del Castillo, C. TI Branch duct intraductal papillary mucinous neoplasms of the pancreas (IPMNs): Confirmed findings in 145 resected patients SO PANCREAS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Verona, Dept Surg, I-37100 Verona, Italy. Univ Verona, Dept Pathol, I-37100 Verona, Italy. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2006 VL 33 IS 4 BP 493 EP 493 DI 10.1097/00006676-200611000-00191 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101BS UT WOS:000241714500191 ER PT J AU Vagefi, PA Razo, O Deshpande, V McGrath, DJ Lauwers, GY Thayer, SP Warshaw, AL Fernandez-Del Castillo, C AF Vagefi, P. A. Razo, O. Deshpande, V. McGrath, D. J. Lauwers, G. Y. Thayer, S. P. Warshaw, A. L. Fernandez-Del Castillo, C. TI Evolving patterns in the detection of pancreatic neuroendocrine tumors (PNETs): The Massachusetts general hospital experience SO PANCREAS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2006 VL 33 IS 4 BP 504 EP 504 DI 10.1097/00006676-200611000-00227 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101BS UT WOS:000241714500227 ER PT J AU Chantada, G Doz, F Antoneli, CBG Grundy, R Stannard, FFC Dunkel, IJ Grabowski, E Leal-Leal, C Rodriguez-Galindo, C Schvartzman, E Popovic, MB Kremens, B Meadows, AT Zucker, JM AF Chantada, Guillermo Doz, Francois Antoneli, Celia B. G. Grundy, Richard Stannard, F. F. Clare Dunkel, Ira J. Grabowski, Eric Leal-Leal, Carlos Rodriguez-Galindo, Carlos Schvartzman, Enrique Popovic, Maja Beck Kremens, Bernhard Meadows, Anna T. Zucker, Jean-Michel TI A proposal for an international retinoblastoma staging system SO PEDIATRIC BLOOD & CANCER LA English DT Article DE classification; extra-ocular; metastasis; retinoblastoma; staging ID HIGH-RISK RETINOBLASTOMA; UNILATERAL RETINOBLASTOMA; SINGLE INSTITUTION; CHEMOTHERAPY AB Background. Although intra-retinal tumor has long been staged presurgically according to the Reese-Ellsworth (R-E) system, retinoblastoma differs from other pediatric neoplasms in never having had a widely accepted classification system that encompasses the entire spectrum of the disease. Comparisons among studies that consider disease extension, risk factors for extra-ocular relapse, and response to therapy require a universally accepted staging system for extra-ocular disease. Procedure. A committee of retinoblastoma experts from large centers worldwide has developed a consensus classification that can encompass all retinoblastoma cases and is presented herein. Patients are classified according to extent of disease and the presence of overt extra-ocular extension. In addition, a proposal for substaging considering histopathological features of enucleated specimens is presented to further discriminate between Stage I and 11 patients. Results. The following is a summary of the classification system developed-Stage 0: Patients treated conservatively (subject to presurgical ophthalmologic classifications); Stage 1: Eye enucleated, completely resected histologically; Stage II: Eye enucleated, microscopic residual tumor; Stage III: Regional extension [(a) overt orbital disease, (b) preauricularor cervical lymph node extension]; Stage IV: Metastatic disease [(a) hematogenous metastasis: (1) single lesion, (2) multiple lesions; (b) CNS extension: (1) prechiasmatic lesion, (2) CNS mass, (3) leptomeningeal disease]. A proposal is also presented for substaging of enucleated Stages I and 11 eyes. Conclusions. The proposed staging system is the product of an international effort to adopt a uniform staging system for patients with retinoblastoma to cover the whole spectrum of the disease. C1 Hosp JP Garrahan, Dept Hematol Oncol, RA-1245 Buenos Aires, DF, Argentina. Inst Curie, Paris, France. Hosp AC Camargo Fund Antonio Prudente, Dept Pediat Oncol, Sao Paulo, Brazil. Birnimgham Childrens Hosp, Dept Pediat Oncol, Birmingham, W Midlands, England. Univ Cape Town, ZA-7925 Cape Town, South Africa. Groote Schuur Hosp, Dept Radiat Oncol, ZA-7925 Cape Town, South Africa. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Inst Nacl Pediat, Mexico City, DF, Mexico. St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. CHU Vaudois, Dept Pediat Hematooncol, CH-1011 Lausanne, Switzerland. Univ Essen Gesamthsch, Dept Pediat Oncol, D-4300 Essen 1, Germany. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. RP Chantada, G (reprint author), Hosp JP Garrahan, Dept Hematol Oncol, Combate Pozos 1881, RA-1245 Buenos Aires, DF, Argentina. EM gchantada@garraha.gov.ar RI Antoneli, Celia/P-5133-2015; OI Antoneli, Celia/0000-0003-1106-9751; Dunkel, Ira/0000-0001-8091-6067 NR 25 TC 71 Z9 74 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2006 VL 47 IS 6 BP 801 EP 805 DI 10.1002/pbc.20606 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 091CR UT WOS:000241004200009 PM 16358310 ER PT J AU Hudson, LA Bernard, TJ Tseng, BS Miller, BR Corboy, JR AF Hudson, Lynsee A. Bernard, Timothy J. Tseng, Brian S. Miller, Bradford R. Corboy, John R. TI Neuromyelitis optica immunoglobulin G in a child SO PEDIATRIC NEUROLOGY LA English DT Article DE - ID MULTIPLE-SCLEROSIS; MARKER AB Neuromyelitis optica or Devic's syndrome is an uncommon demyelinating disorder that preferentially attacks the spinal cord and optic nerves. Although it is well described in adults, childhood neuromyelitis optica has rarely been reported in the literature and is frequently misdiagnosed as severe multiple sclerosis. Recently, a serum immunoglobulin G test for neuromyelitis optica has become available which may clarify and accelerate the diagnosis. This report describes a child with recurrent myelitis and an elongated spinal cord lesion who was found to have positive neuromyelitis optica autoantibody. We believe that neuromyelitis optica autoantibody testing should be performed in cases of pediatric transverse myelitis with multiple vertical segments or recurrence. (c) 2006 by Elsevier Inc. All rights reserved. C1 Univ Colorado & Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Childrens Hosp, Dept Neurol, Denver, CO 80218 USA. Childrens Hosp, Dept Pediat, Denver, CO 80218 USA. Childrens Hosp, Dept Cell & Dev Biol, Denver, CO 80218 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Corboy, JR (reprint author), Univ Colorado & Hlth Sci Ctr, Dept Neurol, 4200 E 9th Ave B183, Denver, CO 80262 USA. EM john.corboy@uchsc.edu FU NIAMS NIH HHS [K08 AR052308-04] NR 11 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD NOV PY 2006 VL 35 IS 5 BP 370 EP 372 DI 10.1016/j.pediatrneurol.2006.06.008 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 105ND UT WOS:000242036100015 PM 17074612 ER PT J AU Hait, E Liang, M Degar, B Glickman, J Fox, VL AF Hait, Elizabeth Liang, Marilyn Degar, Barbara Glickman, Jonathan Fox, Victor L. TI Gastrointestinal tract involvement in Langerhans cell histiocytosis: Case report and literature review SO PEDIATRICS LA English DT Article DE Langerhans cells histiocytosis; colitis AB Digestive tract involvement in Langerhans cell histiocytosis is exceedingly rare. We report a case of Langerhans cell histiocytosis in an otherwise thriving neonate presenting with hematochezia, anemia, and rash. We also review the few cases of Langerhans cell histiocytosis with gastrointestinal involvement reported in the English-language medical literature. Although gastrointestinal involvement can range in severity from mild to life-threatening, its presence may be indicative of multisystemic disease, and aggressive treatment should be considered. C1 Childrens Hosp, Div Gastroenterol & Nutr, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Dermatol, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Hematol & Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fox, VL (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, Dana Farber Canc Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM victor.fox@childrens.harvard.edu NR 17 TC 17 Z9 18 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2006 VL 118 IS 5 BP E1593 EP E1599 DI 10.1542/peds.2006-0708 PG 7 WC Pediatrics SC Pediatrics GA 101HK UT WOS:000241731700116 PM 17030599 ER PT J AU Braaten, EB Norman, D AF Braaten, Ellen B. Norman, Dennis TI Intelligence (IQ) testing SO PEDIATRICS IN REVIEW LA English DT Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Braaten, EB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 14 TC 4 Z9 4 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD NOV PY 2006 VL 27 IS 11 BP 403 EP 407 PG 5 WC Pediatrics SC Pediatrics GA 107MX UT WOS:000242176800001 PM 17079505 ER PT J AU Gourcerol, G Million, M Adelson, DW Wang, Y Wang, L Rivier, J St-Pierre, DH Tache, Y AF Gourcerol, G. Million, M. Adelson, D. W. Wang, Y. Wang, L. Rivier, J. St-Pierre, D. H. Tache, Y. TI Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents SO PEPTIDES LA English DT Article DE CCK; obestatin; food intake; gastric emptying; gastric relaxation; gastric vagal afferent ID FOOD-INTAKE; SYNERGISTIC INTERACTION; OBESE MICE; LEAN MICE; CHOLECYSTOKININ; GHRELIN; LEPTIN; RATS; SENSITIVITY; RECEPTORS AB Obestatin is a new peptide for which anorexigenic effects were recently reported in mice. We investigate whether peripheral injection of obestatin or co-injection with cholecystokinin (CCK) can modulate food intake, gastric motor function (intragastric pressure and emptying) and gastric vagal afferent activity in rodents. Obestatin (30, 100 and 300 mu g/kg, i.p.) did not influence cumulative food intake for the 2 h post-injection in rats or mice nor gastric emptying in rats. In rats, obestatin (300 mu g/kg) did not modify CCK (1 mu g/kg, i.p.)induced significant decrease in food intake (36.6%) and gastric emptying (31.0%). Furthermore, while rats injected with CCK (0.3 mu g/kg, i.v.) displayed gastric relaxation, no change in gastric intraluminal pressure was elicited by obestatin (300 mu g/kg, i.v.) pre- or post-CCK administration. In in vitro rat gastric vagal afferent preparations, 20 units that had nonsignificant changes in basal activity after obestatin at 30 mu g responded to CCK at 10 ng by a 182% increase. These data show that obestatin neither influences cumulative food intake, gastric motility or vagal afferent activity nor CCK-induced satiety signaling (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, VA Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. Univ Montreal, Fac Med, Dept Nutr, Montreal, PQ H3C 3J7, Canada. RP Tache, Y (reprint author), Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, VA Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, CURE Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu OI Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [DK-41301, DK-26741, R01 DK-33061] NR 36 TC 92 Z9 96 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2006 VL 27 IS 11 BP 2811 EP 2819 DI 10.1016/j.peptides.2006.07.012 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 109OW UT WOS:000242318900035 PM 16934368 ER PT J AU Pekary, AE Stevens, SA Sattin, A AF Pekary, A. E. Stevens, S. A. Sattin, A. TI Valproate and copper accelerate TRH-like peptide synthesis in male rat pancreas and reproductive tissues SO PEPTIDES LA English DT Article DE prostate; epididymis; testis; RIA; HPLC ID THYROTROPIN-RELEASING-HORMONE; MALE WISTAR RATS; BETA-CELL LINES; ANTIEPILEPTIC DRUGS; IN-VITRO; HISTONE DEACETYLASE; EPILEPTIC PATIENTS; MOOD STABILIZER; SERUM-INSULIN; FOLLICULAR CELLS AB Treatment with valproate (Valp) facilitates the synthesis of TRH-like peptides (pGlu-X-Pro-NH2) in rat brain where "X" can be any amino acid residue. Because high levels of TRH-like peptides occur in the pancreas and pGlu-Glu-Pro-NH2 (Glu-TRH) has been shown to be a fertilization promoting peptide, we hypothesized that these peptides mediate some of the metabolic and reproductive side effects of Valp. Male WKY rats were treated with Valp acutely (AC), chronically (CHR) or chronically followed by a 2 day withdrawal (WD). AC, CHR and WD treatments significantly altered TRH and/or TRH-like peptide levels in pancreas and reproductive tissues. Glu-TRH was the predominant TRH-like peptide in epididymis, consistent with its fertilization promoting activity. Glu-TRH levels in the epididymis increased 3-fold with AC Valp. Phe-TRH, the most abundant TRH-like peptide in the pancreas, increased 4-fold with AC Valp. Phe-TRH inhibits both basal and TRH-stimulated insulin release. Large dense core vesicles (LDCV's) contain a copper-dependent enzyme responsible for the post-translational processing of precursors of TRH and TRH-like peptides. Copper (500 mu M) increased the in vitro C-terminal amidation of TRH-like peptides by 8- and 4-fold during 24 degrees C incubation of homogenates of pancreas and testis, respectively. Valp (7 mu M) accelerated 3-fold the processing of TRH and TRH-like peptide precursors in pancreatic LDCV's incubated at 24 degrees C. We conclude that copper, an essential cofactor for TRH and TRH-like peptide biosynthesis that is chelated by Valp, mediates some of the metabolic and reproductive effects of Valp treatment via acceleration of intravesicular synthesis and altered release of these peptides. (c) 2006 Published by Elsevier Inc. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Dept Biobehav Sci, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Res Serv, Bldg 114,Rm 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Eugene.Pekary@med.va.gov NR 67 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2006 VL 27 IS 11 BP 2901 EP 2911 DI 10.1016/j.peptides.2006.07.014 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 109OW UT WOS:000242318900045 PM 16945452 ER PT J AU Motsinger, AA Ritchie, MD Shafer, RW Robbins, GK Morse, GD Labbe, L Wilkinson, GR Clifford, DB D'Aquila, RT Johnson, VA Pollard, RB Merigan, TC Hirsch, MS Donahue, JP Kim, RB Haas, DW AF Motsinger, Alison A. Ritchie, Marylyn D. Shafer, Robert W. Robbins, Gregory K. Morse, Gene D. Labbe, Line Wilkinson, Grant R. Clifford, David B. D'Aquila, Richard T. Johnson, Victoria A. Pollard, Richard B. Merigan, Thomas C. Hirsch, Martin S. Donahue, John P. Kim, Richard B. Haas, David W. TI Multilocus genetic interactions and response to efavirenz-containing regimens: an Adult AIDS Clinical Trials Group study SO PHARMACOGENETICS AND GENOMICS LA English DT Article; Proceedings Paper CT 13th Conference on Retroviruses and Opportunistic Infections CY FEB 05-09, 2006 CL Denver, CO DE HIV therapy-efavirenz; multifactor dimensionality reduction; pharmacogenomics ID MULTIFACTOR-DIMENSIONALITY REDUCTION; SEQUENTIAL 3-DRUG REGIMENS; P-GLYCOPROTEIN EXPRESSION; HIV-INFECTED INDIVIDUALS; MDR1 GENE; CYTOCHROME P4502B6; DIGOXIN PHARMACOKINETICS; REGRESSION-ANALYSIS; ALLELIC VARIANTS; INITIAL THERAPY AB Objective For the HIV-1 reverse transcriptase inhibitor efavirenz, variant drug transporter gene ABCB1 may predict virologic response but not plasma efavirenz exposure. Conversely, variant drug metabolizing enzyme gene CYP2B6 predicts greater plasma efavirenz exposure but not virologic response. We examined whether long-term responses to efavirenz, and/or plasma efavirenz exposure, are better predicted by multilocus genetic interactions than by individual polymorphisms. Materials and methods We studied anti retroviral-naive study participants randomized to receive efavirenz (with or without nelfinavir) plus two nucleoside analogues in study ACTG 384, and who had DNA available for analysis. Participants were followed up for up to 3 years. Nine single nucleotide polymorphisms in ABCB1, CYP2B6, CYP3A4, CYP3A5 and CYP2C19 were identified. Gene-gene interactions were identified using multifactor dimensionality reduction. Results Among 340 efavirenz recipients, higher efavirenz AUC(24h) values were associated with a single locus model involving CYP2B6 516G > T (73% accuracy; P < 0.001). This was also the best model among blacks (69% accuracy; P < 0.001), whereas among whites the best model involved a gene-gene interaction between CYP2B6516G > T and ABCB1 2677G > T (82% accuracy, P < 0.001). Among 155 participants who received efavirenz without nelfinavir, virologic failure was associated with a two-locus interaction between ABCB1 2677G > T and CYP2B6 516G > T (65% accuracy, P < 0.001). Toxicity failure was best predicted by an interaction between ABCB1 2677G > T and ABCB1 3435C > T (71% accuracy, P < 0.001). Conclusions Multilocus genetic interactions between variant drug metabolism and transporter genes may predict efavirenz pharmacokinetics and treatment responses. This finding may have implications for better individualizing antiretroviral therapy. C1 Vanderbilt Univ, Ctr Human Genet Res, Div Infect Dis, Sch Med, Nashville, TN 37203 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif Davis, Davis, CA 95616 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Washington Univ, St Louis, MO USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Med Sch Birmingham, Birmingham, AL USA. Univ Montreal, Montreal, PQ, Canada. RP Haas, DW (reprint author), Vanderbilt Univ, Ctr Human Genet Res, Div Infect Dis, Sch Med, 345 24th Ave N,Suite 105, Nashville, TN 37203 USA. EM david.w.haas@vanderbilt.edu RI Robbins, Gregory/F-7988-2011; Ritchie, Marylyn/C-1114-2012 FU NCRR NIH HHS [RR000095]; NHLBI NIH HHS [HL65962]; NIAID NIH HHS [AI27658, AI25903, AI27659, AI27666, AI29193, AI38855, AI38858, AI46339, AI54999]; NIGMS NIH HHS [GM31304]; NINDS NIH HHS [NS32228] NR 52 TC 39 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD NOV PY 2006 VL 16 IS 11 BP 837 EP 845 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 104PU UT WOS:000241971500009 PM 17047492 ER PT J AU Levine, GN Berger, PB Cohen, DJ Maree, AO Rosenfield, K Wiggins, BS Spinler, SA AF Levine, Glenn N. Berger, Peter B. Cohen, David J. Maree, Andrew O. Rosenfield, Kenneth Wiggins, Barbara S. Spinler, Sarah A. TI Newer pharmacotherapy in patients undergoing percutaneous coronary interventions: A guide for pharmacists and other health care professionals - Expert opinion from the American Heart Association's Diagnostic and Interventional Catheterization Committee and Council on Clinical Cardiology, and the American College of Clinical Pharmacy's Cardiology Practice Research Network SO PHARMACOTHERAPY LA English DT Article DE percutaneous coronary intervention; PCI; antiplatelet drugs; antithrombin drugs; clopidogrel; enoxaparin; bivalirudin; eptifibatide; abciximab; tirofiban; pharmacotherapy utilization guidelines ID GLYCOPROTEIN-IIB/IIIA BLOCKADE; LOW-MOLECULAR-WEIGHT; HIGH-RISK PATIENTS; ACUTE MYOCARDIAL-INFARCTION; REPLACE-2 RANDOMIZED-TRIAL; ADVERSE CARDIAC EVENTS; ANTIPLATELET THERAPY; STENT IMPLANTATION; CLOPIDOGREL PRETREATMENT; UNSTABLE ANGINA AB Significant advances in pharmacotherapy for patients undergoing percutaneous coronary intervention (PCI) have occurred during the past decade, including the introduction and approval of new antithrombin and antiplatelet therapies, as well as modifications in dosing, administration, and/or duration of older pharmacotherapy regimens. Also, off-label (i.e., not approved by the United States Food and Drug Administration) use of certain agents has become common. Given the novel nature of these agents and the nuances of therapy, the pharmacist and other health care professionals should play an integral role in collaboration with interventional cardiologists in development of hospital protocols, determination of appropriate agent selection, assessment of patient renal function and hematologic status, dosing, and monitoring for adverse effects. In this guide, the newer antiplatelet and antithrombin drugs that may be used during PCI are reviewed, and recommendations regarding the proper administration of these agents are provided. Key Words: percutaneous coronary intervention, PCI, antiplatelet drugs, antithrombin drugs, clopidogrel, enoxaparin, bivalirudin, eptifibatide, abciximab, tirofiban, pharmacotherapy utilization guidelines. C1 Baylor Coll Med, Houston, TX 77030 USA. Geisinger Med Clin, Danville, PA USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Virginia, Sch Med, Charlottesville, VA 22903 USA. Univ Philippines, Coll Pharm, Philadelphia, PA USA. RP Spinler, SA (reprint author), Univ Sci Philadelphia, 600 S 43rd St, Philadelphia, PA 19104 USA. NR 99 TC 12 Z9 13 U1 0 U2 3 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 2006 VL 26 IS 11 BP 1537 EP 1556 DI 10.1592/phco.26.11.1537 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 101ZG UT WOS:000241779600001 PM 17064198 ER PT J AU Troemel, ER Chu, SW Reinke, V Lee, SS Ausubel, FM Kim, DH AF Troemel, Emily R. Chu, Stephanie W. Reinke, Valerie Lee, Siu Sylvia Ausubel, Frederick M. Kim, Dennis H. TI p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans SO PLOS GENETICS LA English DT Article ID EXTENDS LIFE-SPAN; CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; TRANSCRIPTION FACTOR; PATHOGEN RECOGNITION; SIGNALING PATHWAY; OXIDATIVE STRESS; DAF-16; SYSTEM; PROTEIN AB The PMK-1 p38 mitogen-activated protein kinase pathway and the DAF-2-DAF-16 insulin signaling pathway control Caenorhabditis elegans intestinal innate immunity. pmk-1 loss-of-function mutants have enhanced sensitivity to pathogens, while daf-2 loss-of-function mutants have enhanced resistance to pathogens that requires upregulation of the DAF-16 transcription factor. We used genetic analysis to show that the pathogen resistance of daf-2 mutants also requires PMK-1. However, genome-wide microarray analysis indicated that there was essentially no overlap between genes positively regulated by PMK-1 and DAF-16, suggesting that they form parallel pathways to promote immunity. We found that PMK-1 controls expression of candidate secreted antimicrobials, including C-type lectins, ShK toxins, and CUB-like genes. Microarray analysis demonstrated that 25% of PMK-1 positively regulated genes are induced by Pseudomonas aeruginosa infection. Using quantitative PCR, we showed that PMK-1 regulates both basal and infection-induced expression of pathogen response genes, while DAF-16 does not. Finally, we used genetic analysis to show that PMK-1 contributes to the enhanced longevity of daf-2 mutants. We propose that the PMK-1 pathway is a specific, indispensable immunity pathway that mediates expression of secreted immune response genes, while the DAF-2-DAF-16 pathway appears to regulate immunity as part of a more general stress response. The contribution of the PMK-1 pathway to the enhanced lifespan of daf-2 mutants suggests that innate immunity is an important determinant of longevity. C1 MIT, Dept Biol, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. RP Kim, DH (reprint author), MIT, Dept Biol, Cambridge, MA USA. EM dhkim@mit.edu FU NIA NIH HHS [R56 AG024425, AG024425-01, R01 AG024425]; NIAID NIH HHS [AI053595, AI064332, K08 AI053595, R01 AI064332]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 58 TC 256 Z9 293 U1 3 U2 35 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2006 VL 2 IS 11 BP 1725 EP 1739 AR e183 DI 10.1371/journal.pgen.0020183 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 110JM UT WOS:000242374600006 PM 17096597 ER PT J AU Morris, EJ Michaud, WA Ji, JY Moon, NS Rocco, JW Dyson, NJ AF Morris, Erick J. Michaud, William A. Ji, Jun-Yuan Moon, Nam-Sung Rocco, James W. Dyson, Nicholas J. TI Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo SO PLOS GENETICS LA English DT Article ID S-PHASE ENTRY; CELL-CYCLE; GENE-EXPRESSION; DROSOPHILA-MELANOGASTER; E2F1-INDUCED APOPTOSIS; TARGET GENES; E2F; DEATH; RB; RETINOBLASTOMA AB Retinoblastoma protein and E2-promoter binding factor (E2F) family members are important regulators of G1-S phase progression. Deregulated E2F also sensitizes cells to apoptosis, but this aspect of E2F function is poorly understood. Studies of E2F-induced apoptosis have mostly been carried out in tissue culture cells, and the analysis of the factors that are important for this process has been restricted to the testing of a few candidate genes. Using Drosophila as a model system, we have generated tools that allow genetic modifiers of E2F-dependent apoptosis to be identified in vivo and developed assays that allow effects on E2F-induced apoptosis to be studied in cultured cells. Genetic interactions show that dE2F1-dependent apoptosis in vivo involves dArk/Apaf1 apoptosome-dependent activation of both initiator and effector caspases and is sensitive to levels of Drosophila inhibitor of apoptosis-1 (dIAP1). Using these approaches, we report the surprising finding that apoptosis inhibitor-5/antiapoptosis clone-11 (Api5/Aac11) is a critical determinant of dE2F1-induced apoptosis in vivo and in vitro. This functional interaction occurs in multiple tissues, is specific to E2F-induced apoptosis, and is conserved from flies to humans. Interestingly, Api5/Aac11 acts downstream of E2F and suppresses E2F-dependent apoptosis without generally blocking E2F-dependent transcription. Api5/Aac11 expression is often upregulated in tumor cells, particularly in metastatic cells. We find that depletion of Api5 is tumor cell lethal. The strong genetic interaction between E2F and Api5/Aac11 suggests that elevated levels of Api5 may be selected during tumorigenesis to allow cells with deregulated E2F activity to survive under suboptimal conditions. Therefore, inhibition of Api5 function might offer a possible mechanism for antitumor exploitation. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA USA. EM dyson@helix.mgh.harvard.edu FU NCI NIH HHS [F32 CA088474, P01 CA095281, P01CA095281, F32CA88474]; NIGMS NIH HHS [R01 GM053203, GM53203] NR 62 TC 62 Z9 64 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2006 VL 2 IS 11 BP 1834 EP 1848 AR e196 DI 10.1371/journal.pgen.0020196 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 110JM UT WOS:000242374600014 PM 17112319 ER PT J AU Wang, JH Cai, Y Penland, R Chauhan, S Miesfeld, RL Ittmann, M AF Wang, Jianghua Cai, Yi Penland, Rebecca Chauhan, Sanjay Miesfeld, Roger L. Ittmann, Michael TI Increased expression of the metastasis-associated gene Ehm2 in prostate cancer SO PROSTATE LA English DT Article DE Ehm2; prostate cancer; recurrence; cell adhesion; metastasis ID GROWTH-FACTOR RECEPTOR-4; FERM DOMAIN; INTEGRIN ACTIVATION; MURINE MELANOMA; ARG(388) ALLELE; CELL-ADHESION; PROGRESSION; PROGNOSIS; MEMBRANE; PROTEINS AB BACKGROUND. Alterations of fibroblast growth factors and their receptors contribute to prostate cancer progression by enhancing cell survival, motility, and proliferation. The expression of the FGFR-4 Arg 388 variant is correlated with the occurrence of pelvic lymph node metastasis and biochemical (PSA) recurrence in men undergoing radical prostatectomy. Ehm2 is an androgen-regulated gene that has been associated with metastasis in other systems, so we sought to determine if it is expressed in prostate cancer and if the FGFR-4 Arg 388 variant can increase its expression. METHODS. Expression of Ehm2 was examined by quantitative RT-PCR and Western blotting in prostate cell lines and by quantitative RT-PCR, in situ hybridization, and immunohistochemistry in prostate tissues. The effect of Ehm2 expression on collagen IV adhesion was tested by transient overexpression and RNA interference. RESULTS. Ehm2 expression is upregulated in prostate cancer cell lines and prostate cancer tissues. Expression of the FGFR-4 Arg(388) variant results in increased expression of Ehm2. Increased expression of Ehm2 leads to decreased adhesion to collagen IV, which has been associated with metastasis in cancers. Analysis of tissue microarrays revealed that increased Ehm2 expression is associated with biochemical recurrence after radical prostatectomy, which is indicative of more aggressive disease. CONCLUSIONS. Ehm2 is overexpressed in prostate cancer and may enhance disease progression and metastasis. C1 Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Univ Arizona, Dept Biochem & Mol Biophys, Tucson, AZ USA. RP Ittmann, M (reprint author), Michael E DeBakey VAMC, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU NCI NIH HHS [P50CA058204] NR 37 TC 19 Z9 19 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD NOV 1 PY 2006 VL 66 IS 15 BP 1641 EP 1652 DI 10.1002/pros.20474 PG 12 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 099QE UT WOS:000241609600007 PM 16927306 ER PT J AU Dowben, JS AF Dowben, Jonathan S. TI Current occupational aspects of army psychiatry SO PSYCHIATRIC ANNALS LA English DT Article C1 Birmingham VAMC, Outpatient Menta Hlth Clin, Birmingham, AL 35233 USA. RP Dowben, JS (reprint author), Birmingham VAMC, Outpatient Menta Hlth Clin, 700 19th St S, Birmingham, AL 35233 USA. EM jonathan.dowben@va.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2006 VL 36 IS 11 BP 764 EP + PG 16 WC Psychiatry SC Psychiatry GA 107SK UT WOS:000242191100007 ER PT J AU Schouten, R AF Schouten, Ronald TI Workplace violence: An overview for practicing clinicians SO PSYCHIATRIC ANNALS LA English DT Article ID INTERPERSONAL VIOLENCE; TARGETED VIOLENCE; THREAT ASSESSMENT; POTENTIAL CAUSES; EVALUATING RISK; AGGRESSION; BEHAVIOR; PREDICTORS; DISORDERS; FREQUENCY C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. RP Schouten, R (reprint author), 15 Parkman St WAC 812, Boston, MA 02114 USA. EM rschouten@partners.org NR 36 TC 1 Z9 1 U1 3 U2 7 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2006 VL 36 IS 11 BP 790 EP 797 PG 8 WC Psychiatry SC Psychiatry GA 107SK UT WOS:000242191100010 ER PT J AU Reade, JM AF Reade, Julia M. TI Impaired physicians: Role of the occupational psychiatrist SO PSYCHIATRIC ANNALS LA English DT Article ID DISCIPLINARY ACTION; MEDICAL-SCHOOL; BEHAVIOR C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reade, JM (reprint author), 321 Walnut St 423, Newtonville, MA 02460 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2006 VL 36 IS 11 BP 798 EP 803 PG 6 WC Psychiatry SC Psychiatry GA 107SK UT WOS:000242191100011 ER PT J AU Golier, JA Schmeidler, J Legge, J Yehuda, R AF Golier, Julia A. Schmeidler, James Legge, Juliana Yehuda, Rachel TI Enhanced cortisol suppression to dexamethasone associated with Gulf War deployment SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Gulf War illness; medically unexplained illnesses; cortisol; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; REPORTED PHYSICAL HEALTH; CHRONIC-FATIGUE-SYNDROME; PITUITARY-ADRENAL AXIS; COMBAT VETERANS; PYRIDOSTIGMINE BROMIDE; CIRCADIAN VARIATION; PLASMA-CORTISOL; SYMPTOMS; RESPONSES AB Objective: To examine whether PTSD or post-deployment health symptoms in veterans of the first Gulf War (Operation Desert Shield/Storm) are associated with enhanced suppression of the pituitary-adrenal axis to low-dose dexamethasone (DEX). Method: Plasma cortisol and lymphocyte glucocorticoid receptor (GR) number were measured at 08:00h on two consecutive days, before and after administration of 0.5 mg of DEX at 23:00h in 42 male Gulf War veterans (14 without psychiatric illness, 16 with PTSD only, and 12 with both PTSD and MDD) and 12 healthy mate veterans not deployed to the Gulf War or another war zone. Results: In the absence of group differences in basal cortisol levels or GR number, Gulf War veterans without psychiatric illness and Gulf War veterans with PTSD only had significantly greater cortisol suppression to DEX than non-deployed veterans and Gulf War veterans with both PTSD and MDD. Gulf War deployment was associated with significantly greater cortisol suppression to DEX controlling for weight, smoking status, PTSD, and MDD; PTSD was not associated with response to DEX. Among Gulf War veterans musculoskeletal symptoms were significantly associated with cortisol suppression and those who reported taking anti-nerve gas pills (i.e., pyridostigmine bromide) during the war had significantly greater DEX-induced cortisol suppression than those who did not. Conclusions: The data demonstrate that alterations in neuroendocrine function are associated with deployment to the Gulf War and post-deployment musculosketetal symptoms, but not PTSD. Additional studies are needed to examine the relationship of enhanced glucocorticoid responsivity to deployment exposures and chronic unexplained medical symptoms in Gulf War veterans. (c) 2006 Elsevier Ltd. All. rights reserved. C1 James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Golier, JA (reprint author), James J Peters VA Med Ctr, Dept Psychiat, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM julia.golier@med.va.gov FU NCRR NIH HHS [5M01 RR 00071] NR 52 TC 24 Z9 24 U1 4 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 2006 VL 31 IS 10 BP 1181 EP 1189 DI 10.1016/j.psyneuen.2006.08.005 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 120OZ UT WOS:000243095800005 PM 17049422 ER PT J AU Pajer, K Tabbah, R Gardner, W Rubin, RT Czambel, RK Wang, Y AF Pajer, Kathleen Tabbah, Rhonda Gardner, William Rubin, Robert T. Czambel, R. Kenneth Wang, Yun TI Adrenal androgen and gonadal hormone levels in adolescent girls with conduct disorder SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE female antisocial behavior; female conduct disorder; adrenal androgens; gonadal hormones; DHEA-s; testosterone; free testosterone index ID OPPOSITIONAL-DEFIANT DISORDER; AGGRESSIVE-BEHAVIOR; DEHYDROEPIANDROSTERONE-SULFATE; SALIVARY TESTOSTERONE; BINDING GLOBULIN; DEPENDENT AGGRESSION; PLASMA TESTOSTERONE; SOCIAL-DOMINANCE; COMMUNITY SAMPLE; FOLLOW-UP AB There are few data on the biological correlates of female antisocial behavior. This study compared adrenal androgen and gonadal hormone levels in adolescent girls with conduct disorder (CID) to girls without any psychiatric disorder (NC). We studied 87 girls, (47 CID; 36 NC), ages 15-17 years, obtaining three blood samples, drawn 20 min apart between 8 and 9 AM in the first 72 h of the onset of menstrual flow. Plasma was assayed for testosterone, estradiol, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), sex hormone binding globulin (SHBG), and cortisol; area under the curve (AUC) for each of the three samples was used in the data analysis. We also calculated the Free Testosterone Index, Free Estrogen Index, Index of Hyperandrogenism and cortisol to DHEA ratio. In addition to receiving a full psychiatric interview, each girt completed a self-report questionnaire on general aggression. Main hormone analyses controlled for potentially confounding variables such as psychiatric comorbidity and race. Girls with CID had significantly lower cortisol to DHEA ratios, but did not differ from NC girls on any other hormone variable. Girls with symptoms of aggressive CD had significantly higher mean free testosterone indexes, lower SHBG Levels, and Lower cortisol. to DHEA ratios than girls with non-aggressive CD. Girls with CD scored higher on the aggression questionnaire, but there was no association between general aggression and any hormone variable for the sample. Our data suggest that girls with CD, particularly aggressive CID, have lower cortisol to DHEA ratios, higher levels of free testosterone, and lower levels of SHBG. Clinical and research implications of these findings are discussed. (c) 2006 Elsevier Ltd. ALL rights reserved. C1 Ohio State Univ, Dept Pediat, Columbus Childrens Res Inst, Coll Med & Publ Hlth, Columbus, OH 43210 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA USA. Allegheny Gen Hosp, Allegheny Singer Res Inst, Pittsburgh, PA 15212 USA. RP Pajer, K (reprint author), Ohio State Univ, Dept Pediat, Columbus Childrens Res Inst, Coll Med & Publ Hlth, Columbus, OH 43210 USA. EM pajerk@pediatrics.ohio-state.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIMH NIH HHS [MH 01285-04] NR 86 TC 53 Z9 57 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 2006 VL 31 IS 10 BP 1245 EP 1256 DI 10.1016/j.psyneuen.2006.09.005 PG 12 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 120OZ UT WOS:000243095800011 PM 17126492 ER PT J AU Loftis, JM Wall, JM Pagel, RL Hauser, P AF Loftis, Jennifer M. Wall, Jennifer M. Pagel, Rebecca L. Hauser, Peter TI Administration of pegylated interferon-alpha-2a or -2b does not induce sickness behavior in Lewis rats SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE pegylated interferon; depression; sickness behavior; forced swim test; serotonin ID FORCED SWIMMING TEST; ALPHA-INTERFERON; HEPATITIS-C; GAMMA; ASSOCIATION; IMMOBILITY; DEPRESSION; INJECTION; SYMPTOMS; THERAPY AB Repeated administration of interferon-a (IFN-alpha) or pegylated IFN-alpha to patients with chronic hepatitis C viral infection induces a flu-like syndrome as well as neuropsychiatric side effects, which are well recognized, but poorly understood. Although pegylation appears to have improved viral response rates in patients with hepatitis C, there are still neurotoxicities associated with pegylated IFN-alpha therapy, in particular, depression, which can compromise and sometime prevent successful completion of antiviral treatment. This study assessed the effects of two forms of pegylated IFN-alpha [peginterferon-alfa-2a (PEG-2a) and peginterferon-alfa-2b (PEG-2b)] in rats in order to develop an animal model of IFN-induced "depression" (often described as sickness behavior) that can be used to more comprehensively investigate the neurochemical mechanisms of IFN-induced depression. Sixty mate and female Lewis rats were randomly assigned to one of six treatment groups: (1) saline (SAL)+SAL (2) SAL+PEG-2a; (3) SAL+PEG-2b; (4) selective serotonin reuptake inhibitor (SSRI)+SAL, (5) SSRI+PEG-2a; (6) SSRI+PEG-2b. Rats were pretreated with intraperitoneal (i.p.) saline (0.9%) or 7.5 mg/kg/day fluoxetine for 1 week, followed by 3 weeks of concurrent i.p. administration of 650 mu g/wk of PEG-2a or PEG-2b.Using locomotor activity, the forced swim test, and weight gain as behavioral measures of sickness behavior, our data showed that Lewis rats did not develop an IFN-induced "depressive syndrome." Western blot analyses of brain and liver tissue indicated that signal transducer and activator of transcripton (STAT1) was not phosphorylated following IFN-alpha administration, suggesting that the pegylated compounds may not have bound type I IFN receptors in the rat. Collectively, our data suggest that Lewis rats are likely not a useful model to study IFN-induced depression. (c) 2006 Elsevier Ltd. All rights reserved. C1 Oregon Hlth & Sci Univ, Dept Psychiat, Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Internal Med, Portland VA Med Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, JENS Lab, Portland, OR 97239 USA. Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR 97239 USA. RP Loftis, JM (reprint author), Oregon Hlth & Sci Univ, Dept Psychiat, Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Mail Code P3MHAdm,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM loftisj@ohsu.edu NR 25 TC 20 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 2006 VL 31 IS 10 BP 1289 EP 1294 DI 10.1016/j.psyneuen.2006.07.006 PG 6 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 120OZ UT WOS:000243095800015 PM 17049181 ER PT J AU Inslicht, SS Marmar, CR Neylan, TC Metzler, TJ Hart, SL Otte, C McCaslin, SE Larkin, GL Hyman, KB Baum, A AF Inslicht, Sabra S. Marmar, Charles R. Neylan, Thomas C. Metzler, Thomas J. Hart, Stacey L. Otte, Christian McCaslin, Shannon E. Larkin, G. Luke Hyman, Kelly B. Baum, Andrew TI Increased cortisol in women with intimate partner violence-related posttraumatic stress disorder (vol 37, pg 825, 2006) SO PSYCHONEUROENDOCRINOLOGY LA English DT Correction C1 Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Univ Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA. Dept Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Hamburg, Hosp Eppendorf, Dept Psychiat & Psychotherapy, D-20246 Hamburg, Germany. Univ Texas, Div Emergency Med, Dept Surg, SW Med Ctr,Parkland Mem Hosp, Dallas, TX 75390 USA. Ctr Hlth Equ Res & Promot, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15240 USA. RP Inslicht, SS (reprint author), Univ Pittsburgh, Dept Psychol, Sennott Sq,3rd Floor,210 S Bouquet St, Pittsburgh, PA 15260 USA. EM sabra@itsa.ucsf.edu RI Hart, Stacey/E-4819-2011 NR 1 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 2006 VL 31 IS 10 BP 1295 EP 1296 DI 10.1016/j.psyneuen.2006.08.002 PG 2 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 120OZ UT WOS:000243095800016 ER PT J AU Kreher, DA Holcomb, PJ Kuperberg, GR AF Kreher, Donna A. Holcomb, Phillip J. Kuperberg, Gina R. TI An electrophysiological investigation of indirect semantic priming SO PSYCHOPHYSIOLOGY LA English DT Article DE ERP; N400; semantic; memory; priming ID EVENT-RELATED POTENTIALS; AUTOMATIC SPREADING ACTIVATION; LEXICAL DECISION; MEMORY; RETRIEVAL; N400; VOLUNTEERS; REPETITION; CAPACITY; WORDS AB In two experiments, direct and indirect semantic priming were measured using event-related potentials. In Experiment 1, participants rated the relatedness between prime and target on a seven-point scale. In Experiment 2, participants simply read the primes and targets as they monitored for a semantic category in probe filler items. Significant direct and indirect N400 priming effects were observed in both experiments. In Experiment 1, the indirect N400 priming effect remained significant when indirectly related and unrelated word pairs were matched for participants' explicit relatedness judgments. In both experiments, the indirect N400 priming effects were preserved when indirectly related and unrelated word pairs were matched on more global and objective measures of semantic similarity. These findings are discussed in the context of current theoretical models of semantic memory and semantic priming. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Kreher, DA (reprint author), 490 Boston Ave, Medford, MA 02155 USA. EM dkreher@neurocog.psy.tufts.edu FU NICHD NIH HHS [R01 HD025889-16, R01 HD025889, R01 HD25889, R01 HD043251, R01 HD043251-04]; NIMH NIH HHS [K23 MH02034, K23 MH002034, R01 MH071635] NR 35 TC 25 Z9 26 U1 5 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2006 VL 43 IS 6 BP 550 EP 563 DI 10.1111/j.1469-8986.2006.00460.x PG 14 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 099VV UT WOS:000241626200004 PM 17076811 ER PT J AU Smoller, JW Pollack, MH Wassertheil-Smoller, S Brunner, R Curb, D Torner, J Oberman, A Hendrix, SL Hsia, J Sheps, DS AF Smoller, Jordan W. Pollack, Mark H. Wassertheil-Smoller, Sylvia Brunner, Robert Curb, David Torner, James Oberman, Albert Hendrix, Susan L. Hsia, Judith Sheps, David S. TI Panic attacks, daily life ischemia, and chest pain in postmenopausal women SO PSYCHOSOMATIC MEDICINE LA English DT Article DE daily life ischemia; postmenopausal women; panic; chest pain; panic disorder ID CORONARY-HEART-DISEASE; RATE-VARIABILITY; ARTERY-DISEASE; PHOBIC ANXIETY; UNITED-STATES; DISORDER; RISK; SYMPTOMS; PREVALENCE; MORTALITY AB Background: Chest pain is a common symptom of panic attacks, but little is known about the relationship in older women among panic attacks, chest pain, and daily life ischemia. Methods: The authors conducted a cross-sectional survey of 3063 community-dwelling, generally healthy postmenopausal women enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study in 10 clinical centers of the 40-center Women's Health Initiative. Participants, ages 50 to 79 years, completed a questionnaire about occurrence of panic attacks in the previous 6 months and underwent 24-hour ambulatory electrocardiogram monitoring (AECG); 2705 women had valid AECG recordings and panic attack questionnaires. ST depression on AECG, heart rate variability (HRV), and chest pain episodes were compared among women with and without a 6-month history of panic attack. Results: There was no difference in overall prevalence of ischemic episodes during AECG between women with and without panic attacks. Women with a recent history of panic were more likely to experience chest pain during AECG after controlling for potential confounders (odds ratio [OR] = 2.01; 95% confidence interval [CI] 1.40-2.88), including both nonischemic (OR = 1.83; 95% Cl = 1.26-2.65) and ischemic chest pain (OR = 4.94; 95% Cl 1.41-17.30). Although mean HRV was lower in those with panic attacks (p =.0 17), this was not significant after controlling for confounders. Conclusions: Postmenopausal women with a recent history of panic attacks do not appear to have more daily life ischemia as measured by occurrence of ST depression during 24-hour monitoring, but do have more chest pain and possibly lower HRV, suggesting that even sporadic panic attacks may be related to cardiovascular risk. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Iowa, Iowa City, IA USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Univ Florida, Gainesville, FL USA. Malcom Randall VA Med Ctr, Gainesville, FL USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 32 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2006 VL 68 IS 6 BP 824 EP 832 DI 10.1097/01.psy.0000244383.19453.c5 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 108SK UT WOS:000242259300003 PM 17101813 ER PT J AU Kerwin, WS O'Brien, KD Ferguson, MS Polissar, N Hatsukami, TS Yuan, C AF Kerwin, William S. O'Brien, Kevin D. Ferguson, Marina S. Polissar, Nayak Hatsukami, Thomas S. Yuan, Chun TI Inflammation in carotid atherosclerotic plaque: A dynamic contrast-enhanced MR imaging study SO RADIOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; HISTOLOGICAL CLASSIFICATION; DENSITY-LIPOPROTEIN; HIGH-RESOLUTION; LESIONS; PROGRESSION; ASSOCIATION; EXPRESSION; ATHEROMA; SERUM AB Purpose: To prospectively evaluate if there is an association between plaque enhancement at magnetic resonance (MR) imaging and proinflammatory cardiovascular risk factors and plaque content. Materials and Methods: This study was performed with informed consent, HIPAA compliance, and institutional review board approval. Contrast agent dynamics within carotid plaques were measured in 30 patients (29 men, one woman; mean age, 67.7 years +/- 10.7 [standard deviation]) who were scheduled to undergo carotid endarterectomy. Measurements were based on kinetic modeling of images obtained at 15-second intervals during which a gadolinium-based contrast agent was injected. The time-varying signal intensities within the plaques were used to estimate the fractional plasma volume (v(p)) and transfer constant (K-trans) of contrast material into the extracellular space. Pearson correlation coefficients were computed between blinded MR measurements and histologic measurements of plaque composition, including macrophages, neovasculature, necrotic core, calcification, loose matrix, and dense fibrous tissue. Correlation coefficients or mean differences were computed regarding clinical markers of cardiovascular risk. Results: Analyzable MR images and histologic results were obtained in 27 patients. Measurements of Ktrans correlated with macrophage (r = 0.75, P < .001), neovasculature (r = 0.71, P < .001), and loose matrix (r = 0.50, P = .01) content. Measurements of vp correlated with macrophage (r = 0.54, P = .004), neovasculature (r = 0.68, P < .001), and loose matrix (r = 0.42, P = .03) content. For clinical parameters, significant associations were correlated with Ktrans only, with decreased high-density lipoprotein levels (r = -0.66, P < .001) and elevated K-trans measurements in smokers compared with nonsmokers (mean, 0.134 min(-1) vs 0.074 min(-1), respectively; P = .01). Conclusion: The correlations between Ktrans and histologic markers of inflammation suggest that Ktrans is a quantitative and non=invasive marker of plaque inflammation, which is further supported by the correlation of Ktrans with proinflammatory cardiovascular risk factors, decreased high-density lipoprotein levels, and smoking. C1 Univ Washington, Dept Radiol, Seattle, WA 98109 USA. Univ Washington, Div Cardiol, Seattle, WA 98109 USA. Univ Washington, Dept Surg, Seattle, WA 98109 USA. Mt Whisper Light Stat Consulting, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kerwin, WS (reprint author), Univ Washington, Dept Radiol, 815 Mercer St, Seattle, WA 98109 USA. EM bkerwin@u.washington.edu FU NHLBI NIH HHS [P01 HL072262, R01 HL073401, R01-HL56874]; NIBIB NIH HHS [EB-01975]; PHS HHS [P01-072262] NR 37 TC 139 Z9 158 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2006 VL 241 IS 2 BP 459 EP 468 DI 10.1148/radiol.2412051336 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 098KM UT WOS:000241519400017 PM 16966482 ER PT J AU Court, LE D'Amico, AV Kadam, D Cormack, R AF Court, Laurence E. D'Amico, Anthony V. Kadam, Dnyanesh Cormack, Robert TI Motion and shape change when using an endorectal balloon during prostate radiation therapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE prostate; endorectal balloon; immobilization; inter-fraction motion ID CONFORMAL RADIOTHERAPY; RANDOMIZED-TRIAL; DOSE-RESPONSE; CANCER; MARKERS; INTERFRACTION; LOCALIZATION; IRRADIATION; SYSTEM; ERROR AB Purpose: To investigate motion and shape change when using an endorectal balloon (ERB) in patients receiving radiotherapy for prostate cancer. Methods: In nine patients treated for prostate cancer using an ERB, the anterior wall of the ERB was contoured on right lateral images taken immediately before irradiation, and on left lateral images taken immediately after irradiation. Changes in the contours were used to calculate inter-fraction shape change and inter-imaging motion and shape change. Inter-imaging motion describes changes that occur after the right lateral image is taken that are seen in the left lateral image. Results: Eighty-six percent of all inter-imaging shifts of the anterior wall of the ERB were in the posterior direction (mean: 1.8 mm, 1 SD: 1.8 mm, maximum posterior shift: 2.8-7.2 mm). The inter-fraction shape change (1 SD) of the anterior wall was equivalent to a change in the angle of the balloon of 2.5-5.7 degrees, with a range of 8-20 degrees, depending on the patient. Inter-imaging shape changes were similar in size. Conclusions: The inter-imaging motion and shape changes may be explained by the patient relaxing some time after insertion of the ERB, indicating that it could be reduced by a waiting period after insertion before irradiation. Development of image-guided localization strategies should consider intra-fraction motion and also inter-and intra-fraction shape change. (c) 2006 Published by Elsevier Ireland Ltd. C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Court, LE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM lcourt@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 21 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD NOV PY 2006 VL 81 IS 2 BP 184 EP 189 DI 10.1016/j.radonc.2006.10.004 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 114VX UT WOS:000242694800012 PM 17069915 ER PT J AU Kacmarek, RM AF Kacmarek, Robert M. TI NPPV in acute respiratory failure: Is it time to reconsider where it may be applied? SO RESPIRATORY CARE LA English DT Editorial Material ID POSITIVE-PRESSURE VENTILATION; RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE PULMONARY-DISEASE; NONINVASIVE VENTILATION; NASAL VENTILATION; FACE MASK; MULTICENTER; RISK; EXACERBATIONS; EXTUBATION C1 Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 20 TC 1 Z9 1 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD NOV PY 2006 VL 51 IS 11 BP 1226 EP 1227 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 103RE UT WOS:000241903600002 PM 17067402 ER PT J AU Adams, SG Anzueto, A Pugh, JA Lee, S Hazuda, HP AF Adams, Sandra G. Anzueto, Antonio Pugh, Jacqueline A. Lee, Shuko Hazuda, Helen P. TI Mexican American elders have similar severities of COPD despite less tobacco exposure than European American elders SO RESPIRATORY MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; tobacco; exposure; Mexican Americans; European Americans; ethnicity; severity ID SAN-ANTONIO; ETHNIC-DIFFERENCES; PULMONARY-DISEASE; RISK-FACTORS; MORTALITY; WOMEN; DIFFERENCE; HISPANICS; HEALTH; ASTHMA AB Introduction: Hispanics are the fastest growing ethnicity of the US population and the largest subset includes those of Mexican origin. Hispanics, including Mexican Americans (MAs), consistently report less tobacco exposure than European Americans (EAs), but limited data are available regarding differences in the clinical characteristics, severity of airflow obstruction, and functional status between MAs and EAs with chronic obstructive pulmonary disease (COPD). Methods: Participants in a community-based study of aging and frailty among MAs and EAs, San Antonio Longitudinal Study of Aging, underwent spirometry. Participants with spirometry values consistent with COPD by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria are described here. Results: Thirty-four percent (248/721) of the participants who underwent spirometry had evidence of GOLD Stages 1-4 COPD. Significantly more MAs with COPD reported being never smokers compared to EAs with COPD. Among those with COPD who also smoked, MAs reported significantly less tobacco exposure than EAs (115.7 vs. 32.4 pack-years, respectively), but both groups had surprisingly similar seventies of airflow obstruction. Additionally, MAs had worse functional status and perceived health than did EAs. Conclusions: Despite significantly less exposure to tobacco smoke, MAs with COPD had a similar degree of obstruction to airflow compared with EAs with COPD. Healthcare providers should have a high index of suspicion for COPD in MAs who are exposed to even small amounts of cigarette smoke. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Div Pulm Dis Crit Care Med, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, VERDICT, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Epidemiol, San Antonio, TX 78285 USA. RP Adams, SG (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect 111E, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM adamssg@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X FU NCRR NIH HHS [M01-RR-01346]; NIA NIH HHS [R01-AG16518, R01-AG10444] NR 28 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD NOV PY 2006 VL 100 IS 11 BP 1966 EP 1972 DI 10.1016/j.rmed.2006.02.023 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 100ZY UT WOS:000241709900013 PM 16626949 ER PT J AU Ouellette, H Salamipour, H Thomas, BJ Kassarjian, A Torriani, M AF Ouellette, Hugue Salamipour, Hamid Thomas, Bijoy J. Kassarjian, Ara Torriani, Martin TI Incidence and MR imaging features of fractures of the anterior process of calcaneus in a consecutive patient population with ankle and foot symptoms SO SKELETAL RADIOLOGY LA English DT Article DE anterior process; calcaneus; fracture; MR imaging ID SECUNDARIUS AB Objective: To determine the incidence, appearances and associated injuries of fractures affecting the anterior process of calcaneus from a general population with foot and ankle symptoms. Design and patients: A retrospective review of foot and ankle MR imaging procedures was performed for detection of cases with a fracture affecting the anterior process of calcaneus over a four year period. Radiographs, MR imaging studies, radiology reports, medical records, and operative notes were reviewed. Imaging analysis included fracture pattern, displacement, associated fractures, and presence of tendon and ligamentous injuries. Results: The incidence of anterior process of calcaneus fracture on MR imaging was 0.5% (14/2577). Fractures were more common in female subjects (71%, 10/14). Fracture orientation was predominantly vertical (93%, 13/14). No comminuted fractures were seen and only three fractures were displaced. Three of the eight MR imaging evident fractures of anterior process of calcaneus were seen on radiographs. Associated fractures of the talus (n=5), navicular bone (n=3), cuboid (n=2), and calcaneal body (n=1) were noted. Associated injuries to the anterior talofibular ligament (n=3) and tears of the peroneus brevis (n=3) and peroneus longus (n=1) tendons were present. All fractures were treated non-operatively. Two patients had subtalar joint steroid injection for symptomatic relief. Conclusions: Fractures of the anterior process of the calcaneus are uncommon in MR examinations of a general population of patients with foot and ankle symptoms. Although anterior process of calcaneus fractures are rare, there was a moderately high incidence of associated bone and soft-tissue injuries. C1 Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Ouellette, H (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Radiol, 55 Fruit St,Yawkey 6046, Boston, MA 02114 USA. EM haouellette@partners.org NR 13 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD NOV PY 2006 VL 35 IS 11 BP 833 EP 837 DI 10.1007/s00256-006-0154-9 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 097NX UT WOS:000241455800006 PM 16724199 ER PT J AU Thomas, RJ Kwong, K AF Thomas, Robert Joseph Kwong, Kenneth TI Modafinil activates cortical and subcortical sites in the sleep-deprived state SO SLEEP LA English DT Article DE sleep deprivation; modafinil; functional magnetic resonance; working memory ID DOPAMINE-RECEPTOR AGONIST; MILD COGNITIVE IMPAIRMENT; REGIONAL BRAIN ACTIVITY; WORKING-MEMORY; PREFRONTAL CORTEX; INTERINDIVIDUAL DIFFERENCES; DIFFERENTIAL VULNERABILITY; INDIVIDUAL-DIFFERENCES; DAYTIME SLEEPINESS; EXECUTIVE FUNCTION AB Subject Objectives: To assess the effect of the wake-promoting drug modafinil on working memory and brain activation in the executive network, following a single night of sleep deprivation. Design: Randomized, placebo-controlled, 4-arm, double-blind evaluation of a single 200-mg dose of modafinil on working memory (1-, 2-, and 3-back)-related functional brain activation and performance following overnight sleep deprivation. Setting: General Clinical Research Center, Biomedical Imaging Center. Subjects: Eight medication-free men, aged 21 to 35 years. Interventions: Overnight sleep deprivation, single-dose 200-mg modafinil, functional magnetic resonance imaging Measurements and Results: Brain activation patterns and regional signal intensity based on the blood-oxygen level-dependent signal were assessed. The following reaction times were used as measures of performance: (1) attention in the scanner before functional scanning, (2) "back" responses during the active-task block, and (3) attention during the base-line task block. Contrast of activation maps among conditions revealed sleep-deprivation and drug effects, and their interactions. Performance in the deprived state was enhanced by modafinil only at an intermediate (2-back) level of task difficulty and was associated with the recruitment of increased cortical activation volumes. Strong and consistent individual differences in performance were noted on the working memory tasks. Conclusions: Modafinil effectively counters the adverse effects of overnight sleep deprivation on working memory but only when task difficulty is moderate, recruiting extensive areas in the executive network to do so. Interindividual differences in working-memory performance are stable trait characteristics. C1 Beth Israel Deaconess Med Ctr, Med Div Pulm Crit Care & Sleep, Boston, MA 02215 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Thomas, RJ (reprint author), Beth Israel Deaconess Med Ctr, Sleep Unit, CC-866,330 Brookline Ave, Boston, MA 02215 USA. EM rthomas1@bidmc.harvard.edu FU NCRR NIH HHS [RR 01032] NR 78 TC 30 Z9 30 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 2006 VL 29 IS 11 BP 1471 EP 1481 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 107OU UT WOS:000242181700021 PM 17162995 ER PT J AU Rehman, SU Hutchison, FN AF Rehman, Shakaib U. Hutchison, Florence N. TI Hypertensive men living in a southern city: Is it a recipe for disaster? SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID BLOOD-PRESSURE CONTROL C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Rehman, SU (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St 11C, Charleston, SC 29401 USA. EM shakaib.rehman@va.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD NOV PY 2006 VL 99 IS 11 BP 1200 EP 1200 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134HA UT WOS:000244072900003 PM 17195408 ER PT J AU Podovei, M Kuo, B AF Podovei, Mihaela Kuo, Braden TI Irritable bowel syndrome: A practical review SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE irritable bowel syndrome; functional bowel disorder; diarrhea; constipation ID FUNCTIONAL GASTROINTESTINAL DISORDERS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; RANDOMIZED CONTROLLED-TRIAL; KAPPA-AGONIST FEDOTOZINE; LACTULOSE BREATH TEST; FOOD INTOLERANCE; ABDOMINAL-PAIN; COLON SYNDROME; SYMPTOM IMPROVEMENT AB The epidemiology and current understanding of the pathophysiology of irritable bowel syndrome is reviewed, beginning with a historical perspective. The roles of genetics, environment, allergy, infection and inflammation, bacterial overgrowth, hormones and motility abnormalities are discussed. Using the current evidence-based literature, the practical approach of diagnosis and treatment is outlined, including traditional modalities and newer therapeutic agents such as serotonin modulators. C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, GI Unit, GRJ 719, Boston, MA 02114 USA. EM bkuo@partners.org NR 128 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD NOV PY 2006 VL 99 IS 11 BP 1235 EP 1242 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 134HA UT WOS:000244072900014 PM 17195419 ER PT J AU Ballantyne, JC AF Ballantyne, Jane C. TI Opioids for chronic nonterminal pain SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE pain; chronic disease; opioids; drug tolerance; addiction; neuroendocrine effects ID CONTROLLED-RELEASE OXYCODONE; PLACEBO-CONTROLLED-TRIAL; CHRONIC NONMALIGNANT PAIN; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CROSSOVER TRIAL; CHRONIC NONCANCER PAIN; PHANTOM LIMB PAIN; LONG-TERM USE; DOUBLE-BLIND; NEUROPATHIC PAIN AB This article first reviews the evidence for and against chronic opioid therapy. Evidence supporting the opioid responsiveness of chronic pain, including neuropathic pain, includes multiple randomized trials conducted over months (up to 8 months). Observational studies are conducted for longer, and many also support opioid analgesic efficacy. Concerns have arisen about loss of efficacy with prolonged use, possibly related to tolerance or opioid-induced hyperalgesia. Mechanisms of tolerance and opioid-induced hyperalgesia are explored. Evidence on other important outcomes such as improvement in function and quality of life is mixed, and is less convincing than evidence supporting analgesic efficacy. It is clear from current evidence that many patients abandon chronic opioid therapy because of the unacceptability of side effects. There are also concerns about toxicity, especially when opioids are used in high doses for prolonged periods, related to hormonal and immune function. The issue of addiction during opioid treatment of chronic pain is also explored. Addiction issues present many complex questions that have not been satisfactorily answered. Opioid treatment of pain has been, and remains, severely hampered because of actual and legal constraints related to addiction risk. Pain advocacy has focused on placing addiction risk into context so that addiction fears do not compromise effective treatment of pain. On the other hand, denying addiction risk during opioid treatment of chronic pain has not been helpful in terms of providing physicians with the tools needed for safe chronic opioid therapy. Here, a structured goal-directed approach to chronic opioid treatment is suggested; this aims to select and monitor patients carefully, and wean therapy if treatment goals are not reached. Chronic opioid therapy for pain has not been a universal success since it was re-established during the last two decades of the twentieth century. It is now realized that the therapy is not as effective or as free from addiction risk as was once thought. Knowing this, many ethical dilemmas arise, especially in relation to patients' right to treatment competing with physicians' need to offer the treatment selectively. In the future, we must learn how to select patients for this therapy who are likely to achieve improvement in pain, function and quality of life without interference from addiction. Efforts will also be made in the laboratory to identify opioids with lower abuse potential. C1 Massachusetts Gen Hosp, Pain Ctr, Div Pain Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Pain Ctr, Div Pain Med, Dept Anesthesia & Crit Care, 15 Parkman St,WACC 333, Boston, MA 02114 USA. EM jballantyne@partners.org NR 88 TC 27 Z9 27 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD NOV PY 2006 VL 99 IS 11 BP 1245 EP 1255 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 134HA UT WOS:000244072900015 PM 17195420 ER PT J AU Treff, NR Vincent, RK Budde, ML Browning, VL Magliocca, JF Kapur, V Odorico, JS AF Treff, Nathan R. Vincent, Robert K. Budde, Melisa L. Browning, Victoria L. Magliocca, Joseph F. Kapur, Vivek Odorico, Jon S. TI Differentiation of embryonic stem cells conditionally expressing neurogenin 3 SO STEM CELLS LA English DT Article DE microarray; notch; quantitative reverse transcription; polymerase chain reaction; tanscriptional regulation; embryonic stem cells; pancreatic differentiation ID ISLET DIFFERENTIATION; IN-VITRO; ENDOCRINE; PANCREAS; NOTCH; PROGENITORS; LINEAGES; GENES AB Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. To better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profiles of murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An mESC line was created in order to induce Ngn3 by adding doxycycline to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of contexts, including undifferentiated ESCs and differentiating embryoid bodies (EBs). Genes regulated by Ngn3 in a context-independent manner were identified and analyzed using systematic gene ontology tools. This analysis revealed Notch signaling as the most significantly regulated signaling pathway (p = .009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and, conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitormediated Notch signaling inhibition (p <.0001) when compared with uninduced EBs. Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin expression. C1 Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ Minnesota, Dept Vet Sci, St Paul, MN 55108 USA. Univ Minnesota, Dept Biomed Sci, St Paul, MN 55108 USA. Univ Minnesota, Dept Microbiol, St Paul, MN 55108 USA. WiCell Res Inst, Madison, WI USA. RP Odorico, JS (reprint author), Univ Wisconsin Hosp, N4-756 CSC,600 Highland Ave, Madison, WI 53792 USA. EM jon@surgery.wisc.edu RI Kapur, Vivek/F-7610-2013; OI Kapur, Vivek/0000-0002-9648-0138 FU NIAID NIH HHS [T32 AI52037]; NIDDK NIH HHS [U19-DK061244] NR 27 TC 35 Z9 37 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV PY 2006 VL 24 IS 11 BP 2529 EP 2537 DI 10.1634/stemcells.2006-0082 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 103NM UT WOS:000241893600023 PM 16809427 ER PT J AU Viswanathan, A Gray, F Bousser, MG Baudrimont, M Chabriat, H AF Viswanathan, Anand Gray, Francoise Bousser, Marie-Germaine Baudrimont, Marielle Chabriat, Hugues TI Cortical neuronal apoptosis in CADASIL SO STROKE LA English DT Article DE apoptosis; CADASIL; cortex; cortical atrophy; lacunar infarction; white matter damage ID ISCHEMIC VASCULAR-DISEASE; ALZHEIMERS-DISEASE; BRAIN VOLUME; MRI; DOMINANT; STROKE; LEUKOENCEPHALOPATHY; CONNECTIONS; PATTERNS; PROFILE AB Background and Purpose-Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the NOTCH3 gene and is a model of pure vascular dementia. Cortical atrophy has been reported to be associated with cognitive decline in the disease, although the underlying mechanism is unknown. We postulated that apoptosis may be involved in this process. Methods-We report the clinical history, magnetic resonance imaging findings, and pathologic examinations of 4 patients (2 of whom were demented) who died from complications of the disease. Apoptosis was evaluated in brain tissue using antibodies against activated caspase3 and in situ end labeling assays for DNA fragmentation. Results-Widespread neuronal apoptosis in the cerebral cortex (predominantly in layers 3 and 5) was observed in all patients. This was not seen in 3 non-CADASIL controls. Semiquantitative analysis suggested that apoptosis was more extensive in the presence of larger load of subcortical ischemic lesions and smaller brain volumes. Conclusions-Neuronal apoptosis may be involved in cortical atrophy in CADASIL and appears related to the burden of subcortical ischemic lesions. These findings may have important implications in other small vessel diseases and may provide a potential target for future therapeutic interventions. C1 Univ Paris 07, AP HP, Hop Lariboisiere, Dept Neuropathol, F-75010 Paris, France. Univ Paris 07, AP HP, Hop Lariboisiere, Dept Neurol, F-75010 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 02114 USA. RP Gray, F (reprint author), Univ Paris 07, AP HP, Hop Lariboisiere, Dept Neuropathol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM francoise.gray@lrb.ap-hop-paris.fr RI Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 35 TC 56 Z9 56 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2006 VL 37 IS 11 BP 2690 EP 2695 DI 10.1161/01.STR.0000245091.28429.6a PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 102GK UT WOS:000241798800018 PM 17008611 ER PT J AU Earnshaw, SR Joshi, AV Wilson, MR Rosand, J AF Earnshaw, Stephanie R. Joshi, Ashish V. Wilson, Michele R. Rosand, Jonathan TI Cost-effectiveness of recombinant activated factor VII in the treatment of intracerebral hemorrhage SO STROKE LA English DT Article DE cost-effectiveness analysis; economics; intracerebral hemorrhage; stroke management ID ACUTE ISCHEMIC-STROKE; UNITED-STATES; MODEL; CARE; LENGTH; TRIAL; STAY; LIFE AB Background and Purpose-Intracerebral hemorrhage (ICH) is among the most costly and debilitating forms of stroke. Results from a recent Phase IIb clinical trial demonstrate that administration of recombinant activated factor VII (rFVIIa) reduces ICH mortality and improves functional outcome. In the current analysis, we examine the cost-effectiveness of early treatment with rFVIIa for ICH in the United States. Methods-A decision-analytic model was developed to estimate the lifetime costs and outcomes associated with rFVIIa treatment at doses of 40, 80 and 160 mu g/kg compared with current standard of care in treating ICH, from a US third-party payer perspective. The patient population was similar to that of the Phase IIb clinical trial. Model structure and inputs were obtained from published literature, clinical trial data, claims databases, and expert opinion. All costs are presented in 2005 US dollars. Outcomes included incremental cost per life-year (LY) saved and incremental cost per quality-adjusted life-year (QALY) gained. Costs and outcomes were discounted at 3% annually. Univariate and multivariate sensitivity analyses were conducted to assess model robustness. Results-Compared with standard care, treatment with rFVIIa 40 mu g/kg, and 160 mu g/kg results in total lifetime cost-effectiveness ratios of $6308/QALY and $3152/QALY, respectively. Treatment with rFVIIa 80 mu g/kg was found to be cost saving and a gain of 1.67 QALYs is achieved over a patient's lifetime. These results are robust to changes in input parameters. Conclusions-Treatment of ICH with rFVIIa 40 mu g/kg and 160 mu g/kg appears to be cost-effective (<=$50000/QALY). At the 80 mu g/kg dose, rFVIIa was not only cost-effective, but also cost saving. C1 Novo Nordisk Inc, Princeton, NJ USA. RTI Hlth Solut, Res Triangle Pk, NC USA. Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Earnshaw, SR (reprint author), 200 Pk Off Dr,POB 12194, Res Triangle Pk, NC 27709 USA. EM searnshaw@rti.org NR 29 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2006 VL 37 IS 11 BP 2751 EP 2758 DI 10.1161/01.STR.0000246611.21999.5d PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 102GK UT WOS:000241798800028 PM 17008607 ER PT J AU Springer, TA AF Springer, Timothy A. TI Complement and the multifaceted functions of VWA and integrin I domains SO STRUCTURE LA English DT Review ID FACTOR A1 DOMAIN; CRYSTAL-STRUCTURE; FACTOR-B; BINDING-SITE; GLYCOPROTEIN IB; ANTHRAX TOXIN; INSIGHTS; REVEALS; CONFORMATION; CONVERTASE AB The recent crystal structure of complement protein component C2a reveals an interface between its VWA and serine protease domains that could not exist in the zymogen C2. The implied change in VWA domain conformation between C2 and C2a differs from that described for other VWA domains, including the I domains in integrins. Here, the remarkable diversity in both conformational regulation and ligand binding among VWA domains that function in complement, hemostasis, cell adhesion, anthrax toxin binding, vesicle transport, DNA break repair, and RNA quality control is reviewed. Finally, implications for metastability of complement convertases are discussed. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu FU NCI NIH HHS [CA31799, R37 CA031798, R01 CA031799]; NHLBI NIH HHS [P01 HL048675, HL48675]; NIAID NIH HHS [AI72765, R01 AI072765] NR 22 TC 45 Z9 45 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV PY 2006 VL 14 IS 11 BP 1611 EP 1616 DI 10.1016/j.str.2006.10.001 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 106UQ UT WOS:000242127800004 PM 17098186 ER PT J AU Patchell, RA Regine, WF Renschler, M Loeffler, JS Sawaya, R Chin, LS Andrews, DW AF Patchell, Roy A. Regine, William F. Renschler, Markus Loeffler, Jay S. Sawaya, Raymond Chin, Lawrence S. Andrews, David W. TI Comments about the prospective randomized trial by Aoyama et al SO SURGICAL NEUROLOGY LA English DT Editorial Material ID BRAIN RADIATION-THERAPY; STEREOTACTIC RADIOSURGERY; SINGLE METASTASES; RADIOTHERAPY C1 Univ Kentucky, Med Ctr, Div Neurosurg, Lexington, KY 40536 USA. Univ Maryland, Dept Radiat Oncol, Baltimore, MD 21201 USA. Pharmacycl Inc, Clin Dev, Sunnyvale, CA 94085 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Boston Univ, Sch Med, Dept Neurol Surg, Boston, MA 02118 USA. Thomas Jefferson Univ, Dept Neurol Surg, Philadelphia, PA 19107 USA. RP Patchell, RA (reprint author), Univ Kentucky, Med Ctr, Div Neurosurg, Lexington, KY 40536 USA. EM david.andrews@jefferson.edu NR 6 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD NOV PY 2006 VL 66 IS 5 BP 459 EP 460 DI 10.1016/j.surneu.2006.08.003 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 106UA UT WOS:000242126000003 PM 17084184 ER PT J AU Drenser, K Sarraf, D Jain, A Small, KW AF Drenser, Kimberly Sarraf, David Jain, Atul Small, Kent W. TI Crystalline retinopathies SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE crystalline maculopathy; crystalline retinopathy; refractile retinal deposits; retinal crystals ID SJOGREN-LARSSON-SYNDROME; JUXTAFOVEOLAR RETINAL TELANGIECTASIS; FATTY ALDEHYDE DEHYDROGENASE; EXPERIMENTAL CAROTENOID RETINOPATHY; HYPEROXALURIA TYPE-I; TALC RETINOPATHY; NEPHROPATHIC CYSTINOSIS; ISCHEMIC RETINOPATHY; MACULAR DEGENERATION; KJELLINS-SYNDROME AB Man), types of crystalline retinopathies have been described, associated with a myriad of medical conditions ranging from chronic retinal conditions to inherited systemic diseases. This comprehensive review summarizes the different types of crystalline retinopathics, including their clinical presentations, diagnostic criteria, pathology, and treatment options. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Sch Med, Los Angeles, CA 90095 USA. Associated Retinal Consultants, Royal Oak, MI USA. Greater Los Angeles Vet Adm Healthcare Ctr, Los Angeles, CA USA. King Drew Med Ctr, Los Angeles, CA USA. Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA. Cedars Sinai Med Towers, Macula & Retina Ctr, Mol Insight LLC, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Sch Med, 100 Stein Plaza, Los Angeles, CA 90095 USA. NR 108 TC 19 Z9 19 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 2006 VL 51 IS 6 BP 535 EP 549 DI 10.1016/j.survophthal.2006.08.006 PG 15 WC Ophthalmology SC Ophthalmology GA 104SS UT WOS:000241980000001 PM 17134644 ER PT J AU Altfeld, M Allen, TM AF Altfeld, Marcus Allen, Todd M. TI Hitting HIV where it hurts: an alternative approach to HIV vaccine design SO TRENDS IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; CLASS-I MOLECULE; STRUCTURALLY CONSTRAINED EPITOPE; LYMPHOCYTE ESCAPE MUTATION; SIMIAN IMMUNODEFICIENCY; VIRAL LOAD; IMMUNE-RESPONSES; RHESUS-MONKEYS; ANTIRETROVIRAL THERAPY AB The ability of HIV-1 to mutate represents a major challenge to current vaccine approaches. However, some individuals achieving control of HIV during natural infection seem unique in their dominant targeting by cellular immune responses of conserved regions of HIV that, if mutated, exact a substantial impact on viral replicative capacity, or fitness. Notably, the partial suppression of HIV in treated individuals harboring viruses with drug-resistant mutations has also been linked to impaired viral fitness. The convergence of these observations suggests that vaccines designed to focus immune responses narrowly against regions of HIV susceptible to highly deleterious mutations might prove effective in controlling viral replication to levels that slow disease progression and reduce transmission. Therefore, it will be crucial to identify these 'Achilles heels' of HIV that might represent uniquely susceptible targets, and test whether vaccine constructs enabling specific targeting of CD8(+) T-cell responses against such regions would enable the control of HIV and SIV. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Infect Dis Unit, Boston, MA 02129 USA. EM maltfeld@partners.org; tallen2@partners.org RI Allen, Todd/F-5473-2011 NR 80 TC 65 Z9 67 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD NOV PY 2006 VL 27 IS 11 BP 504 EP 510 DI 10.1016/j.it.2006.09.007 PG 7 WC Immunology SC Immunology GA 104DW UT WOS:000241937400003 PM 16997629 ER PT J AU Schwarzschild, MA Agnati, L Fuxe, K Chen, JF Morelli, M AF Schwarzschild, Michael A. Agnati, Luigi Fuxe, Kjell Chen, Jiang-Fan Morelli, Micaela TI Targeting adenosine A(2A) receptors in Parkinson's disease SO TRENDS IN NEUROSCIENCES LA English DT Review ID C-FOS EXPRESSION; BIOLUMINESCENCE ENERGY-TRANSFER; DOPA-INDUCED DYSKINESIA; CENTRAL-NERVOUS-SYSTEM; 6-HYDROXYDOPAMINE-LESIONED RATS; DOPAMINE-D-2 RECEPTORS; TURNING BEHAVIOR; GLOBUS-PALLIDUS; BINDING CHARACTERISTICS; SYNERGISTIC INTERACTION AB The adenosine A(2A) receptor has emerged as an attractive non-dopaminergic target in the pursuit of improved therapy for Parkinson's disease (PD), based in part on its unique CNS distribution. It is highly enriched in striatopallidal neurons and can form functional heteromeric complexes with other G-protein-coupled receptors, including dopamine D-2, metabotropic glutamate mGlu(5) and adenosine A(1) receptors. Blockade of the adenosine A(2A) receptor in striatopallidal neurons reduces postsynaptic effects of dopamine depletion, and in turn lessens the motor deficits of PD. A(2A) antagonists might partially improve not only the symptoms of PD but also its course, by slowing the underlying neurodegeneration and reducing the maladaptive neuroplasticity that complicates standard 'dopamine replacement' treatments. Thus, we review here a prime example of translational neuroscience, through which antagonism of A(2A) receptors has now entered the arena of clinical trials with realistic prospects for advancing PD therapeutics. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. EM michaels@helix.mgh.harvard.edu OI morelli, micaela/0000-0003-0394-5782 FU NIEHS NIH HHS [ES10804]; NINDS NIH HHS [NS54978] NR 75 TC 254 Z9 256 U1 0 U2 13 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 2006 VL 29 IS 11 BP 647 EP 654 DI 10.1016/j.tins.2006.09.004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 109FX UT WOS:000242294400008 PM 17030429 ER PT J AU Nakabayashi, M Beard, C Kelly, SM Carr-Locke, DL Oh, WK AF Nakabayashi, Mari Beard, Clair Kelly, Sandra M. Carr-Locke, David L. Oh, William K. TI Treatment of a radiation-induced rectal ulcer with hyperbaric oxygen therapy in a man with prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE rectal ulcer; proctopathy; radiation therapy; hyperbaric oxygen therapy; prostate cancer ID TREATMENT RELATED MORBIDITY; DOUBLE-BLIND; RADIOTHERAPEUTIC PARAMETERS; 5-AMINOSALICYLIC ACID; CLINICAL-TRIAL; ONCOLOGY-GROUP; PROCTITIS; TOXICITY; SUCRALFATE; PREVENTION AB Late radiation proctopathy is a painful and vexing complication of prostate radiation. We report a case of a 55-year-old man with prostate cancer, and complaints of tenesmus and severe rectal pain after radiation therapy. The patient was diagnosed with a locally advanced Gleason score 8 prostate cancer and an increased prostate-specific antigen of 42.3 ng/ml. His past medical history was notable for a history of bilateral lymph node dissection complicated by Clostridium difficile colitis. He subsequently received 3-dimensional conformal radiation therapy. Seven months after completing therapy, minor rectal bleeding and significant pain developed, requiring increasing doses of opioid analgesics. Fourteen months after 3-dimensional conformal radiation therapy, sigmoidoscopy revealed a single chronic deep ulcer at the anorectal junction. As an alternative to diverting colostomy, the patient underwent a course of hyperbaric oxygen. Within I month of completing hyperbaric oxygen treatment, his symptoms completely resolved. Nine months from completion of hyperbaric oxygen therapy, he has had no recurrence of symptoms. Hyperbaric oxygen therapy can be considered a treatment option after failure of standard treatments in patients with severe radiation proctopathy. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 37 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2006 VL 24 IS 6 BP 503 EP 508 DI 10.1016/j.urolonc.2006.02.002 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 116RW UT WOS:000242821000006 PM 17138131 ER PT J AU Habib, MJ Lawson, K Summers, KK Eakin, RT Barner, J Brown, C Shepherd, MD AF Habib, M. J. Lawson, K. Summers, K. K. Eakin, R. T. Barner, J. Brown, C. Shepherd, M. D. TI Relationship between adherence to antiretroviral therapy and the cost-effectiveness of antiretroviral therapy SO VALUE IN HEALTH LA English DT Meeting Abstract C1 i3 Innovus, Burlington, ON, Canada. Univ Texas, Austin, TX 78712 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP A206 EP A206 DI 10.1016/S1098-3015(10)63213-5 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000066 ER PT J AU Hay, JW Scranton, R Yucel, K Guo, A Balzer, T Gaziano, J AF Hay, J. W. Scranton, R. Yucel, K. Guo, A. Balzer, T. Gaziano, J. TI Cost impact of diagnostic imaging for lower extremity peripheral vascular disease (PVD) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA USA. Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA USA. Berlex Labs Inc, Wayne, NJ 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP A343 EP A343 DI 10.1016/S1098-3015(10)63638-8 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000491 ER PT J AU Rahilly, CR Gaziano, J Scranton, R AF Rahilly, C. R. Gaziano, J. Scranton, R. TI Effect of absolute reduction in LDL cholesterol on cardiovascular events: Does final LDL cholesterol acheived matter? SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Boston VA Hlth Care Syst, Jamaica Plain, MA USA. Harvard Univ, Sch Med, VA Boston Hlth Care Syst, 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP A340 EP A341 DI 10.1016/S1098-3015(10)63629-7 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000482 ER PT J AU Scranton, R Dhingra, R Lawler, E Hay, JW Yucel, K Guo, A Balzer, T Gaziano, J AF Scranton, R. Dhingra, R. Lawler, E. Hay, J. W. Yucel, K. Guo, A. Balzer, T. Gaziano, J. TI Clinical impact of diagnostic imaging of lower extremity peripheral vascular disease SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA USA. Univ So Calif, Los Angeles, CA USA. Berlex Labs Inc, Wayne, NJ 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 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP A337 EP A337 DI 10.1016/S1098-3015(10)63618-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000471 ER PT J AU Albadawi, H Crawford, RS Atkins, MD Watkins, MT AF Albadawi, Hassan Crawford, Robert S. Atkins, Marvin D. Watkins, Michael T. TI Role of poly(ADP-ribose) polymerase during vascular reconstruction SO VASCULAR LA English DT Article DE inflammation; ischemia; reperfusion AB Open vascular repair of ischemic myocardium and aortic aneurysms results in a systemic inflammatory response that influences the mortality and morbidity of these procedures. Recent studies in animal models of complex vascular reconstruction indicate that the activity of poly(ADP-ribose) polymerase (PARP) may influence the mortality and morbidity of these kinds of reconstructions. PARP's activity, localized to nuclei and mitochondria, is stimulated by deoxyribonucleic acid (DNA) strand breaks. Activation of PARP results in synthesis of poly(ADP-ribose) sugar moieties, whose primary role is to protect DNA from degradation during cytotoxic stress. Paradoxically, when stressful conditions similar to those experienced during vascular reconstructions result in overactivation of PARP, depletion of cellular levels of adenosine triphosphate and nicotinamide adenine dinucleotide can result in exacerbation of tissue injury. Herein we review the role of PARP in inflammation and its relevance to cardiovascular reconstructions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 31 TC 2 Z9 2 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 1708-5381 J9 VASCULAR JI Vascular PD NOV-DEC PY 2006 VL 14 IS 6 BP 362 EP 365 DI 10.2310/6670.2006.00061 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V44FZ UT WOS:000202989900007 PM 17150157 ER PT J AU Isayama, T Chen, Y Kono, M Degrip, WJ Ma, JX Crouch, RK AF Isayama, T. Chen, Y. Kono, M. Degrip, W. J. Ma, J. X. Crouch, R. K. TI Differences in the pharmacological activation of visual opsins SO VISUAL NEUROSCIENCE LA English DT Article DE rod; cone; rhodopsin; transducin; phototransduction ID COUPLED RECEPTOR KINASE; PROTEIN BETA-SUBUNIT; CONE PHOTORECEPTORS; SALAMANDER RODS; VERTEBRATE PHOTORECEPTORS; PALMITOYLATION SITES; MOLECULAR-CLONING; RETINAL CONES; GAMMA-SUBUNIT; BINDING-SITE AB Opsins, like many other G-protein-coupled receptors, sustain constitutive activity in the absence of ligand. In partially bleached rods and cones, opsin's activity closes cGMP-gated channels and produces a state of "pigment adaptation" with reduced sensitivity to light and accelerated flash response kinetics. The truncated retinal analogue, beta-ionone, further desensitizes partially bleached green-sensitive salamander rods, but enables partially bleached red-sensitive cones to recover dark-adapted physiology. Structural differences between rod and cone opsins were proposed to explain the effect. Rods and cones, however, also contain different transducins, raising the possibility that G-protein type determines the photoreceptor-specific effects of beta-ionone. To test the two hypotheses, we applied beta-ionone to partially bleached blue-sensitive rods and cones of salamander, two cells that couple the same cone-like opsin to either rod or cone transducin, respectively. Immunocytochemistry confirmed that all salamander rods contain one form of transducin, whereas all cones contain another. beta-Ionone enhanced pigment adaptation in blue-sensitive rods, but it also did so in blue- and UV-sensitive cones. Furthermore, all recombinant salamander rod and cone opsins, with the exception of the red-sensitive cone opsin, activated rod transducin upon the addition of beta-ionone. Thus opsin structure determines the identity of beta-ionone as an agonist or an inverse agonist and in that respect distinguishes the red-sensitive cone opsin from all others. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA. Med Univ S Carolina, Dept Ophthalmol, Storm Eye Res Inst, Charleston, SC 29425 USA. Univ Nijmegen, Dept Biochem, NCMLS, Nijmegen, Netherlands. RP Isayama, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM tomoki_isayama@meei.harvard.edu RI Grip, W.J./L-4335-2015; OI Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [EY014793, EY11358, EY15650, EY12231, EY04939, EY013748, EY014104] NR 50 TC 16 Z9 16 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD NOV-DEC PY 2006 VL 23 IS 6 BP 899 EP 908 DI 10.1017/S0952523806230256 PG 10 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 137EK UT WOS:000244275600007 PM 17266782 ER PT J AU Steere, AC AF Steere, Allen C. TI Lyme borreliosis in 2005, 30 years after initial observations in Lyme Connecticut SO WIENER KLINISCHE WOCHENSCHRIFT LA English DT Review DE Lyme borreliosis; epidemiology; pathogenesis; diagnosis; therapy ID BURGDORFERI SENSU-STRICTO; SURFACE PROTEIN-A; LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE CHAIN-REACTION; ERYTHEMA MIGRANS; DISEASE SPIROCHETE; HOST-DEFENSE; COST-EFFECTIVENESS; ARTHRITIS; MICE AB Nearly 100 years ago, Afzelius described a patient with an expanding skin lesion, called erythema migrans [1], which is now known to be the initial skin manifestation of Lyme borreliosis. Approximately 70 years later, in 1976, epidemiologic evaluation of a cluster of children with arthritis in Lyme, Connecticut [2] led to a complete description of the infection [3]. During the subsequent years, investigators in a number of countries have made remarkable strides in the elucidation of this tick-borne spirochetal infection, The purpose of this review is to discuss the current status of Lyme borreliosis, including areas in which knowledge of the infection is still incomplete. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammat Dis, Boston, MA USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA. EM asteere@partners.org NR 84 TC 36 Z9 41 U1 0 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0043-5325 J9 WIEN KLIN WOCHENSCHR JI Wien. Klin. Wochen. PD NOV PY 2006 VL 118 IS 21-22 BP 625 EP 633 DI 10.1007/s00508-006-0687-x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 126FN UT WOS:000243497900002 PM 17160599 ER PT J AU Saksena, MA Dahl, DM Harisinghani, MG AF Saksena, Mansi A. Dahl, Douglas M. Harisinghani, Mukesh G. TI New imaging modalities in bladder cancer SO WORLD JOURNAL OF UROLOGY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASES; VIRTUAL CYSTOSCOPY; URINARY-BLADDER; MR LYMPHANGIOGRAPHY; PROSTATE-CANCER; CT CYSTOGRAPHY; TUMORS; ENHANCEMENT C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Saksena, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. EM mansisaksena@gmail.com NR 47 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD NOV PY 2006 VL 24 IS 5 BP 473 EP 480 DI 10.1007/s00345-006-0118-7 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 107EW UT WOS:000242154500002 PM 17102950 ER PT J AU Efstathiou, JA Zietman, AL Kaufman, DS Heney, NM Coen, JJ Shipley, WU AF Efstathiou, Jason A. Zietman, Anthony L. Kaufman, Donald S. Heney, Niall M. Coen, John J. Shipley, William U. TI Bladder-sparing approaches to invasive disease SO WORLD JOURNAL OF UROLOGY LA English DT Article DE bladder cancer; radiation therapy; chemotherapy; radical cystectomy; trimodality therapy; organ preservation ID TRANSITIONAL-CELL-CARCINOMA; QUALITY-OF-LIFE; THERAPY-ONCOLOGY-GROUP; PHASE-II TRIAL; SELECTIVE ORGAN PRESERVATION; COMBINED-MODALITY TREATMENT; GEMCITABINE PLUS CISPLATIN; RADICAL CYSTECTOMY; NEOADJUVANT CHEMOTHERAPY; TRANSURETHRAL RESECTION AB Although immediate radical cystectomy remains the standard of care for invasive bladder cancer, a large body of international experience from single institutions and cooperative groups has accumulated, suggesting favorable results with bladder-sparing approaches in appropriately selected patients. Modern selective bladder preservation with trimodality therapy, consisting of transurethral resection of the bladder tumor, radiation, and chemotherapy, can achieve complete response rates of 60-80%, 5-year survival rates of 50-60%, and survival rates with an intact bladder of 40-45%. Although no randomized comparisons between cystectomy and trimodality therapy exist, long-term data confirm that the 10-year overall and disease-specific survival rates for patients in bladder-sparing protocols are comparable to outcomes reported in contemporary cystectomy series. In addition, quality of life studies have demonstrated that the retained native bladder functions well. Thus, trimodality therapy with careful cystoscopic surveillance and with prompt cystectomy for invasive recurrences has emerged as a legitimate alternative to extirpative surgery. Future work will continue to optimize the bladder-sparing regimen while limiting toxicity. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 77 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD NOV PY 2006 VL 24 IS 5 BP 517 EP 529 DI 10.1007/s00345-006-0114-y PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 107EW UT WOS:000242154500007 PM 17082940 ER PT J AU Cheruvu, PK Finn, AV Gardner, C Caplan, J Goldstein, JA Stone, GW Virmani, R Path, CV Muller, JE AF Cheruvu, Pavan K. Finn, Aloke V. Gardner, Craig Caplan, Jay Goldstein, James A. Stone, Gregg W. Virmani, Renu Path, C. V. Muller, James E. TI Density and distribution of thin-cap fibroatheroma and ruptured plaque in human coronary arteries - A pathologic study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. InfraReDx Inc, Burlington, MA USA. William Beaumont Hosp, Detroit, MI USA. Lenox Hill Hosp, New York, NY 10021 USA. Cardiovasc Res Fdn, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 22 EP 22 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800121 ER PT J AU Rask-Madsen, C Della Vecchia, K Wu, IH Scott, JA Arikawa, E Matsumoto, M Sotiropoulos, KB Kahn, CR King, GL AF Rask-Madsen, Christian Della Vecchia, Kim Wu, I-Hsien Scott, Joshua A. Arikawa, Emi Matsumoto, Motonobu Sotiropoulos, Konstantinos B. Kahn, C. R. King, George L. TI Loss of insulin signaling in vascular endothelium accelerates atherosclerosis in apolipoprotein e knockout mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 24 EP 24 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800130 ER PT J AU Ahluwalia, N Lin, AY Shen, DX Lin, CY Sinha, S Luster, AD Gerszten, RE AF Ahluwalia, Neil Lin, Alexander Y. Shen, Dongxiao Lin, Christina Y. Sinha, Sumita Luster, Andrew D. Gerszten, Robert E. TI BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Cardiol Div, Charlestown, MA USA. Massachusetts Gen Hosp, Cntr Immunol & Inflammatory Dis, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 39 EP 39 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800200 ER PT J AU Lin, AY Ahluwalia, N Shen, DX Lin, CY Sinha, S Luster, AD Gerszten, RE AF Lin, Alexander Y. Ahluwalia, Neil Shen, Dongxiao Lin, Christina Y. Sinha, Sumita Luster, Andrew D. Gerszten, Robert E. TI Deletion of the T cell chemokine CXCL10 promotes aortic aneurysm formation and rupture SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Cardiol Div, Charlestown, MA USA. Massachusetts Gen Hosp, Cntr Immunol & Inflammatory Dis, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 39 EP 39 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800201 ER PT J AU Oikawa, M Yuan, C Underhill, H Chu, B Yu, W Ferguson, MS Hatsukami, TS AF Oikawa, Minako Yuan, Chun Underhill, Hunter Chu, Baocheng Yu, Wei Ferguson, Marina S. Hatsukami, Thomas S. TI The association of carotid artery plaque calcification and fibrous cap status: A high-resolution magnetic resonance imaging study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. VA Puget Sound HCS, Dept Surg, Seattle, WA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 40 EP 40 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800204 ER PT J AU Kathiresan, S Yang, Q Larson, MG Tofler, GH O'Donnell, CJ AF Kathiresan, Sekar Yang, Qiong Larson, Martin G. Tofler, Geoffrey H. O'Donnell, Christopher J. CA Framingham 100K Steering Committee TI A genome-wide association study to identify common sequence variants related to five circulating hemostatic factor proteins: The framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. RI Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 56 EP 56 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800272 ER PT J AU Leopold, JA Maron, BA Handy, D Stanson, RC Pitt, B Loscalzo, J AF Leopold, Jane A. Maron, Bradley A. Handy, Diane Stanson, Robert C. Pitt, Bertram Loscalzo, Joseph TI Aldosterone antagonism restores vascular reactivity by increasing glucose-6-phosphate dehydrogenase activity SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 68 EP 68 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800328 ER PT J AU Sawada, N Salomone, S Kim, HH Liao, JK AF Sawada, Naoki Salomone, Salvatore Kim, Hyung-Hwan Liao, James K. TI Worsening of endothelial function in mice with endothelial-specific haploinsufficiency of Rac1 SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Vasc Med Bwh, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 68 EP 68 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800330 ER PT J AU Noma, K Oyama, N Kim, HH Salomone, S Moskowitz, MA Liao, JK AF Noma, Kensuke Oyama, Naotsugu Kim, Hyung-Hwan Salomone, Salvatore Moskowitz, Michael A. Liao, James K. TI ROCK2, but not ROCK1, mediates no-dependent neuroprotective effects following transient focal cerebral ischemia SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 74 EP 74 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800357 ER PT J AU Yu, PB Deng, DY Beppu, H Kawai, N Ichinose, F Bloch, KD AF Yu, Paul B. Deng, Donna Y. Beppu, Hideyuki Kawai, Noriko Ichinose, Fumito Bloch, Kenneth D. TI Bone morphogenetic protein (BMP) type II receptor, but not activin type II receptor, mediates the anti-proliferative effects of BMPs in pulmonary artery smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 81 EP 81 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800391 ER PT J AU Colston, JT Chandrasekar, B de la Rosa, SD Freeman, GL Murphy, AL AF Colston, James T. Chandrasekar, Bysani de la Rosa, Sam D. Freeman, Gregory L. Murphy, Audie L. TI Wnt-induced secreted protein-1 is a pro-hypertrophic and pro-fibrotic growth factor SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Texas, HSC, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 86 EP 86 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800416 ER PT J AU Iyer, V Hajjar, RJ Armoundas, AA AF Iyer, Vivek Hajjar, Roger J. Armoundas, Antonis A. TI Catecholaminergic polymorphic ventricular tachycardia - a link between mutation and arrhythmia SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 91 EP 91 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800437 ER PT J AU Bodyak, N Ayus, JC Shivalingappa, V Rigor, D Chen, YS Ke, O Karumanchi, A Thadhani, R Kang, PM AF Bodyak, Natalya Ayus, Juan Carlos Shivalingappa, Venkatesha Rigor, Debra Chen, Yee-Shiuan Ke, Quingen Karumanchi, Ananth Thadhani, Ravi Kang, Peter M. TI Activated vitamin D attenuates left ventricular hypertrophy and dysfunction in DAHL salt-sensitive rats SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 94 EP 94 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800452 ER PT J AU Buys, ES Raher, MJ Passeri, JJ Ichinose, F Picard, MH Sips, PY Brouckaert, P Scherrer-Crosbie, M Bloch, KD AF Buys, Emmanuel S. Raher, Michael J. Passeri, Jonathan J. Ichinose, Fumito Picard, Michael H. Sips, Patrick Y. Brouckaert, Peter Scherrer-Crosbie, Marielle Bloch, Kenneth D. TI Hypertension and cardiac dysfunction in male mice deficient in the alpha 1 subunit of soluble guanylate cyclase SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ghent Univ Flanders, InterUniv, Inst Biotechnol, Ghent, Belgium. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 106 EP 106 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800507 ER PT J AU Zhu, Y Dinesh, D Wecker, A Poh, KK Lu, P Thorne, T Hamada, H Liu, D Tang, Y Kishore, R Losordo, DW Oin, G AF Zhu, Yan Dinesh, Deepika Wecker, Andrea Poh, Kian Keong Lu, Ping Thorne, Tina Hamada, Hiromichi Liu, Dongxu Tang, Yaoliang Kishore, Raj Losordo, Douglas W. Oin, Gangjian TI Isoform-specific dysregulation of Endothelin Converting Enzyme-1 and hypertension in E2F2-deficient mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 St elizabeth Med Cntr, Boston, MA USA. Harvard Univ, Sch Med, CBR Inst BioMed Rsch, Boston, MA USA. Keck Grad Inst, Claremont, 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 107 EP 107 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800512 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI Certain anti-hypertensive agents reduce beta-amyloid neuropathology and improve cognition in a mouse model of Alzheimer's disease. SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Mt Sinai Sch Med, Dept Med, New York, NY USA. VA Med Ctr, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 129 EP 129 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800614 ER PT J AU Shin, JT Ronco, A Bloch, KD MacRae, CA AF Shin, Jordan T. Ronco, Amy Bloch, Kenneth D. MacRae, Calum A. TI Zebrafish BMPR2 is required for normal vasculogenesis and vessel patterning during angiogenesis in vivo SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 140 EP 140 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800666 ER PT J AU Fukata, M Ishikawa, F Nakamura, R Shimazu, H Shimoda, K Nakamura, Y Nakaji, G Ito, H Kaji, Y Akashi, K Shultz, LD Harada, M AF Fukata, Mitsuhiro Ishikawa, Fumihiko Nakamura, Ryu Shimazu, Hideki Shimoda, Kazuya Nakamura, Yobun Nakaji, Gen Ito, Hiroyuki Kaji, Yoshikazu Akashi, Koichi Shultz, Leonard D. Harada, Mine TI Highly purified hematopoietic stem cells generate cardiomyocytes via myeloid progenitors through cell fusion SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Kyushu Univ, Grad Sch Med Sci, Fukuoka 812, Japan. RIKEN, Ctr Allergy & Immunol, Yokohama, Kanagawa, Japan. Carl Zeiss Japan, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 910 BP 164 EP 164 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801088 ER PT J AU Ly, HQ Hoshino, K Pomerantseva, I Yoneyama, R Kawase, Y Takewa, Y T Lau, G De Grand, AM Vacanti, JP Frangioni, JV Hajjar, RJ AF Ly, Hung Q. Hoshino, Kozo Pomerantseva, Irina Yoneyama, Ryuichi Kawase, Yoshiaki Takewa, Yoshiaki T Lau, George De Grand, Alec M. Vacanti, Joseph P. Frangioni, John V. Hajjar, Roger J. TI In vivo assessment of mesenchymal stem cells fate following intracoronary delivery SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 MA 943 BP 171 EP 171 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801121 ER PT J AU Leopold, JA Maron, BA Handy, D Stanton, RC Pitt, B Loscalzo, J AF Leopold, Jane A. Maron, Bradley A. Handy, Diane Stanton, Robert C. Pitt, Bertram Loscalzo, Joseph TI Aldosterone decreases glucose-6-phosphate dehydrogenase expression in vascular endothelial cells by increased expression of cyclic AMP response element modulator SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Michigan, Ann Arbor, MI 48109 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 974 BP 177 EP 178 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801152 ER PT J AU Shen, D Liu, E Sinha, S Heller, EA Dedhar, S Parmacek, MS Lepore, JJ Gerszten, RE AF shen, Dongxiao Liu, Emerson Sinha, Sumita Heller, Eric A. Dedhar, Shoukat Parmacek, Michael S. Lepore, John J. Gerszten, Robert E. TI Perinatal mortality following smooth muscle cell-restricted deletion of integrin-linked kinase SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Univ British Columbia, British Columbia Canc Res Ctr, Vancouver, BC, Canada. Univ Penn, Mol Cardiol Rsch Ctr, Philadelphia, PA 19104 USA. Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1002 BP 183 EP 183 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801180 ER PT J AU Hong, CC Peterson, QP Hong, JY Peterson, RT AF Hong, Charles C. Peterson, Quinn P. Hong, Ji-Young Peterson, Randall T. TI Opposing effects of phosphatidyl inositol-3 kinase and ERK/MAP kinase signaling pathways on artery-vein specification. SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1034 BP 190 EP 190 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801211 ER PT J AU Heuser, A Plovie, ER Ellinor, PT Grossmann, KS Sasse-Klaassen, S Thierfelder, L MacRae, CA Gerull, B AF Heuser, Amd Plovie, Eva R. Ellinor, Patrick T. Grossmann, Katja S. Sasse-Klaassen, Sabine Thierfelder, Ludwig MacRae, Calum A. Gerull, Brenda TI Mutant desmocollin-2 Causes Arrhythmogenic right ventricular cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Max Delbruck Ctr Mol Med, Cardiac Arrythmia Serv & Cardiovasc Res Ctr, Berlin, Germany. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1051 BP 193 EP 193 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801228 ER PT J AU Brundert, M Moore, KJ Merkel, M Heeren, J Rinninger, F AF Brundert, May Moore, Kathryn J. Merkel, Martin Heeren, Joerg Rinninger, Franz TI Scavenger receptor CD36 has a role in HDL metabolism in mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Hosp Eppendorf, Hamburg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1205 BP 226 EP 226 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801382 ER PT J AU Milan, DJ Giokas, AC MacRae, CA AF Milan, David J. Giokas, Andrea C. MacRae, Calum A. TI Delta-Notch signaling determines atrioventricular conduction system cell fate SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 232 EP 233 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801413 ER PT J AU Tsoporis, J Huttunen, HJ Izhar, S Parker, TG AF Tsoporis, James Huttunen, Henri J. Izhar, Shehla Parker, Thomas G. TI A central role for p53 and MAP kinase signaling in rage-dependent, S100B-Induced myocyte apoptosis SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 296 EP 296 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802034 ER PT J AU Van Winkle, DM Cao, Z Liu, LJ Packwood, WH Hum, PD AF Van Winkle, Donna M. Cao, Zhiping Liu, Lijuan Packwood, William H. Hum, Patricia D. TI Gender dependence in PI3K/Akt signaling in Met(5)-enkephalin-induced cardioprotection SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 313 EP 313 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802114 ER PT J AU Nishikawa, K Yasuda, T Kusuhara, M Ohsuzu, F Gold, H AF Nishikawa, Kenichiro Yasuda, Tsunehiro Kusuhara, Masatoshi Ohsuzu, Fumitaka Gold, Herman TI Effects of tumor necrosis factor receptors on inflammation-mediated arterial remodeling SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 325 EP 325 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802172 ER PT J AU Nahrendorf, M Jaffer, FA Kelly, K Sosnovik, D Aikawa, E Libby, P Weissleder, R AF Nahrendorf, Matthias Jaffer, Farouc A. Kelly, Kimberly Sosnovik, David Aikawa, Elena Libby, Peter Weissleder, Ralph TI In vivo imaging of anti-atherosclerotic pharmacotherapy with a VCAM-1 targeted multimodal nanoparticle SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Ctr Mol Imaging Rsch, Boston, MA 02114 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Rsch Ctr, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 336 EP 337 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802226 ER PT J AU Jaffer, FA Nahrendorf, M Kohler, RH Aikawa, E Libby, P Weissleder, R AF Jaffer, Farouc A. Nahrendorf, Matthias Kohler, Rainer H. Aikawa, Elena Libby, Peter Weissleder, Ralph TI Statin therapy reduces cysteine protease activity in atherosclerosis in vivo SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 337 EP 337 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802228 ER PT J AU Morishige, K Kacher, D Libby, P Josephson, L Weissleder, R Aikawa, M AF Morishige, Kunio Kacher, Daniel Libby, Peter Josephson, Lee Weissleder, Ralph Aikawa, Masanori TI MRI enhanced with magnetic nanoparticles measures inflammatory burden in atherosclerosis in vivo SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 337 EP 337 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802227 ER PT J AU Pande, AN Jaffer, FA Sosnovik, DE Sun, EY Kelly, KA Aikawa, E Nahrendorf, M Libby, P Weissleder, R AF Pande, Ashvin N. Jaffer, Farouc A. Sosnovik, David E. Sun, Eric Y. Kelly, Kimberly A. Aikawa, Elena Nahrendorf, Matthias Libby, Peter Weissleder, Ralph TI Specific in vivo imaging of macrophages in atherosclerosis with a targeted multimodal magnetofluorescent nanoparticle SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Ctr Mol Imaging Rsch, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 339 EP 339 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802235 ER PT J AU Okamoto, Y Shimizu, K Colvin, R Minami, M Kihara, S Funahashi, T Luster, A Libby, P AF Okamoto, Yoshihisa Shimizu, Koichi Colvin, Richard Minami, Manabu Kihara, Shinji Funahashi, Tohru Luster, Andrew Libby, Peter TI Adiponectin, an anti-inflammatory adipocytokine, regulates T lymphocytes recruitment by inhibiting T lymphocytotropic CXC chemokines in LPS-stimulated macrophages: A potential anti-atherogenic function of adiponectin SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Osaka Univ, Grad Sch Med, Osaka, Japan. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 340 EP 340 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802238 ER PT J AU Aikawa, E Nahrendort, M Sosnovik, D Lok, VM Jaffer, FA Aikawa, M Weissleder, R AF Aikawa, Elena Nahrendort, Matthias Sosnovik, David Lok, Vincent M. Jaffer, Farouc A. Aikawa, Masanori Weissleder, Ralph TI Molecular imaging identifies inflammation and precalcification in aortic valve disease SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1799 BP 359 EP 359 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802302 ER PT J AU Stewart, GC Weintraub, J Semigran, MJ Camuso, J Tsang, SW Anello, MS Nguyen, VT Ewis, EF Nohria, A Desai, AS Givertz, MM Stevenson, LW AF Stewart, Garrick C. Weintraub, Joanne Semigran, Marc J. Camuso, Janice Tsang, Sui W. Anello, Mary Susan Nguyen, Viviane T. Ewis, Eldrin F. Nohria, Anju Desai, Akshay S. Givertz, Michael M. Stevenson, Lynne Warner TI Patient misperceptions about the survival benefit of implantable defibrillators for primary prevention of death in heart failure SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 376 EP 376 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802379 ER PT J AU Nieman, K Shapiro, M Ferencik, M Nomura, C Abbara, S Hoffmann, U Jang, IK Brady, T Cury, R AF Nieman, Koen Shapiro, Michael Ferencik, Maros Nomura, Cesar Abbara, Suhny Hoffmann, Udo Jang, Ik-Kyung Brady, Thomas Cury, Ricardo TI Myocardial infarction imaging by early and late-phase 64-slice CT in comparison to MRI SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 384 EP 385 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802413 ER PT J AU Virmani, R Malik, S Burke, A Skorija, K Wong, N Kolodgie, F Narula, J AF Virmani, Renu Malik, Shalsta Burke, Allen Skorija, Krist Wong, Nathan Kolodgie, Frank Narula, Jagat TI Vulnerable plaque pathology for imagers SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 CV Pathol, Gaithersburg, MD USA. Univ Calif Irvine, Irvine, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 385 EP 385 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802416 ER PT J AU Turakhia, M Ali, S Schiller, NB Whooley, MA AF Turakhia, Mintu Ali, Sadia Schiller, Nelson B. Whooley, Mary A. TI Left ventricular mass predicts death and sudden death in patients with CAD regardless of ejection fraction: Data from the heart & soul study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 404 EP 404 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802498 ER PT J AU Mega, JL Becker, JR Sabatine, MS AF Mega, Jessica L. Becker, Jason R. Sabatine, Marc S. TI A 31-year-old woman with fever, rash, facial swelling, and fulminant heart failure SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 407 EP 407 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802508 ER PT J AU Jaffer, FA Nahrendorf, M Vinegoni, C John, MC Aikawa, E Uchibashi, M Finn, AV Ntziachristos, V Libby, P Gold, HK Weissleder, R AF Jaffer, Farouc A. Nahrendorf, Matthias Vinegoni, Claudio John, Michael C. Aikawa, Elena Uchibashi, Mayu Finn, Aloke V. Ntziachristos, Vasilis Libby, Peter Gold, Herman K. Weissleder, Ralph TI In vivo imaging of protease activity in atherosclerosis using a near-infrared fluorescence intravascular catheter SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 414 EP 414 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802538 ER PT J AU Fukuoka, Y Lindgren, T Rankin, SH Carroll, D AF Fukuoka, Yoshimi Lindgren, Teri Rankin, Sally H. Carroll, Diane TI Cluster analysis of elderly cardiac patients based on prehospital symptomatology SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 428 EP 428 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802593 ER PT J AU Trimarchi, S Nienaber, CA Tsai, T Llovet, A Froehlich, J Rampoldi, V Grassi, V Pape, L Oh, J Cooper, JV Gilon, D Fattori, R Issellbacher, EM Eagle, KA AF Trimarchi, Santi Nienaber, Christoph A. Tsai, Thomas Llovet, Alfredo Froehlich, Jim Rampoldi, Vincenzo Grassi, Viviana Pape, Linda Oh, Jae Cooper, Jeanna V. Gilon, Dan Fattori, Rossella Issellbacher, Eric M. Eagle, Kim A. CA Int Registry Acute Aortic D TI In search for optimal treatment of complicated acute type B aortic dissections: Insights from the International Registry of Aortic Dissection (IRAD) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Orsola Marcello Malpighi Hosp, Bologna, Italy. Hadassah Univ Hosp, Tel Aviv, Israel. Mayo Clin, Rochester, MN USA. Univ Massachusetts, Worcester, MA 01605 USA. Policlin San Donato, San Donato Milanese, Italy. Hosp Univ 12 Octubre, Madrid, Spain. Univ Rostock, Rostock, Germany. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 436 EP 437 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802631 ER PT J AU Tsai, TT Nienaber, CA Issellbacher, EM Trimarchi, S Bossone, E Evangelista, A O'Gara, P Suzuki, T Hutchison, S Cooper, JV Meinhardt, G Myrmel, T Eagle, KA Froehlich, J AF Tsai, Thomas T. Nienaber, Christoph A. Issellbacher, Eric M. Trimarchi, Santi Bossone, Eduardo Evangelista, Arturo O'Gara, Patrick Suzuki, Toru Hutchison, Stuart Cooper, Jeanna V. Meinhardt, Gabriel Myrmel, Truls Eagle, Kim A. Froehlich, James TI Acute type A aortic dissection: Does a primary tear in the aortic arch affect management and outcomes? Insights from the International Registry of Acute Aortic Dissection (IRAD) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Tromso Hosp, N-9012 Tromso, Norway. Robert Bosch Krankenhaus, Stuttgart, Germany. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Tokyo, Tokyo, Japan. Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp Gen Univ Vall Hebron, Barcelona, Spain. CNR, Lecce, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Policlin San Donato, San Donato Milanese, Italy. Univ Rostock, Rostock, Germany. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 436 EP 436 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802630 ER PT J AU Tsai, TT Issellbacher, EM Trimarchi, S Bossone, E Pape, L Januzzi, JL Evangelista, A Oh, JK Llovet, A Beckman, J Cooper, JV Froehlich, J Fattori, R Eagle, KA Nienaber, CA AF Tsai, Thomas T. Issellbacher, Eric M. Trimarchi, Santi Bossone, Eduardo Pape, Linda Januzzi, James L. Evangelista, Arturo Oh, Jae K. Llovet, Alfredo Beckman, Joshua Cooper, Jeanna V. Froehlich, James Fattori, Rossella Eagle, Kim A. Nienaber, Christoph A. TI Acute type B aortic dissection: Does aortic arch involvement affect management and outcomes? Insights from the International Registry Acute Aortic Dissection (IRAD) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Rostock, Rostock, Germany. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Hosp S Orsola, Bologna, Italy. Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp Univ 12 Octubre, Madrid, Spain. Hosp Gen Univ Vall Hebron, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts Hosp, Worcester, MA USA. CNR, Lecce, Italy. Policlin San Donato, San Donato Milanese, Italy. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 437 EP 437 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802632 ER PT J AU Morss, A Swanson, J Vermylen, D Bonab, AA Hoffmann, U Cury, R Brady, TJ Fischman, AJ Tawakol, A AF Morss, Alex Swanson, Jeffrey Vermylen, David Bonab, Ali A. Hoffmann, Udo Cury, Ricardo Brady, Thomas J. Fischman, Alan J. Tawakol, Ahmed TI Immune modulation with granulocyte/macrophage colony-stimulating factor enhances PET imaging of inflamed atherosclerotic plaques SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 447 EP 447 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803038 ER PT J AU Hoffmann, U Nagurney, JT Moselewski, F Pena, A Ferencik, M Chae, CU Cury, RC Butler, J Abbara, S Brown, DF Manini, A Nichols, JH Achenbach, S Brady, TJ AF Hoffmann, Udo Nagurney, John T. Moselewski, Fabian Pena, Antonio Ferencik, Maros Chae, Claudia U. Cury, Ricardo C. Butler, Javed Abbara, Suhny Brown, David F. Manini, Alex Nichols, John H. Achenbach, Stephan Brady, Thomas J. TI Coronary multidetector computed tomography in the assessment of patients with acute chest pain SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 449 EP 449 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803045 ER PT J AU Rieber, J Mooyaart, EA Reichardt, B Gupta, R Hoffmann, U AF Rieber, Johannes Mooyaart, Eline A. Reichardt, Benjamin Gupta, Rajiv Hoffmann, Udo TI Comparison of MDCT and the novel flat panel volume CT for the quantification of coronary artery calcification and vessel dimensions SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 449 EP 449 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803046 ER PT J AU Joner, M Finn, AV Kolodgie, FD Burke, AP Ladich, E Gold, HK Virmani, R AF Joner, Michael Finn, Aloke V. Kolodgie, Frank D. Burke, Allen P. Ladich, Elena Gold, Herman K. Virmani, Renu TI Lack of neointimal growth is a predictor of late stent thrombosis SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. CVPath, Gaithersburg, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 453 EP 453 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803062 ER PT J AU Kinlay, S Schwartz, GG Olsson, AG Rifai, N Szarek, M Libby, P Ganz, P AF Kinlay, Scott Schwartz, Gregory G. Olsson, Anders G. Rifai, Nader Szarek, Michael Libby, Peter Ganz, Peter TI Risk of death and beneficial effects of statins in acute coronary syndromes related to inflammatory markers in the MIRACL study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 VA Boston Healthcare Syst, Boston, MA USA. VAMC Denver, Denver, CO USA. Linkoping Univ, Linkoping, Sweden. Childrens Hosp, Boston, MA 02115 USA. Pfizer Inc, New York, NY USA. Brigham & Womens Hosp, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 461 EP 461 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803100 ER PT J AU Volpato, GP Searles, RJ Scherrer-Crosbie, M Bloch, KD Ichinose, F Zapol, WM AF Volpato, Gian Paolo Searles, Robert J. Scherrer-Crosbie, Marielle Bloch, Kenneth D. Ichinose, Fumito Zapol, Warren M. TI Cardiovascular changes after exposure to hydrogen sulfide in a murine model SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 465 EP 465 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803114 ER PT J AU Thibault, H Gomez, L Roesch, O Couture-Lepetit, E Journiaux, J Scherrer-Crosbie, M Ovize, M Derumeaux, G AF Thibault, Helene Gomez, Ludovic Roesch, Odile Couture-Lepetit, Elisabeth Journiaux, Julien Scherrer-Crosbie, Marielle Ovize, Michel Derumeaux, Genevieve TI Effect of age on ischemia-reperfusion consequences in mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 INSERM, E0226, F-69008 Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 483 EP 483 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803197 ER PT J AU Stewart, GC Brooks, K Tsang, SW Semigran, MJ Smith, C James, L Page, D Saniuk, C Fang, JC Mudge, GH Couper, GS Baugham, KL Stevenson, LW AF Stewart, Garrick C. Brooks, Kimberly Tsang, Sui W. Semigran, Marc J. Smith, Colleen James, Linda Page, Deborah Saniuk, Catherine Fang, James C. Mudge, Gilbert H., Jr. Couper, Gregory S. Baugham, Kenneth L. Stevenson, Lynne Warner TI Heart failure patients define threshold for left ventricular assist devices SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 484 EP 484 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803200 ER PT J AU van Kimmenade, RR Januzzi, JL Baggish, A Lainchbury, J Bayes-Genis, A Richards, AM Pinto, YM AF van Kimmenade, Roland R. Januzzi, James L., Jr. Baggish, Aaron Lainchbury, John Bayes-Genis, Antoni Richards, A. M. Pinto, Yigal M. TI NT-proBNP should be used in the definition of the "Cardio-Renal Syndrome" SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Hosp Maastricht, Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Christchurch Hosp, Christchurch, New Zealand. Hosp Santa Creu & Sant Pau, E-08025 Barcelona, Spain. RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 487 EP 487 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803216 ER PT J AU Tawakol, A Vermylen, D Cury, R Hoffmann, U Brady, TJ Fischman, AJ AF Tawakol, Ahmed Vermylen, David Cury, Ricardo Hoffmann, Udo Brady, Thomas J. Fischman, Alan J. TI Metabolic activity within periodontal tissue correlates with carotid plaque inflammation SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 491 EP 491 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803231 ER PT J AU Oikawa, M Yuan, C Underhill, H Chu, B Yu, W Ferguson, MS Hatsukami, TS AF Oikawa, Minako Yuan, Chun Underhill, Hunter Chu, Baocheng Yu, Wei Ferguson, Marina S. Hatsukami, Thomas S. TI Calcification within the advanced human carotid atherosclerotic plaque is associated with intraplaque hemorrhage: A magnetic resonance imaging and histology investigation SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 497 EP 498 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803262 ER PT J AU Joner, M Morimoto, K John, M Finn, AV Listhrop, R Acampado, E Kolodgie, F Virmani, R AF Joner, Michael Morimoto, Katsumi John, Mike Finn, Aloke V. Listhrop, Raelene Acampado, Eduardo Kolodgie, Frank Virmani, Renu TI Site specific targeting of nanoparticle prednisolone prevents in-stent restenosis in a rabbit model of established atheroma SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 CVPATH, Gaithersburg, MD USA. Terumo Cooperat, Inokuchi, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 511 EP 511 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803318 ER PT J AU Scirica, B Stone, PH Murphy, SA Morrow, DA Southard, M Ciaglo, L Harrigan, C Takao, S Jacqueline, B Lew, M Mangan, H Marble, S McCabe, CH Gibson, CM AF Scirica, Benjamin Stone, Peter H. Murphy, Sabina A. Morrow, David A. Southard, Mathew Ciaglo, L. Harrigan, C. Takao, S. Jacqueline, Buros Lew, M. Mangan, H. Marble, Susan McCabe, Carolyn H. Gibson, C. M. CA TIMI Study Grp TIMI Study Grp TI Impaired myocardial perfusion at the end of percutaneous coronary intervention (PCI) is associated with continuous ECG ischemia immediately following PCI which is then associated with myonecrosis hours later. A PROTECT-TIMI 30 substudy SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 512 EP 512 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803325 ER PT J AU Baggish, AL Lloyd-Jones, DM O'Donoghue, M Sakhuja, R Lainchbury, JG Richards, AM Januzzi, JL AF Baggish, Aaron L. Lloyd-Jones, Donald M. O'Donoghue, Michelle Sakhuja, Rahul Lainchbury, John G. Richards, A. Mark Januzzi, James L. TI A validated clinical and biochemical risk score for prediction of one-year mortality in dyspneic emergency department patients: The proBNP investigation of dyspnea in the emergency department (PRIDE) mortality risk score SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. Univ Otego Sch Med, Cardioendocrine Unit, Christchurch, New Zealand. RI Lloyd-Jones, Donald/C-5899-2009 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 529 EP 529 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803397 ER PT J AU Peterson, PN Ho, PM Rumsfeld, JS Lyons, EE Ross, C Smith, S Magid, DJ Permanente, K Masoudi, FA AF Peterson, Pam N. Ho, P. Michael Rumsfeld, John S. Lyons, Ella E. Ross, Colleen Smith, Scott Magid, David J. Permanente, Kaiser Masoudi, Frederick A. TI Exercise capacity on exercise treadmill test predicts future cardiac events SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Denver Hlth Med Ctr, Denver, CO USA. Denver VA Med Ctr, Denver, CO USA. Kaiser Permanente, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 538 EP 538 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803437 ER PT J AU Rieber, J Hacker, M Huber, A Jung, P Erhard, I Koneig, A Poliklinik, M Hoffmann, U Klauss, V Poliklinik, M AF Rieber, Johannes Hacker, Marcus Huber, Armin Jung, Philip Erhard, Isabelle Koneig, Andreas Poliklinik, Medizinische Hoffmann, Udo Klauss, Volker Poliklinik, Medizinische TI Comparison of cardiac magnetic resonance imaging (CMRI) and SPECT for the assessment of flow limiting coronary artery stenoses SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Munich, Dept Nucl Med, Munich, Germany. Univ Munich, Inst Clin Radiol, Munich, Germany. Univ Munich, Med Poliklin, D-8000 Munich, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 538 EP 538 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803438 ER PT J AU Cury, RC Shash, K Nomura, CH Abbara, S Ferencik, M Hoffmann, U T Nagurney, J Schmidt, E Brady, TJ AF Cury, Ricardo C. Shash, Khalid Nomura, Cesar H. Abbara, Suhny Ferencik, Maros Hoffmann, Udo T Nagurney, John Schmidt, Ehud Brady, Thomas J. TI Comprehensive cardiac magnetic resonance imaging protocol in the emergency department: T2W imaging improves diagnostic accuracy for detection of patients with acute coronary syndrome SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Nomura, Cesar/H-1636-2012 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 542 EP 542 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803454 ER PT J AU Ferencik, M Pena, AJ Moselewski, F Nichols, JH Butler, J Jang, IK Brady, TJ Nagurney, JT Hoffmann, U AF Ferencik, Maros Pena, Antonio J. Moselewski, Fabian Nichols, John H. Butler, Javed Jang, Ik-Kyung Brady, Thomas J. Nagurney, John T. Hoffmann, Udo TI Analysis of CT angiographic patterns in patients with vs. without acute coronary syndromes presenting to the emergency department with acute chest pain SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 544 EP 544 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803461 ER PT J AU Feit, F Manoukian, SV Ebrahimi, R Pollack, CV Ohman, EM Attubato, MJ Mehran, R Stone, GW AF Feit, Frederick Manoukian, Steven V. Ebrahimi, Ramin Pollack, Charles V., Jr. Ohman, E. M. Attubato, Michael J. Mehran, Roxana Stone, Gregg W. TI Bivalinudin monotherapy improves 30 day clinical outcomes in diabetics with acute coronary syndrome (ACS). Report from the ACUITY trial SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NYU, Sch Med, New York, NY 19107 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Calif Los Angeles, Los Angeles, CA 10016 USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. Penn Hosp, Philadelphia, PA USA. Duke Univ, Med Ctr, Durham, NC USA. NYU Med Ctr, New York, NY USA. Columbia Univ, Med Ctr, New York, NY USA. Cardiovasc Rsch Fdn, New York, NY 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 551 EP 551 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803485 ER PT J AU Beeri, R Yosefy, C Guerrero, JL Abeidat, S Stroud, R Gilon, D Sullivan, S Chaput, M Vlahakes, GJ Spinale, FG Hajjar, RJ Levine, RA AF Beeri, Ronen Yosefy, Chaim Guerrero, J. Luis Abeidat, Susan Stroud, Robert Gilon, Dan Sullivan, Suzanne Chaput, Miguel Vlahakes, Gus J. Spinale, Francis G. Hajjar, Roger J. Levine, Robert A. TI Early repair of moderate ischemic MR reverses LV remodeling: A functional and molecular study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Hadassah Hebrew Univ Med Ctr, Jerusalem, Israel. Med Univ S Carolina, Charleston, SC 29425 USA. RI Beeri, Ronen/A-4035-2009 OI Beeri, Ronen/0000-0002-8014-0702 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 564 EP 564 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803540 ER PT J AU Hung, JW Chaput, M Guerrero, JL Handschumacher, MD Papakostas, L Levine, RA AF Hung, Judy W. Chaput, Miguel Guerrero, J. L. Handschumacher, Mark D. Papakostas, Lampros Levine, Robert A. TI Persistent reduction of ischemic mitral regurgitation by papillary muscle repositioning: Stabilization of the papillary muscle-ventricular wall complex SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 564 EP 564 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803542 ER PT J AU Poh, KK Raher, MJ Thibault, H Liu, R Derumeaux, G Bloch, KD Picard, MH Scherrer-Crosbie, M AF Poh, Kian Keong Raher, Michael J. Thibault, Helene Liu, Rong Derumeaux, Genevieve Bloch, Kenneth D. Picard, Michael H. Scherrer-Crosbie, Marielle TI Noninvasive quantification of myocardial blood flow in mice: Validation of myocardial contrast echocardiography using microspheres SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 569 EP 569 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803562 ER PT J AU Murphy, SA Gibson, CM Morrow, DA McCabe, CH Van De Werf, F Menown, IB Jiang, F Antman, EM AF Murphy, Sabina A. Gibson, C. Michael Morrow, David A. McCabe, Carolyn H. Van De Werf, Frans Menown, Ian B. Jiang, Frank Antman, Elliott M. TI Does the efficacy of the low-molecular weight heparin enoxaparin over unfractionated heparin balance the safety profile in ST-elevation myocardial infarction? A meta-analysis of 27,000 patients SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 TIMI Study Grp, Boston, MA USA. Sanofi Aventis, Bridgewater, NJ USA. Craigavon Area Hosp, Craigavon, North Ireland. Univ Ziekenhuis Gasthuisberg, Louvain, Belgium. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 599 EP 599 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804039 ER PT J AU Blendea, D Shah, R Mela, T Danik, S Mansour, M Heist, EK Manzke, R Reddy, V Ruskin, J Singh, JP AF Blendea, Dan Shah, Ravi Mela, Theofanie Danik, Stephan Mansour, Moussa Heist, E. K. Manzke, Robert Reddy, Vivek Ruskin, Jeremy Singh, Jagmeet P. TI The best angiographic view for left ventricular lead placement is highly variable between patients: A rotational coronary venography study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 605 EP 605 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804066 ER PT J AU Maddukuri, P Woods, P Joseph, J Aragam, J McIntyre, K Sharma, GVRK AF Maddukuri, Prasad Woods, Patricia Joseph, Jacob Aragam, Jayashri McIntyre, Kevin Sharma, G. V. R. K. TI Non-invasive hemodynamic assessment by Vericor (R) reveals heart failure management by clinical assessment alone is suboptimal in ambulatory patients and leads to increased heart failure hospitalizations SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Boston Med Ctr, Boston, MA USA. CVP Diagnost Inc, Boston, MA USA. Boston Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA 02118 USA. Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA USA. NR 0 TC 2 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 621 EP 621 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804132 ER PT J AU Kinlay, S Schwartz, GG Olsson, AG Rifai, N Szarek, M Waters, D Libby, P Ganz, P AF Kinlay, Scott Schwartz, Gregory G. Olsson, Anders G. Rifai, Nader Szarek, Michael Waters, David Libby, Peter Ganz, Peter TI Risk of stroke after acute coronary syndromes in the MIRACL study related to baseline inflammatory markers SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 VA Boston Healthcare Syst, W Roxbury, MA USA. VAMC Denver, Denver, CO USA. Linkoping Univ, Linkoping, Sweden. Childrens Hosp, Boston, MA 02115 USA. Pfizer Inc, New York, NY USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Brigham & Womens Hosp, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 629 EP 629 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804168 ER PT J AU Sosnovik, DE Nahrendort, M Matsui, T Reynolds, F Dorn, G Rosenzweig, A Weissleder, R Josephson, L AF Sosnovik, David E. Nahrendort, Matthias Matsui, Takashi Reynolds, Fred Dorn, Gerald, III Rosenzweig, Anthony Weissleder, Ralph Josephson, Lee TI Sensitivity of molecular MRI for low levels of cardiomyocyte apoptosis in an in-vivo model of dilated cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 637 EP 637 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804203 ER PT J AU Moukarbel, GV Jneid, HM Awaida, JPS Gonczarek, KM Keck, SA Haggan, CD Pomerantsev, EV Palacios, IF Semigran, MJ AF Moukarbel, George V. Jneid, Hani M. Awaida, Jean-Pierre S. Gonczarek, Kathleen M. Keck, Sally A. Haggan, Coral D. Pomerantsev, Eugene V. Palacios, Igor F. Semigran, Marc J. TI Percutaneous revascularization of transplant coronary disease carries a high restenosis rate that is reduced by drug-eluting stents SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 641 EP 641 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804223 ER PT J AU John, M Finn, AV Wessely, R Kastrati, A Joner, M Uchihashi, M Crimins, J Kolodgie, F Listhrop, R Gold, HK Schomig, A Virmani, R AF John, Mike Finn, Aloke V. Wessely, Rainer Kastrati, Adnan Joner, Michael Uchihashi, Mayu Crimins, Johanna Kolodgie, Frank Listhrop, Raelene Gold, Herman K. Schomig, Albert Virmani, Renu TI Comparison of overlapping non-polymer versus polymer-based DES: Finding a better balance between neointimal suppression and arterial healing SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 CVPath, Gaithersburg, MD USA. Deutsch Herzzentrum Munich, Munich, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 643 EP 644 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804233 ER PT J AU Bonaca, MP Morrow, DA Sabatine, MS Ray, KK Rifai, N Cannon, CP AF Bonaca, Marc P. Morrow, David A. Sabatine, Marc S. Ray, Kausik K. Rifai, Nader Cannon, Christopher P. TI Elevated levels of placental growth factor (PIGF) and long term risk in patients with acute coronary syndrome in PROVE IT-TIMI 22 SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Childrens Hosp & Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 649 EP 649 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804256 ER PT J AU Donahoe, SM Stewart, GC McCabe, CH Murphy, SA Shui, A Gibson, CM Cannon, CP Antman, EM AF Donahoe, Sean M. Stewart, Garrick C. McCabe, Carolyn H. Murphy, Sabina A. Shui, Amy Gibson, C. M. Cannon, Christopher P. Antman, Elliott M. CA TIMI Study Grp TI The impact of diabetes on mortality in acute coronary syndromes: An analysis of 62,035 patients from the TIMI study group SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 649 EP 649 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804258 ER PT J AU Gupta, R Moreiras, J Lago, R Jneid, H Awaida, JP Maree, A Rosenfield, K Inglessis, I Pomerantsev, E Palacios, I AF Gupta, Rakesh Moreiras, Javier Lago, Rodrigo Jneid, Hani Awaida, Jean-Pierre Maree, Andrew Rosenfield, Kenneth Inglessis, Ignacio Pomerantsev, Eugene Palacios, Igor TI Immediate outcomes and complications of percutaneous aortic valvuloplasty: Inoue anterograde transseptal versus conventional retrograde approach SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 656 EP 656 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804289 ER PT J AU Collard, CD Sherman, SK Fox, AK Vaughn, WK Bernig, T Chanock, SJ Takahashi, K Ezekowitz, AB Jarolim, P Body, SC AF Collard, Charles D. Sherman, Stanton K. Fox, Amanda K. Vaughn, William K. Bernig, Toralf Chanock, Stephen J. Takahashi, Kazue Ezekowitz, Alan B. Jarolim, Petr Body, Simon C. TI The MBL2 "LYQA secretor" haplotype is an independent predictor of postoperative myocardial infarction (MI) in Caucasians undergoing coronary artery bypass graft (CABG) surgery SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Biostat & Epidemiol, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, Houston, TX 77030 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 658 EP 658 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804298 ER PT J AU Lewis, GD Lachmann, J Camuso, JM Shin, J Systrom, DM Bloch, KD Semigran, MJ AF Lewis, Gregory D. Lachmann, Justine Camuso, Janice M. Shin, Jordan Systrom, David M. Bloch, Kenneth D. Semigran, Marc J. TI Acute administration of sildenafil improves peak VO2 proportionate to pulmonary vasodilation in patients with heart failure SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 669 EP 669 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804344 ER PT J AU Goehler, A Zietemann, V Siebert, U Anker, SD AF Goehler, Alexander Zietemann, Vera Siebert, Uwe Anker, Stefan D. TI Association between weight change and incidence of congestive heart failure in the framingham heart offspring study - Death as a competing event SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth, Hall In Tirol, Tyrol, Austria. Charit, Dept Cardiol, Div Appl Cachexia Res, Berlin, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 671 EP 671 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804351 ER PT J AU Reddy, VY Neuzil, P Taborsky, M Skoda, J Albers, B Roger, G Mouton, S AF Reddy, Vivek Y. Neuzil, Petr Taborsky, Milos Skoda, J. Albers, Bert Roger, Guido Mouton, Suzanne TI Hybrid ablation and preventive pacing therapy to control persistent ATRIAL FIBRILLATION: THE HAPPI-AF TRIAL SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Na Homolce Hosp, Prague, Czech Republic. Vitatron BV, Arnhem, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 690 EP 691 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804437 ER PT J AU Gibson, CM Murphy, SA McCabe, CH Morrow, DA Antman, EM Braunwald, E AF Gibson, C. Michael Murphy, Sabina A. McCabe, Carolyn H. Morrow, David A. Antman, Elliott M. Braunwald, Eugene TI Association of treatment with non-steroidal anti-inflammatory agents (NSAIDS) on study entry with 30 day adverse outcomes among ST elevation MI (STEMI) patients treated with a fibrinolytic agent. An EXTRACT-TIMI 25 analysis SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 TIMI Study Grp, Boston, MA USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 697 EP 698 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804465 ER PT J AU Morrow, DA Antman, EM McCabe, CH Qin, J Jiang, F Braunwald, E AF Morrow, David A. Antman, Elliott M. McCabe, Carolyn H. Qin, Jie Jiang, Frank Braunwald, Eugene CA TIMI Study Grp TI Effect of enoxaparin vs unfractionated heparin in diabetic patients with ST-elevation MI in the ExTRACT-TIMI 25 trial SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Sanofi Aventis, Clin Dev, Bridgewater, NJ 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 700 EP 700 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804475 ER PT J AU Sabafine, MS Morrow, DA Mohanavelu, S Murphy, SA McCabe, CH Antman, EM Braunwald, E AF Sabafine, Marc S. Morrow, David A. Mohanavelu, Sahshkumar Murphy, Sabina A. McCabe, Carolyn H. Antman, Elliott M. Braunwald, Eugene CA TIMI Study Grp TI Efficacy and safety of enoxaparin vs. UFH in patients with ST-Elevation myocardial infarction also treated or not treated with clopidogrel: Analysis from ExTRACT-TIMI 25 SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 700 EP 700 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804476 ER PT J AU Thiagalingam, A D'Avila, A McPherson, C Malchano, Z Ruskin, J Reddy, V AF Thiagalingam, Aravinda D'Avila, Andre McPherson, Christina Malchano, Zach Ruskin, Jeremy Reddy, Vivek TI Impedance and temperature monitoring improve the safety of irrigated tip radiofrequency ablation SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 705 EP 705 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804497 ER PT J AU Gibson, CM Haim, M Aroesty, JM Ciaglo, L Shui, A Southard, M Harrigan, C Takao, S Marble, SJ Kirtane, AJ Pinto, DS Zimetbaum, PJ Sabatine, MS Cannon, CP Josephson, ME AF Gibson, C. Michael Haim, Moti Aroesty, Julian M. Ciaglo, Lauren Shui, Amy Southard, Matthew Harrigan, Caitlin Takao, Shaun Marble, Susan J. Kirtane, Ajay J. Pinto, Duane S. Zimetbaum, Peter J. Sabatine, Marc S. Cannon, Christopher P. Josephson, Mark E. TI Association of ventricular fibrillation and ventricular tachycardia (VT/VF) with impaired TIMI myocardial perfusion grades (TMPG) even in the presence of normal TIMI grade 3 flow SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RI Haim, Moti/K-7381-2014 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 706 EP 706 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804502 ER PT J AU Sabatine, MS Morrow, DA O'Donoghue, M Jablonski, KA Rice, MM Solomon, SD Rosenberg, YD Domanski, MJ Hsia, J AF Sabatine, Marc S. Morrow, David A. O'Donoghue, Michelle Jablonski, Kathleen A. Rice, Madeline M. Solomon, Scott D. Rosenberg, Yves D. Domanski, Michael J. Hsia, Judith TI Lipoprotein-associated phospholipase A(2) (Lp-PLa2) is an independent predictor of adverse cardiovascular outcomes in patients with stable coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. NHLBI, Bethesda, MD 20892 USA. RI Solomon, Scott/I-5789-2013 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 713 EP 713 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804533 ER PT J AU Poh, KK Levine, RA Chaput, M Guerrero, JL Flaherty, M Kang, YJ Morris, EL Solis, J Klas, B Hung, J AF Poh, Kian Keong Levine, Robert A. Chaput, Miguel Guerrero, Jose Luis Flaherty, Mary Kang, Yue-Jian Morris, Eleanor L. Solis, Jorge Klas, Berthold Hung, Judy TI Assessing aortic valve area in aortic stenosis by continuity equation: A novel approach using real-time three dimensional echocardiography SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tom Tec Corp, Erie, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 716 EP 716 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804544 ER PT J AU Baggish, AL Richards, AM van Kimmenade, RR Bayes-Genis, A Lainchbury, J Pinto, Y Januzzi, JL AF Baggish, Aaron L. Richards, A. Mark van Kimmenade, Roland R. Bayes-Genis, Antoni Lainchbury, John Pinto, Yigal Januzzi, James L., Jr. TI Amino-terminal pro-brain natriuretic peptide testing is superior to New York Heart Association classification for prediction of one-year mortality in patients with acute heart failure: Results from the International Collaborative of NT-proBNP Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Christchurch Hosp, Christchurch, New Zealand. Acad Hosp Maastricht, Maastricht, Netherlands. Hosp Santa Creu & Sant Pau, Barcelona, Spain. RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 720 EP 720 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804560 ER PT J AU Januzzi, JL Peacock, WF Jesse, RL Maisel, AS Newell, JB Baggish, AL Sakhuja, R O'Donoghue, M Chen, AA van Kimmenade, RR Lewandrowski, KB Wu, AB AF Januzzi, James L., Jr. Peacock, W. Frank Jesse, Robert L. Maisel, Alan S. Newell, John B. Baggish, Aaron L. Sakhuja, Rahul O'Donoghue, Michelle Chen, Annabel A. van Kimmenade, Roland R. Lewandrowski, Kent B. Wu, Alan B. TI The value of soluble ST2 measurement for the diagnostic and prognostic evaluation of patients with acute dyspnea SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Acad Hosp Maastricht, Maastricht, Netherlands. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Kimmenade, R.R.J./L-4432-2015 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 721 EP 721 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804566 ER PT J AU Tawakoi, A Cury, R Hoffmann, U Vermylen, D Swanson, J Bedri, S Moloo, J Morss, A Fischman, AJ Brady, TJ AF Tawakoi, Ahmed Cury, Ricardo Hoffmann, Udo Vermylen, David Swanson, Jeffrey Bedri, Shahinaz Moloo, Jamaluddin Morss, Alexander Fischman, Alan J. Brady, Thomas J. TI Combined PET-CT assessment of carotid plaque inflammation: A human histopathological study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 726 EP 726 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804587 ER PT J AU Raffel, OC Merchant, FM Tearney, GJ Bouma, BE Jang, IK AF Raffel, O. C. Merchant, Faisal M. Tearney, Guillermo J. Bouma, Brett E. Jang, Ik-Kyung TI Positive coronary artery remodeling is associated with underlying vulnerable plaque characterized by intravascular optical coherence tomography SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 730 EP 730 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804606 ER PT J AU Raffel, OC Tearney, GJ Gauthier, DAD Halpern, EF Bouma, BE Jang, IK AF Raffel, O. C. Tearney, Guillermo J. Gauthier, Denise A. DeJoseph Halpern, Elkan F. Bouma, Brett E. Jang, Ik-Kyung TI Plaque fibrous cap macrophage density and the peripheral white cell count predict the presence of thin-cap fibroatheroma: an intravascular optical coherence tomography study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 730 EP 730 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804604 ER PT J AU Raffel, OC Bouma, BE Tearney, GJ Jang, IK AF Raffel, O. C. Bouma, Brett E. Tearney, Guillermo J. Jang, Ik-Kyung TI Comparison of coronary plaque characteristics between diabetic and non-diabetic subjects: An in-vivo optical coherence tomography study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 730 EP 731 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804607 ER PT J AU Singh, M Rihal, C Lennon, R Spertus, J Rumsfeld, J Holmes, D AF Singh, Mandeep Rihal, Charanjit Lennon, Ryan Spertus, John Rumsfeld, John Holmes, David TI Bedside estimation of risk from percutaneous coronary interventions: The new Mayo Clinic risk scores? SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Mayo Clin, Rochester, MN USA. Mid Amer Heart Inst, Kansas City, MO USA. Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 733 EP 733 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804617 ER PT J AU Scirica, BM Morrow, DA Giugliano, RP Wiviott, SD Sabatine, MS Shui, A McCabe, CH Antman, EM Braunwald, E AF Scirica, Benjamin M. Morrow, David A. Giugliano, Robert P. Wiviott, Stephen D. Sabatine, Marc S. Shui, Amy McCabe, Carolyn H. Antman, Elliott M. Braunwald, Eugene TI Enoxaparin reduces recurrent MI and death in patients with STEMI undergoing fibrinolysis who achieve early ST resolution: The ExTRACT-TIMI 25 ECG study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 743 EP 743 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804662 ER PT J AU Reddy, V Neuzil, P Themistoclakis, S Bonso, A Rossillo, A Raviele, A Saliba, W Schwiekert, R Ernst, S Kuck, KH Ruskin, J Natale, A AF Reddy, Vivek Neuzil, Petr Themistoclakis, Sakis Bonso, Aldo Rossillo, Antonio Raviele, Antonio Saliba, Walid Schwiekert, Robert Ernst, Sabine Kuck, Karl-Heinz Ruskin, Jeremy Natale, Andrea TI Long-term single-procedure clinical results with an endoscopic balloon ablation catheter for pulmonary vein isolation in patients with atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Homolka Hosp, Prague, Czech Republic. Umberto Hosp, Venice, Italy. Cleveland Clin Fdn, Cleveland, OH 44195 USA. St Georg Hosp, Hamburg, Germany. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 747 EP 748 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804682 ER PT J AU Heist, EK Chevalier, J Holmvang, G Singh, JP Ellinor, PT Milan, DJ D'Avila, A Mela, T Ruskin, JN Mansour, M AF Heist, E. Kevin Chevalier, Jianping Holmvang, Godtfred Singh, Jagmeet P. Ellinor, Patrick T. Milan, David J. D'Avila, Andre Mela, Theofanie Ruskin, Jeremy N. Mansour, Moussa TI Factors affecting error in integration of electroanatomic mapping with computed tomographic and magnetic resonance imaging during catheter ablation of atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 748 EP 748 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804683 ER PT J AU Saam, T Hatsukami, TS Underhill, H Chu, B Takaya, N Cai, J Yuan, C AF Saam, Tobias Hatsukami, Thomas S. Underhill, Hunter Chu, Baocheng Takaya, Norhide Cai, Jianming Yuan, Chun TI Prevalence of AHA type VI carotid lesions identified by MRI across different categories of stenosis measured by duplex ultrasound SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Munich, Dept Clin Radiol, Munich, Germany. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Juntendo Univ, Sch Med, Dept Cardiol, Tokyo 113, Japan. Peoples Liberat Army Gen Hosp, Dept Radiol, Beijing, Peoples R China. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 776 EP 776 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805115 ER PT J AU Zoghbi, GJ Goyal, MK Hage, FG Brott, BC Misra, VK Myers, PR Hillegass, WB AF Zoghbi, Gilbert J. Goyal, Munish K. Hage, Fadi G. Brott, Brigitta C. Misra, Vijay K. Myers, Paul R. Hillegass, William B. TI Prophylactic sodium nitroprusside administration in saphenous vein graft intervention reduces post-procedural cardiac marker elevation SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. St Thomas Med Ctr, Nashville, TN 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 786 EP 786 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805160 ER PT J AU Dada, M O'Rourke, RA Teo, KK Hartigan, PM Knudtson, M Kostuk, W Maron, DJ Casperson, P Weintraub, WS Boden, WE AF Dada, Marcin O'Rourke, Robert A. Teo, Koon K. Hartigan, Pamela M. Knudtson, Merril Kostuk, William Maron, David J. Casperson, Paul Weintraub, William S. Boden, William E. TI Long-term adherence to the ACC/AHA class I post-discharge medications and recommendations using optimal medical therapy in 2,287 patients with established coronary heart disease: Interim data from the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Hartford Hosp, Hartford, CT 06115 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. McMaster Univ, Hlth Sci Ctr, Hamilton, ON, Canada. Vet Affairs Cooperat Studies Program Coordinating, VA Connecticut Healthcare Syst, West Haven, CT USA. Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. Hlth Sci Ctr, London, ON, Canada. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Christiana Care Hlth Syst, Newark, DE USA. Ctr Outcomes Rech, Newark, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 798 EP 798 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805212 ER PT J AU Ruff, CT Wiviott, SD Amman, EM Shui, A McCabe, CH Morrow, D AF Ruff, Christian T. Wiviott, Stephen D. Amman, Elliott M. Shui, Amy McCabe, Carolyn H. Morrow, David TI Effect of risk an the benefit of enoxaparin versus unfractionated heparin in patients with ST-elevation myocardial infarction in the ExTRACT-TIMI 25 trial SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 814 EP 814 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805284 ER PT J AU Glickman, SW Mulgund, J Lytle, BL Rumsfeld, JS Roe, MT Gibler, WB Ohman, EM Fintel, D Schulman, KA Peterson, ED AF Glickman, Seth W. Mulgund, Jyotsna Lytle, Barbara L. Rumsfeld, John S. Roe, Matthew T. Gibler, W. Brian Ohman, E. Magnus Fintel, Dan Schulman, Kevin A. Peterson, Eric D. TI The impact of pay for performance (P4P) on quality of care in acute coronary syndromes: Initial external evaluation of the center for medicare and medicaid services P4P pilot SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Duke Clin Res Inst, Durham, NC USA. Denver VA Med Ctr, Denver, CO USA. Univ Cincinnati, Sch Med, Cincinnati, OH 45221 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 835 EP 835 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805371 ER PT J AU Kathiresan, S Massaro, JM Cury, RC Manders, ES Cupples, LA Hoffmann, U O'Donnell, CJ AF Kathiresan, Sekar Massaro, Joseph M. Cury, Ricardo C. Manders, Emily S. Cupples, L. Adrienne Hoffmann, Udo O'Donnell, Christopher J. TI Long-term exposure to traditional atherosclerotic risk factors and presence of aortic valve calcification SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 840 EP 840 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805386 ER PT J AU Rumsfeld, JS Masoudi, FA Jones, PG Havranek, E Peterson, ED Krumholz, HM Spertus, JA AF Rumsfeld, John S. Masoudi, Frederick A. Jones, Philip G. Havranek, Edward Peterson, Eric D. Krumholz, Harlan M. Spertus, John A. TI Predictors of 1-year quality of life after acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Denver VA Med Ctr, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. St Lukes Hosp, Mid Amer Heart Inst, UMKC, Kansas City, MO 64111 USA. Duke Univ, Med Ctr, Durham, NC USA. Yale Univ, Med Ctr, New Haven, CT 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 842 EP 842 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805392 ER PT J AU Shapira, OM Korach, A Benjamin, E Lovett, A Silverstein, T Agnihotri, AK Torchiana, DF Shemin, RJ Normand, SL AF Shapira, Oz M. Korach, Amit Benjamin, Emelia Lovett, Ann Silverstein, Treacy Agnihotri, Arvind K. Torchiana, David F. Shemin, Richard J. Normand, Sharon-Lise TI The impact of race and insurance status on utilization rates and outcomes after coronary artery bypass grafting surgery in the commonwealth of Massachusetts SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Boston Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 860 EP 860 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805473 ER PT J AU ODonoghue, E Kenney, P Oestreicher, E Anwaruddin, S Baggish, AL Tung, R Krauser, DG Chen, A Sakhuja, R Januzzi, JL AF ODonoghue, Michelle Kenney, Patrick Oestreicher, Eveline Anwaruddin, Saif Baggish, Aaron L. Tung, Roderick Krauser, Daniel G. Chen, Annabel Sakhuja, Rahul Januzzi, James L. TI The diagnostic and prognostic value of NT-proBNP in diabetic patients with dyspnea: A ProBNP investigation of dyspnea in the emergency department (PRIDE) sub-study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 872 EP 872 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805518 ER PT J AU Kathiresan, S Larson, MG Massaro, JM Rong, J Keaney, JF Kiel, DP Vasan, RS O'Donnell, CJ Benjamin, EJ AF Kathiresan, Sekar Larson, Martin G. Massaro, Joseph M. Rong, Jian Keaney, John F., Jr. Kiel, Douglas P. Vasan, Ramachandran S. O'Donnell, Christopher J. Benjamin, Emelia J. TI Serum osteoprotegerin levels are related to vascular risk factors and vascular calcification in the community: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Hebrew Rehabil Cntr Aged Rsch, Boston, MA USA. Training Inst, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 874 EP 874 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805526 ER PT J AU Deo, R Fyr, CLW Fried, LF Newman, AB Harris, TB Angleman, S Green, C Kritchevsky, SB Chertow, G Cummings, SR Shlipak, MG AF Deo, Rajat Fyr, Christina L. Wassel Fried, Linda F. Newman, Anne B. Harris, Tamara B. Angleman, Sara Green, Christie Kritchevsky, Stephen B. Chertow, Glenn Cummings, Steven R. Shlipak, Michael G. TI Cystatin C and cardiovascular events in the elderly: The health, aging, and body composition (Health ABC) study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN 38163 USA. Wake Forest Sch Med, Winston Salem, NC USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 875 EP 875 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805533 ER PT J AU Pou, KM Massaro, JM Hoffman, U Vasan, RS Maurovich-Horvat, P Larson, MG Keaney, JF Meigs, JB Lipinska, I Murabito, JM O'Donnell, CJ Benjamin, EJ Fox, CS AF Pou, Karla M. Massaro, Joseph M. Hoffman, Udo Vasan, Ramachandran S. Maurovich-Horvat, Pal Larson, Martin G. Keaney, John F., Jr. Meigs, James B. Lipinska, Izabella Murabito, Joanne M. O'Donnell, Christopher J. Benjamin, Emelia J. Fox, Caroline S. TI Visceral and subcutaneous adipose tissue volumes are related to markers of inflammation and oxidative stress: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Semmelweis Univ, H-1085 Budapest, Hungary. Boston Univ, Sch Med, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 877 EP 877 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805539 ER PT J AU Fox, CS Massaro, JM Hoffmann, U Pou, KM Maurovich-Horvat, P Vasan, RS Murabito, JM D'Agostino, RB O'Donnell, CJ AF Fox, Caroline S. Massaro, Joseph M. Hoffmann, Udo Pou, Karla M. Maurovich-Horvat, Pal Vasan, Ramachandran S. Murabito, Joanne M. D'Agostino, Ralph B., Sr. O'Donnell, Christopher J. TI The joint impact of visceral adipose tissue and body mass index on metabolic risk factors for cardiovascular disease: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Endocrinol, Framingham, MA USA. Boston Univ, Dept Cardiol, Boston, MA 02215 USA. Boston Univ, Dept Gen Med, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 885 EP 885 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805577 ER PT J AU Nishida, T Searles, RJ Shigematsu, M Janssens, S Bloch, KD Ichinose, F AF Nishida, Takefumi Searles, Robert J. Shigematsu, Misako Janssens, Stefan Bloch, Kenneth D. Ichinose, Fumito TI Cardiac-specific NOS3 overexpression rescues myocardial and neuronal function after cardiopulmonary resuscitation in NOS3-deficient mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Leuven, Louvain, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 1203 EP 1203 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805750 ER PT J AU Sandri, M Lin, JD Handschin, C Yang, WL Arany, ZP Lecker, SH Goldberg, AL Spiegelman, BM AF Sandri, Marco Lin, Jiandie Handschin, Christoph Yang, Wenli Arany, Zoltan P. Lecker, Stewart H. Goldberg, Alfred L. Spiegelman, Bruce M. TI PGC-1 alpha a protects skeletal muscle from atrophy by suppressing Fox03 action and atrophy-specific gene transcription SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE denervation; fasting; muscle fiber; energy metabolism; mitochondria ID UBIQUITIN-PROTEASOME PATHWAY; SIGNALING PATHWAYS; DENERVATION ATROPHY; COACTIVATOR PGC-1; FOOD-DEPRIVATION; EXPRESSION; EXERCISE; DEGRADATION; GROWTH; RATS AB Maintaining muscle size and fiber composition requires contractile activity. Increased activity stimulates expression of the transcriptional coactivator PGC-1 alpha (peroxisome proliferator-activated receptor gamma coactivator 1 alpha), which promotes fiber-type switching from glycolytic toward more oxidative fibers. In response to disuse or denervation, but also in fasting and many systemic diseases, muscles undergo marked atrophy through a common set of transcriptional changes. FoxO family transcription factors play a critical role in this loss of cell protein, and when activated, FoxO3 causes expression of the atrophy-related ubiquitin ligases atrogin-1 and MuRF-1 and profound loss of muscle mass. To understand how exercise might retard muscle atrophy, we investigated the possible interplay between PGC-1 alpha and the FoxO family in regulation of muscle size. Rodent muscles showed a large decrease in PGC-1 alpha mRNA during atrophy induced by denervation as well as by cancer cachexia, diabetes, and renal failure. Furthermore, in transgenic mice overexpressing PGC-1 alpha, denervation and fasting caused a much smaller decrease in muscle fiber diameter and a smaller induction of atrogin-1 and MuRF-1 than in control mice. Increased expression of PGC-1a also increased mRNA for several genes involved in energy metabolism whose expression decreases during atrophy. Transfection of PGC-1 alpha into adult fibers reduced the capacity of FoxO3 to cause fiber atrophy and to bind to and transcribe from the atrogin-1 promoter. Thus, the high levels of PGC-1 alpha in dark and exercising muscles can explain their resistance to atrophy, and the rapid fall in PGC-1 alpha during atrophy should enhance the FoxO-dependent loss of muscle mass. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA 02115 USA. Venetian Inst Mol Med, I-35129 Padua, Italy. Dulbecco Telethon Inst, I-35129 Padua, Italy. Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. RP Goldberg, AL (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, C1-411,240 Longwood Ave, Boston, MA 02115 USA. EM alfred-goldberg@hms.harvard.edu; bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [2R56 DK 054477, P30 DK040561, P30 DK040561-11, R01 DK 62307-01, R56 DK054477]; Telethon [TCP04009] NR 52 TC 420 Z9 428 U1 2 U2 29 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 OCT 31 PY 2006 VL 103 IS 44 BP 16260 EP 16265 DI 10.1073/pnas.0607795103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103IS UT WOS:000241879500037 PM 17053067 ER PT J AU Zhao, JJ Cheng, HL Jia, SD Wang, L Gjoerup, OV Mikami, A Roberts, TM AF Zhao, Jean J. Cheng, Hailing Jia, Shidong Wang, Li Gjoerup, Ole V. Mikami, Aki Roberts, Thomas M. TI The p110 alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adipocyte differentiation; cancer therapy; conditional knockout; PIK3CA ID 3-KINASE CATALYTIC SUBUNIT; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; LUNG-CANCER; B-CELL; EMBRYONIC LETHALITY; EGFR MUTATIONS; P110-DELTA; MICE; KINASE AB Growth factor signaling is mediated through Class IA phosphatidylinositol 3-kinases (PI3Ks). Among this class of enzymes, only p110 alpha, encoded by the PIK3CA gene, has been found to be mutant in human cancers. To determine the specific functions of p110 alpha, we generated mice carrying a conditionally targeted allele of the PIK3CA gene. Here, we report that PIK3CA-knockout mouse embryonic fibroblasts are deficient in cellular signaling in response to various growth factors, unable to differentiate into adipocytes, and resistant to oncogenic transformation induced by a variety of oncogenic receptor tyrosine kinases, indicating a fundamental role for p110 alpha in these biological processes. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1058B, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu FU NCI NIH HHS [P01 CA 50661, 5P50 CA 090381-05, CA 30002, P01 CA 089021, P01 CA050661, P01 CA089021, P50 CA090381, R01 CA030002, R37 CA030002] NR 28 TC 118 Z9 120 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 31 PY 2006 VL 103 IS 44 BP 16296 EP 16300 DI 10.1073/pnas.0607899103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103IS UT WOS:000241879500043 PM 17060635 ER PT J AU Chen, ZB Stockton, J Mathis, D Benoist, C AF Chen, Zhibin Stockton, John Mathis, Diane Benoist, Christophe TI Modeling CTLA4-linked autoimmunity with RNA interference in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmune diabetes; imprinting; lentiviral transgene; RNAi; variegation ID LENTIVIRAL VECTORS; T-CELLS; CTLA-4-DEFICIENT MICE; STEM-CELLS; CTLA-4; GENE; EXPRESSION; SUSCEPTIBILITY; POLYMORPHISMS; PROMOTER AB The CTLA4 gene is important for T lymphocyte-mediated immunoregulation and has been associated with several autoimmune diseases, in particular, type 1 diabetes. To model the impact of natural genetic variants of CTLA4, we constructed RNA interference (RNAi) "knockdown" mice through lentiviral transgenesis. Variegation of expression was observed in founders but proved surmountable because it reflected parental imprinting, with derepression by transmission from male lentigenics. Unlike the indiscriminate multiorgan autoimmune phenotype of the corresponding knockout mice, Ctla4 knockdown animals had a disease primarily focused on the pancreas, with rapid progression to diabetes. As with the human disease, the knockdown phenotype was tempered by genetic-modifier loci. RNAi should be more pertinent than gene ablation in modeling disease pathogenesis linked to a gene-dosage variation. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Mathis, D (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIAID NIH HHS [P01 AI 56299-04, P01 AI056299] NR 29 TC 37 Z9 39 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 31 PY 2006 VL 103 IS 44 BP 16400 EP 16405 DI 10.1073/pnas.0607854103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103IS UT WOS:000241879500061 PM 17060611 ER PT J AU Lin, T Xiang, ZM Cui, LB Stallcup, W Reeves, SA AF Lin, Tong Xiang, Zhongmin Cui, Libin Stallcup, William Reeves, Steven A. TI New mouse oligodendrocyte precursor (mOP) cells for studies on oligodendrocyte maturation and function SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE oligodendrocyte; precursor; mouse; culture; myelin ID CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; RAT-BRAIN; GLIAL PROGENITORS; ARCHIVAL GLIOMAS; GROWTH-FACTORS; DIFFERENTIATION; OLIGOSPHERES; ASTROCYTES; CULTURE AB Oligodendrocyte precursor (OP) cells give rise to mature oligodendrocytes (OL), which are necessary for myelination of axons during CNS development and following damage to the myelin sheath that occurs in demyelinating diseases. To facilitate studies designed to understand OP maturation and OL function, we have developed OP cells that can be grown continuously, expanded, and differentiated into mature OLs. Cultures of late passage mOP cells grown in proliferation medium are highly pure early stage oligodendrocyte precursors where > 90% assume a characteristic bipolar morphology. Immunocytochemical analysis using antibodies that recognize progressive stages of OP maturation (A2B5, NG2, GD3 and O4) confirmed that mOP cells have a stable early stage OP cell phenotype. In addition, mOP cells can be induced to differentiate into mature forms of oligodendrocytes in vitro and in vivo, as characterized morphologically by the presence of multiple processes with secondary and tertiary branches, and by immunostaining and quantitative real-time PCR for the mature oligodendrocyte markers MBP, MAG, PLP, and MOBP. Finally, differentiation of mOP cells was accompanied by up-regulation of mRNA encoding Olig2 but not Olig1, which is consistent with previous findings showing that Olig2 is necessary for specification of oligodendrocytes. These new mOP cells should significantly benefit in vitro and in vivo studies on OP maturation and function. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, CNS Singaling Lab, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Burnham Inst, Dev Neurobiol Program, La Jolla, CA 92037 USA. RP Reeves, SA (reprint author), Massachusetts Gen Hosp, CNS Singaling Lab, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM sreeves@partners.org FU NINDS NIH HHS [R01NS35996] NR 41 TC 23 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 30 PY 2006 VL 157 IS 2 BP 187 EP 194 DI 10.1016/j.jneumeth.2006.04.014 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 101PU UT WOS:000241753600001 PM 16720048 ER PT J AU Qin, GS Hsu, YS Zhou, XH AF Qin, Gengsheng Hsu, Yu-Sheng Zhou, Xiao-Hua TI New confidence intervals for the difference between two sensitivities at a fixed level of specificity SO STATISTICS IN MEDICINE LA English DT Article DE specificity; sensitivity; diagnostic tests; bootstrap; confidence intervals ID BINOMIAL PROPORTIONS AB For two continuous-scale diagnostic tests, it is of interest to compare their sensitivities at a predetermined level of specificity. In this paper, we propose three new intervals for the difference between two sensitivities at a fixed level of specificity. These intervals are easy to compute. We also conduct simulation studies to compare the relative performance of the new intervals with the existing normal-approximation-based interval proposed by Wieand et al. Our simulation results show that the newly proposed intervals perform better than the existing normal-approximation-based interval in terms of coverage accuracy and interval length. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. NW HSR&D Ctr Excellence, VA Puget Sound Healthcare Syst, Biostat Unit, Seattle, WA 98101 USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, 1705 NE Pacific St,Box 357232, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU NIBIB NIH HHS [R01EB005829] NR 9 TC 10 Z9 10 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 30 PY 2006 VL 25 IS 20 BP 3487 EP 3502 DI 10.1002/sim.2459 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 093UT UT WOS:000241196500007 PM 16345124 ER PT J AU Bhattacharya, A Chandrasekar, B Rahman, MM Banu, J Kang, JX Fernandes, G AF Bhattacharya, Arunabh Chandrasekar, Bysani Rahman, Md Mizanur Banu, Jameela Kang, Jing X. Fernandes, Gabriel TI Inhibition of inflammatory response in transgenic fat-1 mice on a calorie-restricted diet SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE fat-1; n-3 fatty acids; calorie-restriction; cytokines; NF-kappa B; AP-1; inflammation; splenocytes ID N-3 FATTY-ACIDS; NF-KAPPA-B; FISH-OIL; RHEUMATOID-ARTHRITIS; OXIDATIVE STRESS; IMMUNE-SYSTEM; TNF-ALPHA; LIPOPOLYSACCHARIDE; AGE; EXPRESSION AB Both n - 3 fatty acids (n-3 FA) and calorie-restriction (CR) exert anti-inflammatory effects in animal models of autoimmunity and inflammation. In the present study we investigated the synergistic anti-inflammatory effects of n-3 FA and CR on LPS-mediated inflammatory responses using fat-1 transgenic mice that generate n-3 FA endogenously. Wild-type (WT) and fat-1 mice were maintained on ad libitum (AL) or CR (40% less than AL) diet for 5 mo; splenocytes were cultured in vitro with/without LPS. Our results show: (i) no difference in body weights between WT and fat-1 mice on AL or CR diets, (ii) lower n-6/n-3 FA ratio in splenocytes from fat-1 mice on both AL and CR diets, (iii) significant reduction in NF-kappa B (p65/p5O) and AP-1 (c-Fos/c-Jun) DNA-binding activities in splenocytes from fat-1/CR mice following LPS treatment, and (iv) significant reduction in kappa B- and AP-1-responsive IL-6 and TNF-alpha secretion following LPS treatment in splenocytes from fat-1/CR mice. The inhibition of LPS-mediated effects was more pronounced in fat-1/CR mice when compared to fat-1/AL or WT/CR mice. These data show that transgenic expression of fat-1 results in decreased pro-inflammatory n-6 FA, and demonstrate for the first time that splenocytes from fat-1 mice on CR diet exhibit reduced pro-inflammatory response when challenged with LPS. These results suggest that n-3 lipids with moderate CR may confer protection in autoimmune and inflammatory diseases. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol & Rheumatol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fernandes, G (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol & Rheumatol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM fernandes@uthscsa.edu FU NIA NIH HHS [AG023648, AG027562] NR 42 TC 36 Z9 38 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 27 PY 2006 VL 349 IS 3 BP 925 EP 930 DI 10.1016/j.bbrc.2006.08.093 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 089UW UT WOS:000240907800008 PM 16962071 ER PT J AU Hiltunen, M Lu, A Thomas, AV Romano, DM Kim, M Jones, PB Xie, Z Kounnas, MZ Wagner, SL Berezovska, O Hyman, BT Tesco, G Bertram, L Tanzi, RE AF Hiltunen, Mikko Lu, Alice Thomas, Anne V. Romano, Donna M. Kim, Minji Jones, Phill B. Xie, Zhongcong Kounnas, Maria Z. Wagner, Steven L. Berezovska, Oksana Hyman, Bradley T. Tesco, Giuseppina Bertram, Lars Tanzi, Rudolph E. TI Ubiquilin 1 modulates amyloid precursor protein trafficking and A beta secretion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; CELL-SURFACE; PRESENILIN ENDOPROTEOLYSIS; MISSENSE MUTATIONS; GENE; ONSET; GAMMA; IDENTIFICATION; DEGRADATION; GENERATION AB Ubiquilin 1 (UBQLN1) is a ubiquitin-like protein, which has been shown to play a central role in regulating the proteasomal degradation of various proteins, including the presenilins. We recently reported that DNA variants in UBQLN1 increase the risk for Alzheimer disease, by influencing expression of this gene in brain. Here we present the first assessment of the effects of UBQLN1 on the metabolism of the amyloid precursor protein (APP). For this purpose, we employed RNA interference to down-regulate UBQLN1 in a variety of neuronal and non-neuronal cell lines. We demonstrate that down-regulation of UBQLN1 accelerates the maturation and intracellular trafficking of APP, while not interfering with alpha-, beta-, or gamma-secretase levels or activity. UBQLN1 knockdown increased the ratio of APP mature/immature, increased levels of full-length APP on the cell surface, and enhanced the secretion of sAPP (alpha- and beta-forms). Moreover, UBQLN1 knockdown increased levels of secreted A beta 40 and A beta 42. Finally, employing a fluorescence resonance energy transfer-based assay, we show that UBQLN1 and APP come into close proximity in intact cells, independently of the presence of the presenilins. Collectively, our findings suggest that UBQLN1 may normally serve as a cytoplasmic "gatekeeper" that may control APP trafficking from intracellular compartments to the cell surface. These findings suggest that changes in UBQLN1 steady-state levels affect APP trafficking and processing, thereby influencing the generation of A beta. C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Torrey Pines Therapeut Inc, La Jolla, CA 92037 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114 16th St C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015; OI Bertram, Lars/0000-0002-0108-124X; Jones, Phillip/0000-0003-0525-6323 FU NIA NIH HHS [5P01 AG 015379-08, 1R01 AG 023667-01] NR 41 TC 57 Z9 58 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 OCT 27 PY 2006 VL 281 IS 43 BP 32240 EP 32253 DI 10.1074/jbc.M603106200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 096ZB UT WOS:000241414500021 PM 16945923 ER PT J AU Dean, T Khatri, A Potetinova, Z Willick, GE Gardella, TJ AF Dean, Thomas Khatri, Ashok Potetinova, Zhanna Willick, Gordon E. Gardella, Thomas J. TI Role of amino acid side chains in region 17-31 of parathyroid hormone (PTH) in binding to the PTH receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID (PTH)/PTH-RELATED PROTEIN-RECEPTOR; JUXTAMEMBRANE REGION; PTH/PTHRP RECEPTOR; LIGAND INTERACTION; CROSS-LINKING; ANALOGS; PEPTIDE; DOMAIN; DOCKING; SITE AB The principal receptor-binding domain (Ser(17)-Val(31)) of parathyroid hormone (PTH) is predicted to form an amphiphilic alpha-helix and to interact primarily with the N-terminal extracellular domain (N domain) of the PTH receptor (PTHR). We explored these hypotheses by introducing a variety of substitutions in region 17-31 of PTH-(1-31) and assessing, via competition assays, their effects on binding to the wild-type PTHR and to PTHR-delNt, which lacks most of the N domain. Substitutions at Arg(20) reduced affinity for the intact PTHR by 200-fold or more, but altered affinity for PTHR-delNt by 4-fold or less. Similar effects were observed for Glu substitutions at Trp(23), Leu(24), and Leu(28), which together form the hydrophobic face of the predicted amphiphilic alpha-helix. Glu substitutions at Arg(25), Lys(26), and Lys(27) (which forms the hydrophilic face of the helix) caused 4-10-fold reductions in affinity for both receptors. Thus, the side chains of Arg(20), together with those composing the hydrophobic face of the ligand's putative amphiphilic alpha-helix, contribute strongly to PTHR-binding affinity by interacting specifically with the N domain of the receptor. The side chains projecting from the opposite helical face contribute weakly to binding affinity by different mechanisms, possibly involving interactions with the extracellular loop/transmembrane domain region of the receptor. The data help define the roles that side chains in the binding domain of PTH play in the PTH-PTHR interaction process and provide new clues for understanding the overall topology of the bimolecular complex. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman Bldg,Rm 503C,50 Blossom St, Boston, MA 02114 USA. EM gardella@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 11794] NR 39 TC 19 Z9 19 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 OCT 27 PY 2006 VL 281 IS 43 BP 32485 EP 32495 DI 10.1074/JBC.M606179200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 096ZB UT WOS:000241414500046 PM 16923805 ER PT J AU Ahmed, AR Spigelman, Z Cavacini, LA Posner, MR AF Ahmed, A. Razzaque Spigelman, Zachary Cavacini, Lisa A. Posner, Marshall R. TI Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; MUCOCUTANEOUS BLISTERING DISEASES; IMMUNOGLOBULIN THERAPY; AUTOIMMUNE-DISEASES; ADJUVANT THERAPY; REMISSION; TRANSPLANTATION; AUTOANTIBODIES; RECALCITRANT; OPTIONS AB BACKGROUND: Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous blistering disease. Conventional therapy consists of high-dose corticosteroids, immunosuppressive agents, and intravenous immune globulin. METHODS: We studied patients with refractory pemphigus vulgaris involving 30% or more of their body-surface area, three or more mucosal sites, or both who had inadequate responses to conventional therapy and intravenous immune globulin. We treated the patients with two cycles of rituximab (375 mg per square meter of body-surface area) once weekly for 3 weeks and intravenous immune globulin (2 g per kilogram of body weight) in the fourth week. This induction therapy was followed by a monthly infusion of rituximab and intravenous immune globulin for 4 consecutive months. Titers of serum antibodies against keratinocytes and numbers of peripheral-blood B cells were monitored. RESULTS: Of 11 patients, 9 had rapid resolution of lesions and a clinical remission lasting 22 to 37 months (mean, 31.1). All immunosuppressive therapy, including prednisone, could be discontinued before ending rituximab treatment in all patients. Two patients were treated with rituximab only during recurrences and had sustained remissions. Titers of IgG4 antikeratinocyte antibodies correlated with disease activity. Peripheral-blood B cells became undetectable shortly after initiating rituximab therapy but subsequently returned to normal values. Side effects that have been associated with rituximab were not observed, nor were infections. CONCLUSIONS: The combination of rituximab and intravenous immune globulin is effective in patients with refractory pemphigus vulgaris. C1 New England Baptist Hosp, Ctr Blistering Dis, Boston, MA 02120 USA. New England Baptist Hosp, Parker Hill Oncol & Hematol, Boston, MA 02120 USA. New England Baptist Hosp, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Waltham Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Human Monoclonal Antibody Lab, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), New England Baptist Hosp, Ctr Blistering Dis, 70 Parker Hill Ave,Suite 208, Boston, MA 02120 USA. NR 39 TC 232 Z9 240 U1 1 U2 6 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 OCT 26 PY 2006 VL 355 IS 17 BP 1772 EP 1779 DI 10.1056/NEJMoa062930 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 098HV UT WOS:000241512500005 PM 17065638 ER PT J AU Chung, RT Misdraji, J Sahani, DV Goldfinger, SE AF Chung, Raymond T. Misdraji, Joseph Sahani, Dushyant V. Goldfinger, Stephen E. TI A man with diabetes, hypogonadism, cirrhosis, arthralgias, and fatigue - Hereditary hemochromatosis due to a homozygous C282Y mutation in the HFE gene, with hepatic cirrhosis, diabetes, and hypogonadism. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IRON OVERLOAD; LIVER; EXPRESSION; MANAGEMENT; HEPCIDIN; DISEASE C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 26 PY 2006 VL 355 IS 17 BP 1812 EP 1819 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 098HV UT WOS:000241512500013 PM 17065644 ER PT J AU Chandan, VS Faquin, WC Wilbur, DC Khurana, KK AF Chandan, Vishal S. Faquin, William C. Wilbur, David C. Khurana, Kamal K. TI The role of immunolocalization of CD57 and GLUT-1 in cell blocks in fine-needle aspiration diagnosis of papillary thyroid carcinoma SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE cytology; papillary carcinoma; fine-needle aspiration; thyroid; immunohistochemistry; CD57; GLUT-1 ID ADENOID CYSTIC CARCINOMA; NATURAL-KILLER CELLS; FOLLICULAR VARIANT; LEU-7 ANTIGEN; KIT CD117; EXPRESSION; NEOPLASMS; NODULES; LESIONS; MARKER AB BACKGROUND. CD57 (Leu7), a marker for natural killer lymphocytes, and glucose transporter-1 (GLUT-1), a facilitative cell surface glucose transport protein, are expressed in a wide spectrum of epithelial malignancies. The usefulness of CD57 and GLUT-1 immunostaining was evaluated as an adjunct to assist in the diagnosis of papillary carcinoma in fine-needle aspirations (FNAs) of the thyroid. METHODS. inummohistochemical staining for CD57 and GLUT-1 was performed on paraffin-embedded cell blocks of 50 thyroid FNA cases with the following cytologic diagnoses: 1) papillary carcinoma (15 cases); 2) atypical cytology, cannot exclude papillary carcinoma (14 cases); and 3) benign thyroid (21 cases). RESULTS. Fourteen of 15 cases with an unequivocal diagnosis of papillary carcinoma were positive for CD57 and I case was negative for CD57. Tissue follow-up confirmed papillary carcinoma in all 15 cases. Of the 14 cases with a diagnosis of atypical cytology, cannot exclude papillary carcinoma, 6 cases were positive for CD57 and subsequent excision confirmed papillary carcinoma in all 6 cases. The remaining 8 cases negative for CD57 included surgically confirmed goiter (5 cases), adenoma (2 cases), and papillary carcinoma (1 case). The follicular cells in all 21 cases with a cytologic diagnosis of benign thyroid were negative for CD57. Histologic follow-up of these cases confirmed the benign cytologic diagnoses. GLUT-1 was negative in all cases. The sensitivity and specificity of CD57 was 91% and 100%, respectively. CONCLUSIONS. CD57 immunostaining is a useful adjunct for the diagnosis of papillary thyroid carcinoma in cell block material. Although negative staining for CD57 does not completely exclude papillary carcinoma, positive staining aids in the accurate diagnosis of malignancy in cytomorphologically equivocal cases. GLUT-1 did not prove to be a useful marker in distinguishing papillary carcinomas. C1 SUNY Upstate Med Univ, Dept Pathol, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Khurana, KK (reprint author), SUNY Upstate Med Univ, Dept Pathol, 750 E Adams St, Syracuse, NY 13210 USA. EM khuranak@upstate.edu RI Chandan, Vishal/K-8860-2015 NR 42 TC 17 Z9 20 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 BP 331 EP 336 DI 10.1002/cncr.22172 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 098EL UT WOS:000241503700010 PM 16944537 ER PT J AU Knoepp, S Kuebler, D Wilbur, D AF Knoepp, Stewart Kuebler, Diane Wilbur, David TI Equivocal results of hybrid capture II high-risk HPV DNA: A cytologic/histologic review of 191 cases SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 SU S BP 342 EP 343 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 098MC UT WOS:000241523700012 ER PT J AU Rego, M Wilbur, D AF Rego, Mary Wilbur, David TI FocalPoint "no further review" population: False negative performance as determined by "'high risk" rescreening SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 SU S BP 366 EP 366 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 098MC UT WOS:000241523700058 ER PT J AU Hamilton, L Green, L AF Hamilton, Lesley Green, Linda TI Low serum alpha fetoprotein in hepatocellular carcinoma in the US: A continued need for liver fine needle aspiration SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 SU S BP 403 EP 403 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 098MC UT WOS:000241523700130 ER PT J AU Balco, M Mezzadra, H Kincaid, E Tambouret, R Altiok, S AF Balco, Mike Mezzadra, Heather Kincaid, Erik Tambouret, Rosemary Altiok, Soner TI Determining the primary site of metastatic adenocarcinoma in liver by SELDI-TOF mass spectrometry SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 SU S BP 407 EP 407 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 098MC UT WOS:000241523700139 ER PT J AU Belsley, N Johnson, M Tambouret, R AF Belsley, Nicole Johnson, Matthew Tambouret, Rosemary TI Trends in fine needle aspiration and core biopsy of the kidney: The impact of radiofrequency ablation for treatment of kidney tumors SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 SU S BP 409 EP 409 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 098MC UT WOS:000241523700143 ER PT J AU Velasco, V Galan, K Gattuso, P Green, L AF Velasco, Veronica Galan, Kristin Gattuso, Paolo Green, Linda TI A review of 68 metastatic malignancies of inguinal lymph nodes diagnosed by superficial FNA: Where, oh, where may the primary tumor be? SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. ME Debakey Vet Affairs Med Ctr, Houston, TX USA. Rush Univ, Med Ctr, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 SU S BP 415 EP 415 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 098MC UT WOS:000241523700154 ER PT J AU Liu, JH Zingmond, DS McGory, ML SooHoo, NF Ettner, SL Brook, RH Ko, CY AF Liu, Jerome H. Zingmond, David S. McGory, Marcia L. SooHoo, Nelson F. Ettner, Susan L. Brook, Robert H. Ko, Clifford Y. TI Disparities in the utilization of high-volume hospitals for complex surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TRANSLUMINAL CORONARY ANGIOPLASTY; UNITED-STATES; OPERATIVE MORTALITY; SURGICAL MORTALITY; UNINSURED ADULTS; OUTCOMES; ASSOCIATION; HEALTH; RISK; RACE AB Context Referral to high-volume hospitals has been recommended for operations with a demonstrated volume-outcome relationship. The characteristics of patients who receive care at low-volume hospitals may be different from those of patients who receive care at high-volume hospitals. These differences may limit their ability to access or receive care at a high-volume hospital. Objective To identify patient characteristics associated with the use of high-volume hospitals, using California's Office of Statewide Health Planning and Development patient discharge database. Design, Setting, and Participants Retrospective study of Californians receiving the following inpatient operations from 2000 through 2004: elective abdominal aortic aneurysm repair, coronary artery bypass grafting, carotid endarterectomy, esophageal cancer resection, hip fracture repair, lung cancer resection, cardiac valve replacement, coronary angioplasty, pancreatic cancer resection, and total knee replacement. Main Outcome Measures Patient race/ethnicity and insurance status in high-volume ( highest 20% of patients by mean annual volume) and in low-volume ( lowest 20%) hospitals. Results A total of 719 608 patients received 1 of the 10 operations. Overall, non-whites, Medicaid patients, and uninsured patients were less likely to receive care at high-volume hospitals and more likely to receive care at low-volume hospitals when controlling for other patient-level characteristics. Blacks were significantly ( P <. 05) less likely than whites to receive care at high-volume hospitals for 6 of the 10 operations ( relative risk [RR] range, 0.40-0.72), while Asians and Hispanics were significantly less likely to receive care at high-volume hospitals for 5 ( RR range, 0.60-0.91) and 9 ( RR range, 0.46-0.88), respectively. Medicaid patients were significantly less likely than Medicare patients to receive care at high-volume hospitals for 7 of the operations ( RR range, 0.22-0.66), while uninsured patients were less likely to be treated at high-volume hospitals for 9 ( RR range, 0.20-0.81). Conclusions There are substantial disparities in the characteristics of patients receiving care at high-volume hospitals. The interest in selective referral to high-volume hospitals should include explicit efforts to identify the patient and system factors required to reduce current inequities regarding their use. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ctr Surg Outcomes & Qual, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Ctr Surg Outcomes & Qual, 10833 Le Conte Ave,72-215 CHS,Box 956904, Los Angeles, CA 90095 USA. EM cko@mednet.ucla.edu FU NIA NIH HHS [1K08AG023024] NR 33 TC 238 Z9 238 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 25 PY 2006 VL 296 IS 16 BP 1973 EP 1980 DI 10.1001/jama.296.16.1973 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 098BL UT WOS:000241495300019 PM 17062860 ER PT J AU Duda, JE AF Duda, J. E. TI Striatal pathology in the Lewy body disorders SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT International Symposium on Dementia in Parkinson's Disease CY OCT 24-27, 2004 CL Salzburg, AUSTRIA C1 Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 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 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 25 PY 2006 VL 248 IS 1-2 MA 199 BP 323 EP 323 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 109JX UT WOS:000242305200244 ER PT J AU Barbour, JD Hecht, FM Little, SJ Markowitz, M Daar, ES Kelleher, AD Routy, JP Campbell, TB Rosenberg, ES Segal, MR Weidler, J Grant, RM AF Barbour, Jason D. Hecht, Frederick M. Little, Susan J. Markowitz, Martin Daar, Eric S. Kelleher, Anthony D. Routy, Jean-Pierre Campbell, Thomas B. Rosenberg, Eric S. Segal, Mark R. Weidler, Jodi Grant, Robert M. TI Greater CD4 T-cell gains after one year of antiretroviral therapy are associated with lower HIV-1 pol replication capacity SO AIDS LA English DT Article ID PHENOTYPIC DRUG SUSCEPTIBILITY; INFECTED PATIENTS; VIREMIA; ADULTS; SUPPRESSION; TYPE-1 AB We sought to determine whether pretreatment low pol replication capacity (po/RC) is associated with CD4 T-cell count gains during antiretroviral therapy (ART). Patients were recruited at north American and Australian sites. Viral po/RC was measured before starting ART in all subjects. We examined 243 individuals for a median 260 days after initiating ART. Low baseline po/RC was associated with greater CD4 T-cell gains independent of virological responses. C1 Univ Calif San Francisco, Dept Med, Posit Hlth Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Bioinformat & Mol Biostat, San Francisco, CA 94143 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Aaron Diamond AIDS Res Ctr, New York, NY USA. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA USA. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Monogram Biosci Inc, San Francisco, CA USA. Gladstone Inst Virol & Immunol, San Francisco, CA USA. RP Barbour, JD (reprint author), Univ Calif San Francisco, Dept Med, Posit Hlth Program, San Francisco, CA 94143 USA. FU NCRR NIH HHS [M01-RR00102, M01-RR00425]; NIAID NIH HHS [K01 AI066917, 5 U01 AI043638, AI36214, AI41531, AI41534, AI43271, AI43638, AI47033, AI52403, AI54907, AI55356] NR 13 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 24 PY 2006 VL 20 IS 16 BP 2123 EP 2125 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 104ZW UT WOS:000242000100018 PM 17053362 ER PT J AU Tofler, GH Muller, JE AF Tofler, Geoffrey H. Muller, James E. TI Triggering of acute cardiovascular disease and potential preventive strategies SO CIRCULATION LA English DT Review DE myocardial infarction; plaque; risk factors; stress; thrombosis; circadian rhythm ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; SUDDEN CARDIAC DEATH; CASE-CROSSOVER ANALYSIS; EUROPEAN FOOTBALL CHAMPIONSHIP; PUBLIC-ACCESS DEFIBRILLATION; EPIDEMIOLOGY PROGRAM SHEEP; HEAVY PHYSICAL EXERTION; CIRCADIAN VARIATION; AIR-POLLUTION C1 Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tofler, GH (reprint author), Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. EM gtofler@nsccahs.health.nsw.gov.au NR 105 TC 135 Z9 139 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 24 PY 2006 VL 114 IS 17 BP 1863 EP 1872 DI 10.1161/CIRCULATIONAHA.105.596189 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 098AB UT WOS:000241490900014 PM 17060396 ER PT J AU Chou, S Ning, MM Buonanno, F AF Chou, Sherry Ning, Mingming Buonanno, Ferdinando TI Focal intraparenchymal tension pneumocephalus SO NEUROLOGY LA English DT Article C1 Massachusetts Gen Hosp, Neurosci Intens Care Unit, Boston, MA 02114 USA. RP Chou, S (reprint author), Massachusetts Gen Hosp, Neurosci Intens Care Unit, Blake 12,15 Fruit St, Boston, MA 02114 USA. EM schou1@partners.org RI Chou, Sherry/G-5779-2015 NR 2 TC 4 Z9 4 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 OCT 24 PY 2006 VL 67 IS 8 BP 1485 EP 1485 DI 10.1212/01.wnl.0000229141.21182.6c PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 098BI UT WOS:000241494800035 PM 17060581 ER PT J AU Artavanis-Tsakonas, K Love, JC Ploegh, HL Vyas, JM AF Artavanis-Tsakonas, Katerina Love, J. Christopher Ploegh, Hidde L. Vyas, Jatin M. TI Recruitment of CD63 to Cryptococcus neoformans phagosomes requires acidification SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dendritic cells; live cell imaging; lysosome; phagocytosis; yeast ID IMMATURE DENDRITIC CELLS; HEMATOPOIETIC STEM-CELLS; CLASS-II COMPLEXES; MYCOBACTERIUM-TUBERCULOSIS; TETRASPAN MICRODOMAINS; ANTIGEN PRESENTATION; HLA-DR; MATURATION; MACROPHAGES; PROTEIN AB The subcellular localization of the cluster of differentiation 63 (CD63) tetraspanin and its interaction with the class II MHC antigen presentation pathway were examined in the context of phagocytosis by live cell imaging, by using monomeric red fluorescent protein-tagged mouse CD63 expressed in primary bone marrow-derived cell cultures. Upon phagocytosis of Cryptococcus neoformans and polystyrene beads, CD63 was recruited selectively to C neoformans-containing phagosomes in a MyD88-independent acidification-dependent manner. Bead-containing phagosomes, within a C neoformans-containing cell, acidified to a lesser extent and failed to recruit CD63 to a level detectable by microscopy. CD63 recruitment to yeast phagosomes occurred independently of class 11 MHC and LAMP-1. These observations indicate that the composition of distinct phagosomal compartments within the same cell is determined by phagosomal cargo and may affect the outcome of antigen processing and presentation. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. CBR, Biomed Res Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. RP Ploegh, HL (reprint author), Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. EM ploegh@wi.mit.edu; jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU NCI NIH HHS [1F32CA105862-01, F32 CA105862]; NIAID NIH HHS [R01 AI034893, 5K08AI57999, 5R01AI034893-13, K08 AI057999] NR 45 TC 35 Z9 36 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2006 VL 103 IS 43 BP 15945 EP 15950 DI 10.1073/pnas.0607528103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099BW UT WOS:000241568500040 PM 17043215 ER PT J AU Elmaleh, DR Fischman, AJ Tawakol, A Zhu, A Shoup, TM Hoffmann, U Brownell, AL Zamecnik, PC AF Elmaleh, D. R. Fischman, A. J. Tawakol, A. Zhu, A. Shoup, T. M. Hoffmann, U. Brownell, A. -L Zamecnik, P. C. TI Detection of inflamed atherosclerotic lesions with diadenosine-5 ',5 '''-P-1,P-4-tetraphosphate (AP(4)A) and positron-emission tomography SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atherosclerosis; vascular damage; plaque imaging ID SMOOTH-MUSCLE CELLS; CAROTID ATHEROSCLEROSIS; PLAQUE; ULTRASOUND; INFLAMMATION; ANTIBODIES; RECEPTORS; INSIGHTS; DISEASE; AGENTS AB Diadenosine-5', 5"'-P-1, P-4-tetraphosphate (Ap(4)A) and its analog P-2,P-3-monochloromethylene diadenosine-5',5"'-P-1,P-4-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P-2,P-3-[F-18]monofluoromethylene diadenosine-5',5'"-P-1,P-4-tetraphosphate ([F-18]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [F-18]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [F-18]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [F-18]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [F-18]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [F-18]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02114 USA. RP Elmaleh, DR (reprint author), Massachusetts Gen Hosp, Dept Med, MC 1494005,149 13th St, Charlestown, MA 02129 USA. EM delmaleh@partners.org FU NIAID NIH HHS [5 R01 AI060872-02, R01 AI060872] NR 34 TC 23 Z9 24 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 OCT 24 PY 2006 VL 103 IS 43 BP 15992 EP 15996 DI 10.1073/pnas.0607246103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099BW UT WOS:000241568500048 PM 17038498 ER PT J AU Chauhan, D Hideshima, T Anderson, KC AF Chauhan, D. Hideshima, T. Anderson, K. C. TI A novel proteasome inhibitor NPI-0052 as an anticancer therapy SO BRITISH JOURNAL OF CANCER LA English DT Review DE protein degradation; proteasomes; multiple myeloma; novel therapy; apoptosis; drug resistance ID MULTICATALYTIC PROTEINASE COMPLEX; MULTIPLE-MYELOMA CELLS; SALINOSPORAMIDE-A; IN-VIVO; BORTEZOMIB; UBIQUITIN; PS-341; SPECIFICITY; TARGET; MECHANISMS AB Proteasome inhibitor Bortezomib/Velcade has emerged as an effective anticancer therapy for the treatment of relapsed and/or refractory multiple myeloma ( MM), but prolonged treatment can be associated with toxicity and development of drug resistance. In this review, we discuss the recent discovery of a novel proteasome inhibitor, NPI-0052, that is distinct from Bortezomib in its chemical structure, mechanisms of action, and effects on proteasomal activities; most importantly, it overcomes resistance to conventional and Bortezomib therapies. In vivo studies using human MM xenografts shows that NPI-0052 is well tolerated, prolongs survival, and reduces tumour recurrence. These preclinical studies provided the basis for Phase-I clinical trial of NPI-0052 in relapsed/refractory MM patients. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA 100707, CA 78373, P50 CA100707, R01 CA 50947] NR 36 TC 101 Z9 107 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 23 PY 2006 VL 95 IS 8 BP 961 EP 965 DI 10.1038/sj.bjc.6603406 PG 5 WC Oncology SC Oncology GA 096NP UT WOS:000241384400003 PM 17047643 ER PT J AU Ma, YH Li, JX Chiu, I Wang, YW Sloane, JA Lu, JN Kosaras, B Sidman, RL Volpe, JJ Vartanian, T AF Ma, Yinghua Li, Jianxue Chiu, Isaac Wang, Yawen Sloane, Jacob A. Lu, Jining Kosaras, Bela Sidman, Richard L. Volpe, Joseph J. Vartanian, Timothy TI Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; INNATE IMMUNITY; DROSOPHILA; CELLS; ACTIVATION; EVOLUTION; INFECTION; SURVIVAL; PATHWAY AB Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons. Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner. Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR-NF-kappa B signaling pathway. These findings reveal novel functions for TLR8 in the mammalian nervous system that are distinct from the classical role of TLRs in immunity. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Neurodegenerat & Repair, Boston, MA 02115 USA. Harvard Univ, Sch Med, Grad Program Immunol, Ctr Blood Res, Boston, MA 02115 USA. Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Vartanian, T (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. EM tvartani@bidmc.harvard.edu FU NINDS NIH HHS [P01 NS038475, P01NS038475] NR 21 TC 152 Z9 157 U1 3 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 23 PY 2006 VL 175 IS 2 BP 209 EP 215 DI 10.1083/jcb.200606016 PG 7 WC Cell Biology SC Cell Biology GA 099EO UT WOS:000241575500003 PM 17060494 ER PT J AU White, CJ Iyer, SS Hopkins, LN Katzen, BT Jaff, MR AF White, Christopher J. Iyer, Sriram S. Hopkins, L. Nelson Katzen, Barry T. Jaff, Michael R. CA BEACH Trial Investigators TI Two-year follow-up after carotid stent placement in the high surgical risk BEACH trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 18th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 22-27, 2006 CL Washington, DC C1 Ochsner Clin Fdn, New Orleans, LA USA. Lenox Hill Hosp, New York, NY 10021 USA. SUNY Buffalo, Buffalo, NY USA. Massachusetts Gen Hosp, Baptist Hosp, Boston, MA USA. RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 22 PY 2006 VL 98 IS 8A SU S BP 10M EP 11M PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097JG UT WOS:000241442800023 ER PT J AU Cheruvu, PK Finn, A Virmani, R Goldstein, J Stone, GW Gardner, C Caplan, J Muller, JE AF Cheruvu, Pavan K. Finn, Aloke Virmani, Renu Goldstein, James Stone, Gregg W. Gardner, Craig Caplan, Jay Muller, James E. TI Focality and composition of thin cap fibroatheroma, suspected precursors of coronary plaque rupture SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 18th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 22-27, 2006 CL Washington, DC C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA USA. CVPath Inst Inc, Gaithersburg, MD USA. William Beaumont Hosp, Detroit, MI 10027 USA. Columbia Univ, Ctr Med, New York, NY USA. InfraRedx Inc, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 22 PY 2006 VL 98 IS 8A SU S BP 36M EP 36M PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097JG UT WOS:000241442800077 ER PT J AU Palacios, IF Condado, JA Brandi, S Rodriguez, V Silva, G Rogers, JH Low, RI AF Palacios, Igor F. Condado, Jose A. Brandi, Sergio Rodriguez, Victor Silva, Gaston Rogers, Jason H. Low, Reginald I. TI First-in-man: Percutaneous septal sinus shortening (The PS3 system) for functional mitral regurgitation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 18th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 22-27, 2006 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Med Caracas, Caracas, Venezuela. Hosp Univ Caracas, Caracas, Venezuela. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 22 PY 2006 VL 98 IS 8A SU S BP 49M EP 49M PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097JG UT WOS:000241442800105 ER PT J AU Jaff, MR Rocha-Singlr, K Kelley, L Sandager-Hadley, G AF Jaff, Michael R. Rocha-Singlr, Krishna Kelley, Lynne Sandager-Hadley, Gail TI Duplex ultrasonography is the optimal method to determine renal artery in-stent restenosis: Results of the RENAISSANCE trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 18th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 22-27, 2006 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Prairie Heart & Vasc Inst, Springfield, IL USA. Boston Sci Corp, Natick, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 22 PY 2006 VL 98 IS 8A SU S BP 107M EP 107M PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097JG UT WOS:000241442800254 ER PT J AU Palloshi, A Hayase, M Montorfano, M Carlino, M Airoldi, F Sangiorgi, M Godino, C Colombo, A AF Palloshi, Altin Hayase, Motoyo Montorfano, Matteo Carlino, Mauro Airoldi, Flavio Sangiorgi, Massimo Godino, Cosmo Colombo, Antonio TI First in man study of a percutaneous deployed myocardial implant (VPASS(TM) myocardial implant) for the treatment of refractory angina: First in man experience SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 18th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 22-27, 2006 CL Washington, DC C1 Hosp San Raffaele, I-20132 Milan, Italy. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 22 PY 2006 VL 98 IS 8A SU S BP 192M EP 192M PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097JG UT WOS:000241442800485 ER PT J AU Mori, S Endo, M Asakura, H AF Mori, Shinichiro Endo, Masahiro Asakura, Hiroshi TI Improvement in banding artefacts in four-dimensional computed tomography for radiotherapy planning SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CORRELATED IMAGE-RECONSTRUCTION; MULTISLICE SPIRAL CT; RESPIRATORY MOTION; PERFORMANCE EVALUATION; CLINICAL POTENTIALS; PORCINE MODEL; SCANNER; HEART; COMPENSATION; RESOLUTION AB Respiratory-gated CT (RGCT) and four-dimensional CT (4DCT) scan techniques cover consecutive segments of the respiratory cycle. However, motion artefacts may occur in fast respiratory phases such as mid-inhalation and -exhalation. CT imaging involves the use of a number of x-ray tube positions for each couch position. We investigated the fundamental nature of motion artefacts using a constant-velocity moving phantom in motion in the CT plane or perpendicular to the CT plane, and in pigs to simulate a human model. Artefacts and movement distance were evaluated in a moving phantom and artificially ventilated pigs with a 256-multi-detector row CT (256MDCT). The phantom moved in the CT plane or perpendicular to the CT plane with a constant velocity. Backprojection used variable initial backprojection angles (IBAs). The phantom length for motion perpendicular to the CT plane was independent of IBA but was represented by phantom diameter plus the distance of movement per gantry rotation. In contrast, that for the motion in the CT plane was dependent on IBA, as represented by phantom diameter plus the distance of movement per rotation for IBA perpendicular to the phantom movement direction, and phantom diameter plus half the distance of movement per gantry rotation for other IBAs. Results for volumetric CT images with different IBAs showed the presence of banding artefacts. Similar findings were seen in artificially ventilated pigs. Motion artefacts are unavoidable in both conventional CT and 256MDCT. Banding artefacts will be improved if the same IBAs at each couch position are accounted for during image reconstruction. This improvement will be beneficial in respiratory gated and 4D radiation therapies. C1 Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan. Natl Inst Radiol Sci, Dept Planning & Management, Inage Ku, Chiba 2638555, Japan. Accelerator Engn Corp, Inage Ku, Chiba 2630043, Japan. RP Mori, S (reprint author), Massachusetts Gen Hosp, 100 Blossom St,COX 3, Boston, MA 02114 USA. EM smori1@partners.org OI Mori, Shinichiro/0000-0002-0412-4399 NR 34 TC 2 Z9 2 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 21 PY 2006 VL 51 IS 20 BP 5231 EP 5244 DI 10.1088/0031-9155/51/20/010 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 092GE UT WOS:000241084200010 PM 17019035 ER PT J AU Fu, JR Lin, GS Wu, ZW Ceng, B Wu, YX Liang, G Qin, GJ Li, JN Chiu, I Liu, DX AF Fu, Jinrong Lin, Guosheng Wu, Zhiwei Ceng, Bin Wu, Yanxia Liang, Gong Qin, Gangjian Li, Jinan Chiu, Isaac Liu, Dongxu TI Anti-apoptotic role for C1 inhibitor in ischemia/reperfusion-induced myocardial cell injury SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE complement; C1 inhibitor; apoptosis; myocytes; infarction; ischemia; reperfusion; hypoxia; reoxygenation ID ISCHEMIA-REPERFUSION INJURY; ESTERASE INHIBITOR; C1-ESTERASE INHIBITOR; PROTEASE INHIBITORS; ARTERY OCCLUSION; ENDOTOXIN-SHOCK; BRAIN ISCHEMIA; INFARCTION; THERAPY; LIPOPOLYSACCHARIDE AB Complement activation augments myocardial cell injury and apoptosis during ischernialtreperfusion (I/R), whereas complement system inhibition with C I inhibitor (C1INH), a serine protease inhibitor, exerts markedly cardio protective effects. Our recent data demonstrate that C1INH prevents vascular endothelial cell apoptosis and a "modified" form of the reactive center loop-cleaved, inactive C1INH (iC1INH) plays an anti-inflammatory role in endotoxin shock. The aim of this study was to determine whether C1INH protects against myocardial cell injury via an anti-apoptotic activity or anti-inflammatory effect. In a rat model of acute myocardial infarction (AMI) induced by I/R, administration of C1INH protected against cardiomyocytic apoptosis via normalization of ratio of the Bcl-2/ Bax expression in the myocardial infarct area. C1INH improved parameters of cardiac function and hemodynamics and reduced myocardial infarct size (MIS). In addition, myocardial and blood myeloperoxidase (MPO) activity, a marker of neutrophil infiltration, was decreased by treatment of C1INH. In cultured H9c2 rat cardiomyocytic cells, C1INH blocked hypoxia/reoxygenation-induced apoptosis in the absence of sera associated with inhibition of cytochrome c translocation and suppression of caspase-3 activation. The proportion of Bcl-2/Bax expression induced by hypoxia/reoxygenation was reversed by C1INH. Importantly, iC1INH also revealed these similar effects, indicating that C1INH has a direct anti-apoptotic activity. Therefore, these studies support the hypothesis that C1INH, in addition to inhibition of activation of the complement and contact systems, improves outcome in I/R-mediated myocardial cell injury via an anti-apoptotic activity independent of serine protease inhibitory activity. (c) 2006 Elsevier Inc. All rights reserved. C1 Wuhan Univ, Sch Med, Renmin Hosp, Dept Cardiol, Wuhan, Hubei, Peoples R China. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. Tufts Univ, Sch Med, Caritas St Elizabeths Med Ctr, Div Cardiovasc Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. Hubei Univ, Sch Life Sci, Wuhan, Hubei, Peoples R China. RP Lin, GS (reprint author), Wuhan Univ, Sch Med, Renmin Hosp, Dept Cardiol, Wuhan, Hubei, Peoples R China. EM lgs1027_phb@163.com; dliu@cbrinstitute.org NR 31 TC 28 Z9 33 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 OCT 20 PY 2006 VL 349 IS 2 BP 504 EP 512 DI 10.1016/j.bbrc.2006.08.065 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 088DN UT WOS:000240791800008 PM 16942749 ER PT J AU Bahn, E Siegert, S Pfander, T Kramer, ML Schulz-Schaeffer, WJ Hewett, JW Breakefield, XO Hedreen, JC Rostasy, KM AF Bahn, E. Siegert, S. Pfander, T. Kramer, M. L. Schulz-Schaeffer, W. J. Hewett, J. W. Breakefield, X. O. Hedreen, J. C. Rostasy, K. M. TI TorsinB expression in the developing human brain SO BRAIN RESEARCH LA English DT Article DE TorsinB brain; children; neuron; postnatal; dopaminergic ID PC12 CELLS; DYSTONIA; PROTEIN; GENE; DYT1; LOCALIZATION; AGGREGATION; SUPPRESSION; STRESS AB Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. The majority of cases are caused by a 3-bp deletion (GAG) in the coding region of the DYT1 (TOR1A) gene. The cellular and regional distribution of torsinA protein, which is restricted to neuronal cells and present in all brain regions by the age of 2 months has been described recently in human developing brain. TorsinB is a member of the same family of proteins and is highly homologous with its gene adjacent to that for torsinA on chromosome 9q34. TorsinA and torsinB share several remarkable features suggesting that they may interact in vivo. This study examined the expression of torsinB in the human brain of fetuses, infants and children up to 7 years of age. Our results indicate that torsinB protein expression is temporarily and spatially regulated in a similar fashion as torsinA. Expression of torsinB protein was detectable beginning at four to 8 weeks of age in the cerebellum (Purkinje cells), substantia nigra (dopaminergic neurons), hippocampus and basal ganglia and was predominantly restricted to neuronal cells. In contrast to torsinA, torsinB immunoreactivity was found more readily in the nuclear envelope. High levels of torsinB protein were maintained throughout infancy, childhood and adulthood suggesting that torsinB is also needed for developmental events occurring in the early postnatal phase and is necessary for functional activity throughout life. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Gottingen, Dept Pediat & Pediat Neurol, D-37073 Gottingen, Germany. Univ Gottingen, Dept Neuropathol, D-3400 Gottingen, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. RP Rostasy, KM (reprint author), Univ Gottingen, Dept Pediat & Pediat Neurol, Robert Koch Str 40, D-37073 Gottingen, Germany. EM Krostasy@excite.com NR 16 TC 6 Z9 6 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 OCT 20 PY 2006 VL 1116 BP 112 EP 119 DI 10.1016/j.brainres.2006.07.102 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 102EN UT WOS:000241793900013 PM 16938275 ER PT J AU Call, ME Schnell, JR Xu, CQ Lutz, RA Chou, JJ Wucherpfennig, KW AF Call, Matthew E. Schnell, Jason R. Xu, Chenqi Lutz, Regina A. Chou, James J. Wucherpfennig, Kai W. TI The structure of the zeta zeta transmembrane dimer reveals features essential for its assembly with the T cell receptor SO CELL LA English DT Article ID ISOTOPICALLY ENRICHED PROTEINS; ANTIGEN RECEPTOR; J-COUPLINGS; CHAIN DIMERIZATION; CHEMICAL-SHIFTS; CD3-ZETA CHAIN; ALPHA-HELICES; CD3 COMPLEX; ASSOCIATION; EXPRESSION AB The T cell receptor (TCR) alpha beta heterodimer communicates ligand binding to the cell interior via noncovalently associated CD3 gamma epsilon, CD3 delta epsilon, and xi xi dimers. While structures of extracellular components of the TCR-CD3 complex are known, the transmembrane (TM) domains that mediate assembly have eluded structural characterization. Incorporation of the xi xi signaling module is known to require one basic TCR alpha and two xi xi aspartic acid TM residues. We report the NMR structure of the xi xi(TM) dinner, a left-handed coiled coil with substantial polar contacts. Mutagenesis experiments demonstrate that three polar positions are critical for xi xi dimerization and assembly with TCR. The two aspartic acids create a single structural unit at the a interface stabilized by extensive hydrogen bonding, and there is evidence for a structural water molecule (or molecules) within close proximity. This structural unit, representing only the second transmembrane dinner interface solved to date, serves as a paradigm for the assembly of all modules involved in TCR signaling. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM james_chou@hms.harvard.edu; kai_wucherpfennig@dfci.harvard.edu RI Chou, James/N-9840-2013; OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [R01 AI054520]; NIBIB NIH HHS [EB002026, P41 EB002026]; PHS HHS [F32] NR 49 TC 131 Z9 135 U1 3 U2 27 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 20 PY 2006 VL 127 IS 2 BP 355 EP 368 DI 10.1016/j.cell.2006.08.044 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102QH UT WOS:000241827100022 PM 17055436 ER PT J AU St-Pierre, J Drori, S Uldry, M Silvaggi, JM Rhee, J Jager, S Handschin, C Zheng, KN Lin, JD Yang, WL Simon, DK Bachoo, R Spiegelman, BM AF St-Pierre, Julie Drori, Stavit Uldry, Marc Silvaggi, Jessica M. Rhee, James Jager, Sibylle Handschin, Christoph Zheng, Kangni Lin, Jiandie Yang, Wenli Simon, David K. Bachoo, Robert Spiegelman, Bruce M. TI Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators SO CELL LA English DT Article ID CONTROLLING MITOCHONDRIAL BIOGENESIS; HEPATIC GLUCONEOGENESIS; ENDOTHELIAL-CELLS; REDOX REGULATION; PGC-1-ALPHA; MUSCLE; MPTP; DISRUPTION; EXPRESSION; INDUCTION AB PPAR gamma coactivator 1 alpha (PGC-1 alpha) is a potent stimulator of mitochondrial biogenesis and respiration. Since the mitochondrial electron transport chain is the main producer of reactive oxygen species (ROS) in most cells, we examined the effect of PGC-1 alpha on the metabolism of ROS. PGC-1 alpha is coinduced with several key ROS-detoxifying enzymes upon treatment of cells with an oxidative stressor; studies with RNAi or null cells indicate that PGC-1 alpha is required for the induction of many ROS-detoxifying enzymes, including GPx1 and SOD2. PGC-1 alpha null mice are much more sensitive to the neurodegenerative effects of MPTP and kainic acid, oxidative stressors affecting the substantia. nigra and hippocampus, respectively. Increasing PGC-1 alpha levels dramatically protects neural cells in culture from oxidative-stressor-mediated death. These studies reveal that PGC-1 alpha is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Univ Montreal, Inst Rech Immunol & Canc, Pavill Marcelle Coutu,2950 Chem Polytech, Montreal, PQ H3T 1J4, Canada. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [DK54477, P30 DK040561, P30 DK040561-11]; NINDS NIH HHS [K02 NS4311] NR 42 TC 990 Z9 1019 U1 14 U2 79 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 20 PY 2006 VL 127 IS 2 BP 397 EP 408 DI 10.1016/j.cell.2006.09.024 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102QH UT WOS:000241827100025 PM 17055439 ER PT J AU El-Shewy, HM Johnson, KR Lee, MH Jaffa, AA Obeid, LM Luttrell, LM AF El-Shewy, Hesham M. Johnson, Korey R. Lee, Mi-Hye Jaffa, Ayad A. Obeid, Lina M. Luttrell, Louis M. TI Insulin-like growth factors mediate heterotrimeric G protein-dependent ERK1/2 activation by transactivating sphingosine 1-phosphate receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-I RECEPTOR; BC3H-1 MURINE MYOCYTES; MANNOSE 6-PHOSPHATE; SPHINGOSINE 1-PHOSPHATE; KINASE-C; FACTOR-II/MANNOSE-6-PHOSPHATE RECEPTOR; G(BETA-GAMMA) SUBUNITS; BETA-ARRESTIN; EGF RECEPTOR; CELLS AB Although several studies have shown that a subset of insulin-like growth factor (IGF) signals require the activation of heterotrimeric G proteins, the molecular mechanisms underlying IGF-stimulated G protein signaling remain poorly understood. Here, we have studied the mechanism by which endogenous IGF receptors activate the ERK1/2 mitogen-activated protein kinase cascade in HEK293 cells. In these cells, treatment with pertussis toxin and expression of a G alpha(q/11)-305-359) peptide that inhibits G(q/11) signaling additively inhibited IGF-stimulated ERK1/2 activation, indicating that the signal was almost completely G protein-dependent. Treatment with IGF-1 or IGF-2 promoted translocation of green fluorescent protein (GFP)-tagged sphingosine kinase (SK) 1 from the cytosol to the plasma membrane, increased endogenous SK activity within 30 s of stimulation, and caused a statistically significant increase in intracellular and extracellular sphingosine 1-phosphate (S1P) concentration. Using a GFP-tagged S1P(1) receptor as a biological sensor for the generation of physiologically relevant S1P levels, we found that IGF-1 and IGF-2 induced GFP-S1P receptor internalization and that the effect was blocked by pretreatment with the SK inhibitor, dimethylsphingosine. Treating cells with dimethylsphingosine, silencing SK1 expression by RNA interference, and blocking endogenous S1P receptors with the competitive antagonist VPC23019 all significantly inhibited IGF-stimulated ERK1/2 activation, suggesting that IGFs elicit G protein-dependent ERK1/2 activation by stimulating SK1-dependent transactivation of S1P receptors. Given the ubiquity of SK and S1P receptor expression, S1P receptor transactivation may represent a general mechanism for G protein-dependent signaling by non-G protein-coupled receptors. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,816 CSB,POB 250624, Charleston, SC 29425 USA. EM luttrell@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIDDK NIH HHS [DK58283]; NIGMS NIH HHS [GM62887] NR 58 TC 52 Z9 53 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 OCT 20 PY 2006 VL 281 IS 42 BP 31399 EP 31407 DI 10.1074/jbc.M605339200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094JI UT WOS:000241235300024 PM 16926156 ER PT J AU Kramer, HF Witczak, CA Taylor, EB Fujii, N Hirshman, MF Goodyear, LJ AF Kramer, Henning F. Witczak, Carol A. Taylor, Eric B. Fujii, Nobuharu Hirshman, Michael F. Goodyear, Laurie J. TI AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING-PROTEIN; GLUT4 TRANSLOCATION; TRANSPORT; PHOSPHORYLATION; EXERCISE; MICE; EXPRESSION; SUBSTRATE; GLYCOGEN; SIGNALS AB Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake. We recently identified the Rab GTPase-activating protein ( GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle. Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M). One week following gene injection, protein expression for all AS160 isoforms was elevated over 7-fold. To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [H-3]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively. Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160. However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity. Transfection with 4P mutant AS160 also significantly impaired contraction-stimulated glucose uptake, as did overexpression of wild type AS160. In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles. These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical. Our findings directly implicate AS160 as a critical convergence factor for independent stimulators of skeletal muscle glucose uptake. C1 Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Metab Sect, 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 [AR45670, AR051663, AR42238]; NIDDK NIH HHS [F32 DK075851] NR 30 TC 160 Z9 162 U1 1 U2 8 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 OCT 20 PY 2006 VL 281 IS 42 BP 31478 EP 31485 DI 10.1074/jbc.M605461200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094JI UT WOS:000241235300032 PM 16935857 ER PT J AU Lenz, HJ Van Cutsem, E Khambata-Ford, S Mayer, RJ Gold, P Stella, P Mirtsching, B Cohn, AL Pippas, AW Azarnia, N Tsuchihashi, Z Mauro, DJ Rowinsky, EK AF Lenz, Heinz-Josef Van Cutsem, Eric Khambata-Ford, Shirin Mayer, Robert J. Gold, Philip Stella, Philip Mirtsching, Barry Cohn, Allen L. Pippas, Andrew W. Azarnia, Nozar Tsuchihashi, Zenta Mauro, David J. Rowinsky, Eric K. TI Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; GENE COPY NUMBER; MONOCLONAL-ANTIBODY; SOMATIC MUTATIONS; CLINICAL-RESPONSE; EGFR MUTATIONS; SOLID TUMORS; G(1) ARREST; NECK-CANCER AB Purpose This multicenter study evaluated the antitumor activity of cetuximab, an immunoglobulin G1 antibody directed at the epidermal growth factor receptor ( EGFR), in metastatic colorectal carcinoma (CRC) refractory to irinotecan, oxaliplatin, and a fluoropyrimidine. It also evaluated the safety, pharmacokinetics, immunokinetics, and biologic determinants of activity. Patients and Methods Patients with metastatic CRC, whose tumors demonstrated EGFR immunostaining and were refractory to irinotecan, oxaliplatin, and fluoropyrimidines, were treated with cetuximab at a loading dose of 400 mg/m(2) followed by 250 mg/m(2) weekly. An independent review committee (IRC) reviewed responses. Blood was collected for cetuximab pharmacokinetics and to detect antibodies to cetuximab. EGFR gene sequencing of the tyrosine kinase domain and gene copy number assessments were performed. Results The response rates in 346 patients, as determined by the investigators and IRC, were 12.4% (95% CI, 9.1 to 16.4) and 11.6% ( 95% CI, 8.4 to 16.4). The median progression-free survival (PFS) and survival times were 1.4 months ( 95% CI, 1.4 to 2.1) and 6.6 months ( 95% CI, 5.6 to 7.6), respectively. An acneiform rash occurred in 82.9% of patients; grade 3 rash was observed in 4.9%. Response and survival related strongly to the severity of the rash. In contrast, clinical benefit did not relate to EGFR immunostaining. EGFR tyrosine kinase domain mutations were not identified, and EGFR gene copy number did not relate to response or PFS, but to survival ( P =.03). Conclusion Cetuximab is active and well tolerated in metastatic CRC refractory to irinotecan, oxaliplatin, and fluoropyrimidines. The severity of rash was related to efficacy. Neither EGFR kinase domain mutations nor EGFR gene amplification appear to be essential for response to cetuximab in this setting. C1 Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. Dana Farber Partners Canc Care, Boston, MA USA. Swedish Canc Inst, Seattle, WA USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. Ctr Oncol Res & Treatment, Dallas, TX USA. Rocky Mt Canc Ctr, Denver, CO USA. Lakeland Reg Canc Ctr, Lakeland, FL USA. Imclone Syst Inc, New York, NY USA. RP Rowinsky, EK (reprint author), Imclone Syst, 33 Imclone Dr, Branchburg, NJ 08876 USA. EM eric.rowinsky@imclone.com NR 57 TC 370 Z9 389 U1 0 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 OCT 20 PY 2006 VL 24 IS 30 BP 4914 EP 4921 DI 10.1200/JCO.2006.06.7595 PG 8 WC Oncology SC Oncology GA 098CF UT WOS:000241497900020 PM 17050875 ER PT J AU Lorenz, KA Lynn, J Dy, S Wilkinson, A Mularski, RA Shugarman, LR Hughes, R Asch, SM Rolon, C Rastegar, A Shekelle, PG AF Lorenz, Karl A. Lynn, Joanne Dy, Sydney Wilkinson, Anne Mularski, Richard A. Shugarman, Lisa R. Hughes, Rhonda Asch, Steven M. Rolon, Cony Rastegar, Afshin Shekelle, Paul G. TI Quality measures for symptoms and advance care planning in cancer: A systematic review SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Hospice-and-Palliative-Medicine CY FEB 08-11, 2006 CL Nashville, TN SP Amer Acad Hospice & Palliat Med ID HEALTH-ORGANIZATION GUIDELINES; PAIN MANAGEMENT; OF-LIFE; PALLIATIVE CARE; HOSPICE CARE; VALIDATION; RELIEF; END; IMPLEMENTATION; IMPROVEMENT AB Purpose Measuring quality of care for symptom management and ascertaining patient goals offers an important step toward improving palliative cancer management. This study was designed to identify systematically the quality measures and the evidence to support their use in pain, dyspnea, depression, and advance care planning (ACP), and to identify research gaps. Methods English-language documents were selected from MEDLINE, Cumulative Index to Nursing and Allied Health, PsycINFO ( 1995 to 2005); Internet-based searches; and contact with measure developers. We used terms for each domain to select studies throughout the cancer care continuum. We included measures that expressed a normative relationship to quality, specified the target population, and specified the indicated care. Dual data review and abstraction was performed by palliative care researchers describing populations, testing, and attributes for each measure. Results A total of 4,599 of 5,182 titles were excluded at abstract review. Of 537 remaining articles, 19 contained measures for ACP, six contained measures for depression, five contained measures for dyspnea, and 20 contained measures for pain. We identified 10 relevant measure sets that included 36 fully specified or fielded measures and 14 additional measures ( 16 for pain, five for dyspnea, four for depression, and 25 for ACP). Most measures were unpublished, and few had been tested in a cancer population. We were unable to describe the specifications of all measures fully and did not search for measures for pain and depression that were not cancer specific. Conclusion Measures are available for assessing quality and guiding improvement in palliative cancer care. Existing measures are weighted toward ACP, and more nonpain symptom measures are needed. Additional testing is needed before the measures are used for accountability, and basic research is required to address measurement when self-report is impaired. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. RAND, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. RP Lorenz, KA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM karl.lorenz@med.va.gov NR 45 TC 49 Z9 50 U1 0 U2 4 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 OCT 20 PY 2006 VL 24 IS 30 BP 4933 EP 4938 DI 10.1200/JCO.2006.06.8650 PG 6 WC Oncology SC Oncology GA 098CF UT WOS:000241497900023 PM 17050878 ER PT J AU Walensky, LD Pitter, K Morash, J Oh, KJ Barbuto, S Fisher, J Smith, E Verdine, GL Korsmeyer, SJ AF Walensky, Loren D. Pitter, Kenneth Morash, Joel Oh, Kyoung Joon Barbuto, Scott Fisher, Jill Smith, Eric Verdine, Gregory L. Korsmeyer, Stanley J. TI A stapled BID BH3 helix directly binds and activates BAX SO MOLECULAR CELL LA English DT Article ID MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; BH3-ONLY PROTEINS; PROAPOPTOTIC BAX; CHELATOR-LIPIDS; CYTOCHROME-C; BCL-W; APOPTOSIS; DEATH; BCL-X(L); FAMILY AB BAX is a multidomain proapoptotic BCL-2 family protein that resides in the cytosol until activated by an incompletely understood trigger mechanism, which facilitates BAX translocation to mitochondria and downstream death events. Whether BAX is activated by direct contact with select BH3-only members of the BCL-2 family is highly debated. Here we detect and quantify a direct binding interaction between BAX and a hydrocarbon-stapled BID BH3 domain, which triggers the functional activation of BAX at nanomolar doses in vitro. Chemical reinforcement of BID BH3 alpha helicity was required to reveal the direct BID BH3-BAX association. We confirm the specificity of this BH3 interaction by characterizing a stapled BAD BH3 peptide that interacts with antiapoptotic BCL-X(L) but does not bind or activate BAX. We further demonstrate that membrane targeting of stapled BID BH3 optimizes its ability to activate BAX, supporting a model in which BID directly engages BAX to trigger mitochondrial apoptosis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. RP Walensky, LD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM loren_walensky@dfci.harvard.edu FU NCI NIH HHS [5P01CA92625, 5R37CA050239]; NHLBI NIH HHS [K08 HL074049, K08HL074049] NR 52 TC 243 Z9 247 U1 0 U2 40 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 20 PY 2006 VL 24 IS 2 BP 199 EP 210 DI 10.1016/j.molcel.2006.08.020 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 101SF UT WOS:000241760100006 PM 17052454 ER PT J AU Hakre, S Tussie-Luna, MI Ashworth, T Novina, CD Settleman, J Sharp, PA Roy, AL AF Hakre, Shweta Tussie-Luna, Maria Isabel Ashworth, Todd Novina, Carl D. Settleman, Jeffrey Sharp, Phillip A. Roy, Ananda L. TI Opposing functions of TFII-I spliced lsoforms in growth factor-induced gene expression SO MOLECULAR CELL LA English DT Article ID SERUM RESPONSE FACTOR; C-FOS PROMOTER; RHO-FAMILY GTPASES; MAP KINASE; TRANSCRIPTIONAL ACTIVATION; HISTONE DEACETYLASE-3; NUCLEAR TRANSLOCATION; PHOSPHORYLATION; COMPLEXES; ELK-1 AB Multifunctional transcription factor TFII-I has two spliced isoforms (Delta and beta) in murine fibroblasts. Here we show that these isoforms have distinct subcellular localization and mutually exclusive transcription functions in the context of growth factor signaling. In the absence of signaling, TFII-I beta is nuclear and recruited to the c-fos promoter in vivo. But upon growth factor stimulation, the promoter recruitment is abolished and it is exported out of the nucleus. Moreover, isoform-specific silencing of TFII-I beta results in transcriptional activation of the c-fos gene. In contrast, TFII-I Delta is largely cytoplasmic in the resting state but translocates to the nucleus upon growth factor signaling, undergoes signal-induced recruitment to the same site on the c-fos promoter, and activates the gene. Importantly, activated TFII-I Delta interacts with Erk1/2 (MAPK) kinase in the cell cytoplasm and imports the Erk1/2 to the nucleus, thereby transducing growth factor signaling. Our results identify a unique growth factor signaling pathway controlled by opposing activities of two TFII-I spliced isoforms. C1 Tufts Univ, Sch Med, Program Immunol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Genet Program, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. RP Roy, AL (reprint author), Tufts Univ, Sch Med, Program Immunol, 150 Harrison Ave, Boston, MA 02111 USA. EM ananda.roy@tufts.edu FU NCI NIH HHS [CA062142, P01-CA42063, P30-CA14051]; NIAID NIH HHS [AI45150]; NIGMS NIH HHS [R37-GM34277] NR 31 TC 32 Z9 32 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 20 PY 2006 VL 24 IS 2 BP 301 EP 308 DI 10.1016/j.molcel.2006.09.005 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 101SF UT WOS:000241760100015 PM 17052463 ER PT J AU Zhang, H Hoffmann, F He, J He, X Kankasa, C West, JT Mitchell, CD Ruprecht, RM Orti, G Wood, C AF Zhang, Hong Hoffmann, Federico He, Jun He, Xiang Kankasa, Chipepo West, John T. Mitchell, Charles D. Ruprecht, Ruth M. Orti, Guillermo Wood, Charles TI Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODY-RESPONSES; VERTICAL TRANSMISSION; NONPROGRESSIVE INFECTION; HIV-1-INFECTED INFANTS; ACUTE SEROCONVERSION; MACROPHAGE TROPISM; TYPE-1 INFECTION; VIRAL PHENOTYPE; CELL TROPISM AB Background: The causal mechanisms of differential disease progression in HIV-1 infected children remain poorly defined, and much of the accumulated knowledge comes from studies of subtype B infected individuals. The applicability of such findings to other subtypes, such as subtype C, remains to be substantiated. In this study, we longitudinally characterized the evolution of the Env V1-V5 region from seven subtype C HIV-1 perinatally infected children with different clinical outcomes. We investigated the possible influence of viral genotype and humoral immune response on disease progression in infants. Results: Genetic analyses revealed that rapid progressors (infants that died in the first year of life) received and maintained a genetically homogeneous viral population throughout the disease course. In contrast, slow progressors (infants that remained clinically asymptomatic for up to four years) also exhibited low levels variation initially, but attained higher levels of diversity over time. Genetic assessment of variation, as indicated by dN/ dS, showed that particular regions of Env undergo selective changes. Nevertheless, the magnitude and distribution of these changes did not segregate slow and rapid progressors. Longitudinal trends in Env V1-V5 length and the number of potential N-glycosylation sites varied among patients but also failed to discriminate between fast and slow progressors. Viral isolates from rapid progressors and slow progressors displayed no significant growth properties differences in vitro. The neutralizing activity in maternal and infant baseline plasma also varied in its effectiveness against the initial virus from the infants but did not differentiate rapid from slow progressors. Quantification of the neutralization susceptibility of the initial infant viral isolates to maternal baseline plasma indicated that both sensitive and resistant viruses were transmitted, irrespective of disease course. We showed that humoral immunity, whether passively acquired or developed de novo in the infected children, varied but was not predictive of disease progression. Conclusion: Our data suggest that neither genetic variation in env, or initial maternal neutralizing activity, or the level of passively acquired neutralizing antibody, or the level of the de novo neutralization response appear to be linked to differences in disease progression in subtype C HIV-1 infected children. C1 Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68583 USA. Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. Univ Teaching Hosp, Dept Pediat, Lusaka, Zambia. Univ Miami, Sch Med, Dept Pediat, Miami, FL 33152 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wood, C (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68583 USA. EM hongz@unlserve.unl.edu; federico@unlserve.unl.edu; jhe1@unl.edu; xhe@unlserve.unl.edu; ckankasa@zamnet.zm; john-west@ouhsc.edu; cmitchel@med.miami.edu; ruth_ruprecht@dfci.harvard.edu; gorti@unl.edu; cwood1@unl.edu FU FIC NIH HHS [D43 TW001429, TW01429]; NCI NIH HHS [CA76958]; NCRR NIH HHS [RR15635, P20 RR015635]; NIAID NIH HHS [P01 AI048240, P01 AI 48240]; NICHD NIH HHS [R01 HD039620, HD39620] NR 75 TC 35 Z9 37 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD OCT 20 PY 2006 VL 3 AR 73 DI 10.1186/1742-4690-3-73 PG 15 WC Virology SC Virology GA 103JN UT WOS:000241881600002 PM 17054795 ER PT J AU Ho, PM Rumsfeld, JS AF Ho, P. Michael Rumsfeld, John S. TI Beyond inpatient and outpatient care: alternative model for hypertension management SO BMC PUBLIC HEALTH LA English DT Editorial Material ID BLOOD-PRESSURE AB Hypertension is a major contributor to worldwide cardiovascular mortality, however, only one-third of patients with hypertension have their blood pressure treated to guideline recommended levels. To improve hypertension control, there may need to be a fundamental shift in care delivery, one that is population-based and simultaneously addresses patient, provider and system barriers. One potential approach is home-based disease management, based on the triad of home monitoring, team care, and patient self-care. Although there may be challenges to achieving the vision of home-based disease management, there are tremendous potential benefits of such an approach for reducing the global burden of cardiovascular disease. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. RP Ho, PM (reprint author), Denver VA Med Ctr, Cardiol Sect, 1055 Clermont St 111B, Denver, CO 80220 USA. EM Michael.Ho@UCHSC.edu; John.Rumsfeld@va.gov NR 7 TC 11 Z9 12 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD OCT 19 PY 2006 VL 6 AR 257 DI 10.1186/1471-2458-6-257 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 098JQ UT WOS:000241517200001 PM 17052330 ER PT J AU Yelin, D Rizvi, I White, WM Motz, JT Hasan, T Bouma, BE Tearney, GJ AF Yelin, D. Rizvi, I. White, W. M. Motz, J. T. Hasan, T. Bouma, B. E. Tearney, G. J. TI Three-dimensional miniature endoscopy SO NATURE LA English DT Article ID INTRADUCTAL LESIONS; DIAGNOSIS; BREAST C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yelin, D (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM gtearney@partners.org OI Rizvi, Imran/0000-0001-9673-4700 NR 10 TC 84 Z9 87 U1 1 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 19 PY 2006 VL 443 IS 7113 BP 765 EP 765 DI 10.1038/443765a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 096FJ UT WOS:000241362700033 PM 17051200 ER PT J AU Bussel, JB Kuter, DJ George, JN McMillan, R Aledort, LM Conklin, GT Lichtin, AE Lyons, RM Nieva, J Wasser, JS Wiznitzer, I Kelly, R Chen, CF Nichol, JL AF Bussel, James B. Kuter, David J. George, James N. McMillan, Robert Aledort, Louis M. Conklin, George T. Lichtin, Alan E. Lyons, Roger M. Nieva, Jorge Wasser, Jeffrey S. Wiznitzer, Israel Kelly, Reggie Chen, Chien-Feng Nichol, Janet L. TI AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IDIOPATHIC THROMBOCYTOPENIC PURPURA; MEGAKARYOCYTE GROWTH; IN-VITRO; PLATELET PRODUCTION; APLASTIC-ANEMIA; CHEMOTHERAPY; DESTRUCTION; ANTIBODIES; MEGAKARYOPOIESIS; AUTOANTIBODIES AB BACKGROUND Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP. METHODS In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 microg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 microg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment. RESULTS No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 microg of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 microg of AMG 531 per cubic millimeter, respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 microg of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-microg dose, the 3-microg dose, and placebo, respectively. CONCLUSIONS AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. C1 New York Presbyterian Hosp, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oklahoma, Med Ctr, Oklahoma City, OK USA. Scripps Canc Ctr, La Jolla, CA USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Diagnost Clin Houston, Houston, TX USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Hematol Oncol Associates S Texas, San Antonio, TX USA. DeQuattro Community Canc Ctr, Manchester, CT USA. Broward Gen Med Ctr, Ft Lauderdale, FL USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Bussel, JB (reprint author), Weill Cornell Univ, Div Pediat Hematol, Payson 609,525 E 68th St, New York, NY 10021 USA. EM jbussel@med.cornell.edu NR 34 TC 266 Z9 278 U1 1 U2 5 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 OCT 19 PY 2006 VL 355 IS 16 BP 1672 EP 1681 DI 10.1056/NEJMoa054626 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 096DN UT WOS:000241357300008 PM 17050891 ER PT J AU Fraser, IP Cserti, CM Dzik, WH Pasternack, MS Harris, NL AF Fraser, Iain P. Cserti, Christine M. Dzik, Walter H. Pasternack, Mark S. Harris, Nancy Lee TI A 3-year-old girl with fever after a visit to Africa - Severe Plasmodium falciparum malaria SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EXCHANGE-TRANSFUSION; TRAVELERS; CYTOADHERENCE; ERYTHROCYTES; DIAGNOSIS; PROGNOSIS; SPECTRUM; CHILDREN; ADJUNCT; DISEASE C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Fraser, IP (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 22 TC 9 Z9 9 U1 1 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 OCT 19 PY 2006 VL 355 IS 16 BP 1715 EP 1722 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 096DN UT WOS:000241357300014 PM 17050896 ER PT J AU Freilinger, A Rosner, M Krupitza, G Nishino, M Lubec, G Korsmeyer, SJ Hengstschlager, M AF Freilinger, A. Rosner, M. Krupitza, G. Nishino, M. Lubec, G. Korsmeyer, S. J. Hengstschlaeger, M. TI Tuberin activates the proapoptotic molecule BAD SO ONCOGENE LA English DT Article DE TSC2; tuberin; BAD; apoptosis ID TUMOR-SUPPRESSOR GENE; B-CELL LYMPHOMA; SCLEROSIS COMPLEX; 3-KINASE/AKT PATHWAY; HUMAN-DISEASE; SURVIVAL; TSC2; PRODUCT; PHOSPHORYLATION; IDENTIFICATION AB TSC1, encoding hamartin, and TSC2, encoding tuberin, are tumor suppressor genes responsible for the autosomal dominantly inherited disease tuberous sclerosis (TSC). TSC affects similar to 1 in 6000 individuals and is characterized by the development of tumors, named hamartomas, in different organs. Hamartin and tuberin form a complex, of which tuberin is assumed to be the functional component. The TSC proteins have been implicated in the control of cell cycle and cell size. In addition to enhanced growth, reduced death rates can lead to tumor development. Therefore, defects in the apoptosis-inducing pathways contribute to neoplastic cell expansion. Here, we show that tuberin triggers apoptosis, accompanied by downregulation of p70S6K activity and of phosphorylation of BAD on residue Ser136, and by upregulation of the interaction of BAD/BCL-2 and BAD/BCL-X-L. AKT phosphorylation negatively regulates tuberin's potential to trigger apoptosis. Experiments with BAD-/- cells demonstrate BAD to be a mediator of tuberin's effects on the regulation of apoptosis. Tuberin interferes with insulin-like growth factor-1-induced BAD Ser136 phosphorylation and cell survival. Our work proposes a model in which tuberin-mediated inhibition of p70S6K activates BAD to heterodimerize with BCL-2 and BCL-XL to promote apoptosis. A mutation of TSC2 - as it occurs in TSC patients - attenuates this proapoptotic potential, underscoring the relevance of our findings for human pathophysiology. C1 Med Univ Vienna, Gen Hosp, A-1090 Vienna, Austria. Med Univ Vienna, Inst Clin Pathol, Vienna, Austria. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Med, Boston, MA USA. Med Univ Vienna, Dept Pediat, Vienna, Austria. RP Hengstschlager, M (reprint author), Med Univ Vienna, Gen Hosp, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM markus.hengstschlaeger@meduniwien.ac.at OI Krupitza, Georg/0000-0003-2949-7906; Lubec, Gert/0000-0002-6333-9461 NR 42 TC 34 Z9 34 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 19 PY 2006 VL 25 IS 49 BP 6467 EP 6479 DI 10.1038/sj.onc.1209660 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 096RS UT WOS:000241395100003 PM 16702951 ER PT J AU Becerra, L Morris, S Bazes, S Gostic, R Sherman, S Gostic, J Pendse, G Moulton, E Scrivani, S Keith, D Chizh, B Borsook, D AF Becerra, Lino Morris, Susie Bazes, Shelly Gostic, Richard Sherman, Seth Gostic, Julie Pendse, Gautam Moulton, Eric Scrivani, Steven Keith, David Chizh, Boris Borsook, David TI Trigeminal neuropathic pain alters responses in CNS circuits to mechanical (brush) and thermal (cold and heat) stimuli SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brainstem; caudate; dorsal horn; facial; neuropathology; noxious; pain; peripheral nerve; phenotype; prefrontal cortex; somatosensory cortex; trigeminal ID BASAL GANGLIA; HUMAN BRAIN; EVOKED ALLODYNIA; OROFACIAL PAIN; NOXIOUS HEAT; ACTIVATION; FMRI; SYSTEM; REPRESENTATION; STRIATUM AB Functional magnetic resonance imaging was used to study patients with chronic neuropathic pain involving the maxillary region (V2) of the trigeminal nerve in patients with spontaneous pain and evoked pain to brush (allodynia). Patients underwent two functional scans (2-3 months apart) with mechanical and thermal stimuli applied to the affected region of V2 and to the mirror site in the unaffected contralateral V2 region, as well as bilaterally to the mandibular (V3) division. Patients were stimulated with brush, noxious cold, and noxious heat. Significant changes were observed in regions within and outside the primary trigeminal sensory pathway. Stimulation to the affected ( neuropathic) side resulted in predominantly frontal region and basal ganglia activation compared with the control side. The differences were consistent with the allodynia to brush and cold. A region of interest-based analysis of the trigeminal sensory pathway revealed patterns of activation that differentiated between the affected and unaffected sides and that were particular to each stimulus. Activation in the spinal trigeminal nucleus was constant in location for all pain stimuli. Activation in other brainstem nuclei also showed differences in the blood oxygenation level-dependent signal for the affected versus the unaffected side. Thus, sensory processing in patients with trigeminal neuropathic pain is associated with distinct activation patterns consistent with sensitization within and outside of the primary sensory pathway. C1 McLean Hosp, Pain & Analgesia Imaging & Neurosci Grp, Dept Psychiat, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Dent Med, Craniofacial Pain Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02116 USA. GlaxoSmithKline Inc, Clin Pharmacol & Discovery Med, Cambridge CB2 2GG, England. RP Borsook, D (reprint author), Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Boston, MA 02115 USA. EM dborsook@mclean.harvard.edu FU NIDA NIH HHS [NS1R01DA14178]; NINDS NIH HHS [NS042721] NR 58 TC 111 Z9 114 U1 2 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 OCT 18 PY 2006 VL 26 IS 42 BP 10646 EP 10657 DI 10.1523/JNEUROSCI.2305-06.2006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 101GE UT WOS:000241727300008 PM 17050704 ER PT J AU van Kimmenade, RRJ Januzzi, JL Baggish, AL Lainchbury, JG Bayes-Genis, A Richards, AM Pinto, YM AF van Kimmenade, Roland R. J. Januzzi, James L., Jr. Baggish, Aaron L. Lainchbury, John G. Bayes-Genis, Antoni Richards, A. Mark Pinto, Yigal M. TI Amino-terminal pro-brain natriuretic peptide, renal function, and outcomes in acute heart failure - Redefining the cardiorenal interaction? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID EMERGENCY-DEPARTMENT PRIDE; VENTRICULAR DYSFUNCTION; UREMIC PATIENTS; NT-PROBNP; DIAGNOSIS; INSUFFICIENCY; CREATININE; DYSPNEA; CARVEDILOL; PREDICTION AB OBJECTIVES We sought to study the individual and integrative role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and parameters of renal function for prognosis in heart failure. BACKGROUND Amino-terminal pro-BNP and renal impairment both predict death in patients with heart failure. Worsening of renal function in heart failure even defines the "cardiorenal syndrome." METHODS Seven hundred twenty subjects presenting with acute heart failure from 4 university-affiliated medical centers were dichotomized according to NT-proBNP concentration and baseline glomerular filtration rate. In addition, patients were divided according to changes in renal function. The primary end point was 60-day mortality. RESULTS The combination of a glomerular filtration rate (GFR) < 60 ml/min/1.73 m(2) with an NT-proBNP > 4,647 pg/ml was the best predictor of 60-day mortality (odds ratio 3.46; 95% confidence interval 2.13 to 5.63). Among subjects with an NT-proBNP above the median, those with a GFR < 60 ml/min/1.73 M-2 or a creatinine rise >= 0.3 mg/dl had the worst prognosis, whereas in subjects with a NT-proBNP below the median, prognosis was not influenced by either impaired renal function at presentation or the development of renal impairment during admission. CONCLUSIONS The combination of NT-proBNP with measures of renal function better predicts short-term outcome in acute heart failure than either parameter alone. Among heart failure patients, the seems more useful to delineate the "cardiorenal syndrome" than the previous criteria of a clinical diagnosis of heart failure. C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. Christchurch Sch Med & Hlth Sci, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. Hosp Santa Cruz & San Pablo, Dept Cardiol, E-08025 Barcelona, Spain. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Yawkey 5800,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; NR 36 TC 93 Z9 99 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 17 PY 2006 VL 48 IS 8 BP 1621 EP 1627 DI 10.1016/j.jacc.2006.06.056 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 096ZC UT WOS:000241414600016 PM 17045898 ER PT J AU Laudanski, K Miller-Graziano, C Xiao, WZ Mindrinos, MN Richards, DR De, A Moldawer, LL Maier, RV Bankey, P Baker, HV Brownstein, BH Cobb, JP Calvano, SE Davis, RW Tompkins, RG AF Laudanski, Krzysztof Miller-Graziano, Carol Xiao, Wenzhong Mindrinos, Michael N. Richards, Daniel R. De, Asit Moldawer, Lyle L. Maier, Ronald V. Bankey, Paul Baker, Henry V. Brownstein, Bernard H. Cobb, J. Perren Calvano, Steve E. Davis, Ronald W. Tompkins, Ronald G. CA Inflammation Host Response Injury TI Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anergy; apoptosis; costimulatory receptors; immunosuppression; network analysis ID MULTIPLE ORGAN DYSFUNCTION; NEGATIVE REGULATION; DENDRITIC CELLS; DOWN-REGULATION; ACTIVATION; RECEPTOR; DEATH; DISEASE; SEPSIS; DIFFERENTIATION AB Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for the future of medicine. Patients with injuries severe enough to develop multiple organ dysfunction syndrome have multiple immune derangements, including T cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers an opportunity to discover leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in T cell (5,693 genes), monocyte (2,801 genes), and total leukocyte (3,437 genes) transcriptomes, with only 911 of these genes common to all three cell populations (12%). T cell-specific pathway analyses identified increased gene expression of several inhibitory receptors (PD-1, CD152, NRP-1, and Lag3) and concomitant decreases in stimulatory receptors (CD28, CD4, and IL-2R alpha). Functional analysis of T cells and monocytes confirmed reduced T cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly enriched cell populations combined with knowledge-based pathway analyses leads to the identification of regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell-specific pathway analyses can be used to discover pathway alterations in human disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Ingenu Syst Inc, Redwood City, CA 94063 USA. Stanford Gen Technol Ctr, Palo Alto, CA 94304 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Univ Washington, Dept Surg, Harborview Med Ctr, Seattle, WA 98104 USA. Washington Univ, Dept Radiat Oncol, St Louis, MO 63110 USA. Washington Univ, Dept Surg, St Louis, MO 63110 USA. Univ Rochester, Sch Med, Dept Surg, Rochester, NY 14642 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08903 USA. RP Tompkins, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. EM rtompkins@partners.org OI Laudanski, Krzysztof /0000-0002-7373-0851; xiao, wenzhong/0000-0003-4944-6380; Baker, Henry/0000-0002-8273-5320 FU NIGMS NIH HHS [5R01 GM-65237, R01 GM065237, U54 GM-62119, U54 GM062119] NR 36 TC 64 Z9 66 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 17 PY 2006 VL 103 IS 42 BP 15564 EP 15569 DI 10.1073/pnas.0607028103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200053 PM 17032758 ER PT J AU Berkowitz, MJ Picard, MH Harkness, S Sanborn, TA Hochman, JS Slater, JN AF Berkowitz, M. Joshua Picard, Michael H. Harkness, Shannon Sanborn, Timothy A. Hochman, Judith S. Slater, James N. TI Echocardiographic and angiographic correlations in patients with cardiogenic shock secondary to acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ISCHEMIC MITRAL REGURGITATION; EARLY REVASCULARIZATION; MECHANISM; SURVIVAL; TRIAL; MANAGEMENT AB In patients with cardiogenic shock (CS) complicating acute myocardial infarction, echocardiographic and angiographic findings are used to aid diagnosis, determine prognosis, and guide management. The purpose of this analysis from the Should we emergently revascularize Occluded Coronary arteries for Cardiogenic ShocK (SHOCK) trial is to identify relations between the angiographic and echocardiographic features of patients with CS. Such an analysis of the correlations between echocardiographic and angiographic findings in patients with CS may provide insights into the etiology and treatment of CS. In 302 randomized patients, an echocardiogram and an angiogram before revascularization were available in 127 patients. Although the median ejection fraction derived by echocardiography and left ventricular angiography was identical (30%), the positive correlation was weak (R-2 = 0.209, p = 0.019). Patients with a larger number of diseased vessels had worse mitral regurgitation (MR) by echocardiography (p = 0.005). There was a significant but weak association between left ventricular angiographic MR grade and echocardiographic MR severity (R-2 = 0.162, p = 0.015), but there was no association between culprit vessel and degree of MR. In conclusion, worse coronary artery disease is associated with more severe MR. Echocardiography and angiography are valuable and result in similar estimated ejection fractions in a large cohort, but there is wide variation between the techniques in patients. (c) 2006 Elsevier Inc. All rights reserved. C1 NYU, Sch Med, Cardiovasc Clin Res Ctr, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Res Inst, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. RP Berkowitz, MJ (reprint author), NYU, Sch Med, Cardiovasc Clin Res Ctr, New York, NY USA. EM mjoshb@cox.net OI Slater, James/0000-0003-3888-0317; Picard, Michael/0000-0002-9264-3243; Hochman, Judith/0000-0002-5889-5981 FU NHLBI NIH HHS [R01-HL49970, R01-HL50020] NR 14 TC 1 Z9 1 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 OCT 15 PY 2006 VL 98 IS 8 BP 1004 EP 1008 DI 10.1016/j.amjcard.2006.05.014 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097DS UT WOS:000241427400003 PM 17027560 ER PT J AU Rooks, DS Huang, J Bierbaum, BE Bolus, SA Rubano, J Connolly, CE Alpert, S Iversen, MD Katz, JN AF Rooks, Daniel S. Huang, Jie Bierbaum, Benjamin E. Bolus, Sarah A. Rubano, James Connolly, Christine E. Alpert, Sandra Iversen, Maura D. Katz, Jeffrey N. TI Effect of preoperative exercise on measures of functional status in men and women undergoing total hip and knee arthroplasty SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE total joint replacement; exercise; osteoarthritis; presurgical ID SURGEON PROCEDURE VOLUME; QUALITY-OF-LIFE; CARDIOVASCULAR FITNESS; PHYSICAL-ACTIVITY; AEROBIC EXERCISE; MUSCLE STRENGTH; OLDER-ADULTS; OSTEOARTHRITIS; OUTCOMES; REPLACEMENT AB Objective. To evaluate the effect of a short preoperative exercise intervention on the functional status, pain, and muscle strength of patients before and after total joint arthroplasty. Methods. A total of 108 men and women scheduled for total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to a 6-week exercise or education (control) intervention immediately prior to surgery. We assessed outcomes through questionnaires and performance measures. Analyses examined differences between groups over the preoperative and immediate postoperative periods and at 8 and 26 weeks postsurgery. Results. Among THA patients, the exercise intervention was associated with improvements in preoperative Western Ontario and McMaster Universities Osteoarthritis Index function score (improvement of 2.2 in exercisers versus decline of 3.9 in controls; P = 0.02) and Short Form 36 physical function score (decline of 0.4 in exercisers versus decline of 14.3 in controls; P = 0.003). No significant differences were. seen in TKA patients. Exercise participation increased muscle strength preoperatively (18% in THA patients and 20% in TKA patients), whereas the control patients had essentially no change in strength (P > 0.05 for exercise versus education in both THA and TKA groups). Exercise participation prior to total joint arthroplasty substantially reduced the risk of discharge to a rehabilitation facility in THA and TKA patients (adjusted odds ratio 0.27, 95% confidence interval 0.074-0.998). The intervention had no effects on outcomes 8 and 26 weeks postoperatively. Conclusion. A 6-week presurgical exercise program can safely improve preoperative functional status and muscle strength levels in persons undergoing THA. Additionally, exercise participation prior to total joint arthroplasty dramatically reduces the odds of inpatient rehabilitation. C1 Beth Israel Deaconess Med Ctr, New England Baptist Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Rooks, DS (reprint author), Beth Israel Deaconess Med Ctr, Feldberg Bldg,330 Brookline Ave, Boston, MA 02215 USA. EM drooks@bidmc.harvard.edu RI iversen, maura/O-5388-2015 OI iversen, maura/0000-0003-4708-9914 FU NCRR NIH HHS [RR-01032]; NIAMS NIH HHS [K23-AR-48305, K24-AR-02123, P60-AR-47782] NR 36 TC 105 Z9 110 U1 2 U2 21 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD OCT 15 PY 2006 VL 55 IS 5 BP 700 EP 708 DI 10.1002/art.22223 PG 9 WC Rheumatology SC Rheumatology GA 094QY UT WOS:000241255300004 PM 17013852 ER PT J AU Taylor, SE Lehman, BJ Kiefe, CI Seeman, TE AF Taylor, Shelley E. Lehman, Barbara J. Kiefe, Catarina I. Seeman, Teresa E. TI Relationship of early life stress and psychological functioning to adult C-reactive protein in the coronary artery risk development in young adults study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE stress; family; health; SES; comorbidities; HPA ID SOCIOECONOMIC-STATUS; CARDIOVASCULAR-DISEASE; INFLAMMATORY MARKERS; FAMILY ENVIRONMENT; LINKING DEPRESSION; PHYSICAL HEALTH; ASSOCIATION; METAANALYSIS; EXPRESSION; MEDIATORS AB Background: Low socioeconomic status (SES) and a harsh family environment in childhood have been linked to mental and physical health disorders in adulthood. The objective of the present investigation was to evaluate a developmental model of pathways that may help explain these links and to relate them to C-reactive protein (CRP) in the Coronary Artery Risk Development in Young Adults (CARDIA) dataset. Methods: Participants (n = 3248) in the CARDLA study, age 32 to 47 years, completed measures of childhood SES(CSES), early family environment (risky families [RF]), adult psychosocial functioning (PsyF, a latent factor measured by depression, mastery, and positive and negative social contacts), body mass index (BMI), and C-reactive protein. Results: Structural equation modeling indicated that CSES and RF are associated with C-reactive protein via their association with PsyF (standardized path coefficients: CSES to RF, RF to PsyF, PsyF to CRP, CSES to CRI all p < .05), with good overall modelfit. The association between PsyF and CRP was partially mediated by BMI (PsyF to BMI, BMI to CRP, both p < .05). Conclusions: Low childhood SES and a harsh early family environment appear to be related to elevated C-reactive protein in adulthood through pathways involving psychosocial dysfunction and high body mass index. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Geriatr, Los Angeles, CA 90095 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Taylor, SE (reprint author), Univ Calif Los Angeles, Dept Psychol, 1282A Franz Hall,405 Hilgard Ave, Los Angeles, CA 90095 USA. EM taylors@psych.ucla.edu FU NHLBI NIH HHS [N01-HC-05187, N01-HC-45134, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095]; NIMH NIH HHS [MH15750, R01-MH56880-05] NR 39 TC 136 Z9 138 U1 0 U2 12 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 OCT 15 PY 2006 VL 60 IS 8 BP 819 EP 824 DI 10.1016/j.biopsych.2006.03.016 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 094UH UT WOS:000241264100007 PM 16712805 ER PT J AU Hirano, N Butler, MO Xia, ZN Berezovskaya, A Murray, AP Ansen, S Kojima, S Nadler, LM AF Hirano, Naoto Butler, Marcus O. Xia, Zhinan Berezovskaya, Alla Murray, Andrew P. Ansen, Sascha Kojima, Seiji Nadler, Lee M. TI Identification of an immunogenic CD8(+) T-cell epitope derived from gamma-globin, a putative tumor-associated antigen for juvenile myelomonocytic leukemia SO BLOOD LA English DT Article ID TELOMERASE REVERSE-TRANSCRIPTASE; DISTINCT PROTEOLYTIC PROCESSES; CHRONIC MYELOID-LEUKEMIA; LYMPHOCYTE EPITOPE; BINDING PEPTIDES; CANCER; TRANSPLANTATION; GENERATION; MELANOMA; CHILDREN AB Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder. Although allogeneic stem cell transplantation can induce long-term remissions, relapse rates remain high and innovative approaches are needed. Since donor lymphocyte infusions have clinical activity in JMMIL, T-cell-mediated immunotherapy could provide a nonredundant treatment approach to compliment current therapies. gamma-Globin, an oncofetal protein overexpressed by clonogenic JMML cells, may serve as a target of an antitumor immune response. We predicted 5 gamma-globin-derived peptides as potential human leukocyte antigen (HLA)-A2 restricted cytotoxic T lymphocyte (CTL) epitopes and showed that 4 (g031, g071, g105, and g106) bind A2 molecules in vitro. Using an artificial antigen-presenting cell (aAPC) that can process both the N- and C-termini of endogenously expressed proteins, we biochemically confirmed that g105 is naturally processed and presented by cell surface A2. Furthermore, g105-specific CD8(+) CTLs generated from A2-positive healthy donors were able to specifically cytolyze gamma-globin(+), but not gamma-globin(-) JMML cells in an A2-restricted manner. These results suggest that this aAPC-based approach enables the biochemical identification of CD8(+) T-cell epitopes that are processed and presented by intact cells, and that CTL immunotherapy of JMML could be directed against the gamma-globin-derived epitope g105. 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, Dept Med, Boston, MA USA. Nagoya Univ, Dept Pediat, Nagoya, Aichi, Japan. RP Hirano, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM naoto_hirano@dfci.harvard.edu RI Kojima, Seiji/I-1601-2012 FU NCI NIH HHS [CA 87720, CA 92625-04]; NHLBI NIH HHS [HL 54785-08] NR 39 TC 13 Z9 16 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 OCT 15 PY 2006 VL 108 IS 8 BP 2662 EP 2668 DI 10.1182/blood-2006-04-017566 PG 7 WC Hematology SC Hematology GA 092XT UT WOS:000241131700033 PM 16778141 ER PT J AU Dose, M Khan, I Guo, ZY Kovalovsky, D Krueger, A von Boehmer, H Khazaie, K Gounari, F AF Dose, Marei Khan, Irum Guo, Zhuyan Kovalovsky, Damian Krueger, Andreas von Boehmer, Harald Khazaie, Khashayarsha Gounari, Fotini TI c-Myc mediates pre-TCR-induced proliferation but not developmental progression SO BLOOD LA English DT Article ID T-CELL-DEVELOPMENT; RNA-POLYMERASE-I; LYMPHOCYTE DEVELOPMENT; THYMOCYTE DEVELOPMENT; TRANSCRIPTION FACTOR; IMMATURE THYMOCYTES; GENOMIC TARGETS; GENE-EXPRESSION; BETA-SELECTION; RIBOSOMAL DNA AB Constitutive and cell-autonomous signals emanating from the pre-T-cell receptor (pre-TCR) promote proliferation, survival and differentiation of immature thymocytes. We show here that induction of pre-TCR signaling resulted in rapid elevation of c-Myc protein levels. Cre-mediated thymocyte-specific ablation of c-Myc in CD25(+)CD44(-) thymocytes reduced proliferation and cell growth at the pre-TCR checkpoint, resulting in thymic hypocellularity and a severe reduction in CD4(+)CD8(+) thymocytes. In contrast, c-Myc deficiency did not inhibit pre-TCR-mediated differentiation or survival. Myc(-/-) double-negative (DN) 3 cells progressed to the double-positive (DID) stage and up-regulated TCR alpha beta surface expression in the absence of cell proliferation, in vivo as well as in vitro. These observations indicate that distinct signals downstream of the pre-TCR are responsible for proliferation versus differentiation, and demonstrate that c-Myc is only required for pre-TCR-induced proliferation but is dispensable for developmental progression from the DN to the DP stage. C1 Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Gounari, F (reprint author), Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, 750 Washington St,Tufts NEMC 5602, Boston, MA 02111 USA. EM fgounari@tufts-nemc.org RI Krueger, Andreas/B-9427-2009; OI Krueger, Andreas/0000-0001-7873-7334; Dose, Marei/0000-0001-5394-9779 FU NIAID NIH HHS [R01 AI059676, R01 AI 059676-01] NR 73 TC 57 Z9 57 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 OCT 15 PY 2006 VL 108 IS 8 BP 2669 EP 2677 DI 10.1182/blood-2006-02-005900 PG 9 WC Hematology SC Hematology GA 092XT UT WOS:000241131700034 PM 16788099 ER PT J AU Ma, YP Cui, W Yang, JC Qu, J Di, CH Amin, HM Lai, R Ritz, J Krause, DS Chai, L AF Ma, Yupo Cui, Wei Yang, Jianchang Qu, Jun Di, Chunhui Amin, Hesham M. Lai, Raymond Ritz, Jerome Krause, Diane S. Chai, Li TI SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice SO BLOOD LA English DT Article ID CATENIN SIGNALING PATHWAY; TOWNES-BROCKS-SYNDROME; BETA-CATENIN; STEM-CELLS; TRANSCRIPTIONAL REGULATION; MYELODYSPLASTIC SYNDROMES; MYELOGENOUS LEUKEMIA; DROSOPHILA EMBRYO; OKIHIRO-SYNDROME; SELF-RENEWAL AB SALL4, a human homolog to Drosophila spalt, is a novel zinc finger transcriptional factor essential for development. We cloned SALL4 and its isoforms (SALL4A and SALL4B). Through immunohistochemistry and real-time reverse-transcription-polymerase chain reaction (RT-PCR), we demonstrated that SALL4 was constitutively expressed in human primary acute myeloid leukemia (AML, n = 81), and directly tested the leukemogenic potential of constitutive expression of SALL4 in a murine model. SALL4B transgenic mice developed myelodysplastic syndrome (MDS)-like features and subsequently AML that was transplantable. Increased apoptosis associated with dysmyelopoiesis was evident in transgenic mouse marrow and colony-formation (CFU) assays. Both isoforms could bind to beta-catenin and synergistically enhanced the Wnt/beta-catenin signaling pathway. Our data suggest that the constitutive expression of SALL4 causes MDS/AML, most likely through the Wnt/beta-catenin pathway. Our murine model provides a useful platform to study human MDS/AML transformation, as well as the Wnt/beta-catenin pathway's role in the pathogenesis of leukemia stem cells. C1 Harvard Univ, Sch Med, Dept Pathol,Joint Program Transfus Med, Brigham & Womens Hosp,Childrens Hosp Boston, Boston, MA 02115 USA. Nevada Canc Inst, Div Lab Med, Las Vegas, NV USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. RP Chai, L (reprint author), Harvard Univ, Sch Med, Dept Pathol,Joint Program Transfus Med, Brigham & Womens Hosp,Childrens Hosp Boston, 75 Francis St, Boston, MA 02115 USA. EM yma@nvcancer.org FU NCI NIH HHS [K08 CA 097185]; NCRR NIH HHS [P20 RR 016464]; NIDDK NIH HHS [K08 DK 063220, K08 DK063220] NR 44 TC 111 Z9 138 U1 0 U2 4 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 OCT 15 PY 2006 VL 108 IS 8 BP 2726 EP 2735 DI 10.1182/blood-2006-02-001594 PG 10 WC Hematology SC Hematology GA 092XT UT WOS:000241131700041 PM 16763212 ER PT J AU Chng, WJ Schop, RF Price-Troska, T Ghobrial, I Kay, N Jelinek, DF Gertz, MA Dispenzieri, A Lacy, M Kyle, RA Greipp, PR Tschumper, RC Fonseca, R Bergsagel, PL AF Chng, Wee J. Schop, Roelandt F. Price-Troska, Tammy Ghobrial, Irene Kay, Neil Jelinek, Diane F. Gertz, Morie A. Dispenzieri, Angela Lacy, Martha Kyle, Robert A. Greipp, Philip R. Tschumper, Renee C. Fonseca, Rafael Bergsagel, Peter Leif TI Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma SO BLOOD LA English DT Article ID MEMORY B-CELLS; PLASMA-CELLS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; CHROMOSOMAL-ABNORMALITIES; PERIPHERAL-BLOOD; IGM; LYMPHOMA; ZAP-70; TRANSLOCATIONS AB Waldenstrom macroglobulinemia (WM) is a B-cell malignancy characterized by the ability of the B-cell clone to differentiate into plasma cells. Although the clinical syndrome and the pathologic characteristics are well defined, little is known about its biology and controversy still exists regarding its cell of origin. In this gene-expression study, we compared the transcription profiles of WM with those of other malignant B cells including (chronic lymphocytic leukemia [CLL] and multiple myeloma [MM]) as well as normal cells (peripheral-blood B cells and bone marrow plasma cells). We found that WM has a homogenous gene expression regardless of 6q deletion status and clusters with CLL and normal B cells on unsupervised clustering with very similar expression profiles. Only a small gene set has expression profiles unique to WM compared to CLL and MM. The most significantly up-regulated gene is IL6 and the most significantly associated pathway for this set of genes is MAPK signaling. Thus, IL6 and its downstream signaling may be of biologic importance in WM. Further elucidation of the role of IL-6 in WM is warranted as this may offer a potential therapeutic avenue. C1 Mayo Clin, Dept Hematol Oncol, Scottsdale, AZ USA. Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Div Internal Med, Coll Med, Mayo Grad Sch, Rochester, MN USA. Mayo Clin, Dept Immunol, Coll Med, Mayo Grad Sch, Rochester, MN USA. Mayo Clin, Div Hematol, Coll Med, Mayo Grad Sch, Rochester, MN USA. RP Bergsagel, PL (reprint author), 13208 E Shea Blvd,Suite 300, Scottsdale, AZ 85259 USA. EM fonseca.rafael@mayo.edu RI Bergsagel, Peter/A-7842-2011; OI Bergsagel, Peter/0000-0003-1523-7388; Fonseca, Rafael/0000-0002-5938-3769; Dispenzieri, Angela/0000-0001-8780-9512 FU NCI NIH HHS [CA 95241, P01 CA 62242, P50 CA 200707-01, R01 CA 83724-01] NR 39 TC 97 Z9 98 U1 0 U2 3 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 OCT 15 PY 2006 VL 108 IS 8 BP 2755 EP 2763 DI 10.1182/blood-2006-02-005488 PG 9 WC Hematology SC Hematology GA 092XT UT WOS:000241131700044 PM 16804116 ER PT J AU Shammas, MA Neri, P Koley, H Batchu, RB Bertheau, RC Munshi, V Prabhala, R Fulciniti, M Tai, Y Treon, SP Goyal, RK Anderson, KC Munshi, NC AF Shammas, Masood A. Neri, Paola Koley, Hemanta Batchu, Ramesh B. Bertheau, Robert C. Munshi, Vidit Prabhala, Rao Fulciniti, Mariateresa Tai, Yu tzu Treon, Steven P. Goyal, Raj K. Anderson, Kenneth C. Munshi, Nikhil C. TI Specific killing of multiple myeloma cells by (-)-epigaflocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications SO BLOOD LA English DT Article ID INDUCED ESOPHAGEAL TUMORIGENESIS; CULTURED-MAMMALIAN-CELLS; EPIGALLOCATECHIN GALLATE; GROWTH ARREST; DAP-KINASE; TELOMERASE INHIBITION; CARCINOMA-CELLS; PROTEIN-KINASE; IN-VITRO; APOPTOSIS AB Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin. receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAl-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappa B activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU NIDDK NIH HHS [DK 031092]; PHS HHS [P01 78378, P50 100007] NR 41 TC 90 Z9 97 U1 0 U2 5 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 OCT 15 PY 2006 VL 108 IS 8 BP 2804 EP 2810 DI 10.1182/blood-2006-05-022814 PG 7 WC Hematology SC Hematology GA 092XT UT WOS:000241131700050 PM 16809610 ER PT J AU Krown, SE Niedzwiecki, D Hwu, WJ Hodgson, L Houghton, AN Haluska, FG AF Krown, Susan E. Niedzwiecki, Donna Hwu, Wen-Jen Hodgson, Lydia Houghton, Alan N. Haluska, Frank G. CA Canc Leukemia Grp B TI Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain - High rate of thromboembolic events (CALGB 500102) SO CANCER LA English DT Article DE malignant melanoma; brain metastases; temozolomide; thalidomide; thrombosis ID DEEP-VEIN THROMBOSIS; REFRACTORY MULTIPLE-MYELOMA; BREAST-CANCER PATIENTS; PLUS THALIDOMIDE; PROGNOSTIC-FACTORS; VENOUS THROMBOEMBOLISM; RECEIVING THALIDOMIDE; ARTERIAL THROMBOSIS; ADJUVANT THERAPY; VASCULAR EVENTS AB BACKGROUND. Preliminary studies suggesting that extended-dose temozolomide with thalidomide is safe and active in patients with metastatic melanoma have led to frequent use of this oral regimen. To confirm these observations the combination was tested in a multicenter Phase 11 trial in patients with melanoma brain metastases. METHODS. Eligible patients had melanoma brain metastases, with or without systemic metastases. The primary endpoint was response rate in brain metastases. Patients received temozolomide at a dose of 75 mg/m(2)/day for 6 weeks with a 2-week rest between cycles, and thalidomide (escalated to 400 mg/day for patients age < 70 years or to 200 mg/day for patients age >= 70 years). A 2-stage design required >= 3 responses in the first 21 patients before enrolling 29 additional patients in the second stage. RESULTS. Sixteen eligible patients were enrolled. No objective responses were observed. The median survival was 23.9 weeks. Seven patients withdrew because of tumor progression; 7 were removed during Cycle I because of adverse events, including allergic reaction (I patient), severe fatigue (I patient), sudden death (I patient), and thromboembolic events (pulmonary embolism in 3 patients and deep vein thrombosis in I patient); 2 patients withdrew when the study was suspended and subsequently closed. No associations could be established between baseline characteristics and toxicity. CONCLUSIONS. The proportion of patients with lethal or potentially life-threatening adverse events was high (0.31, 95% confidence interval, 0.11-0.59), and the absence of objective responses made it unlikely that further accrual would demonstrate the efficacy of the regimen. These observations provide little support for the use of this combination for melanoma brain metastases unless safe and effective methods to prevent thrombosis are developed. (c) 2006American Cancer Society. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Krown, SE (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM krowns@mskcc.org FU NCI NIH HHS [CA77651, CA31946, CA33601, CA12449] NR 48 TC 42 Z9 43 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 BP 1883 EP 1890 DI 10.1002/cncr.22239 PG 8 WC Oncology SC Oncology GA 093MB UT WOS:000241171300019 PM 16986123 ER PT J AU Chen, MS Shinagawa, SM Bal, DG Bastani, R Chow, EA Ho, RCS Jones, L McPhee, SJ Senie, R Taylor, V Kagawa-Singer, M Stewart, S Koh, HK Li, FR AF Chen, Moon S., Jr. Shinagawa, Susan M. Bal, Dileep G. Bastani, Roshan Chow, Edward A. Ho, Reginald C. S. Jones, Lovell McPhee, Stephen J. Senie, Ruby Taylor, Vicky Kagawa-Singer, Marjorie Stewart, Susan Koh, Howard K. Li, Frederick R. TI Asian American network for cancer awareness, research, and training's legacy - The first 5 years SO CANCER LA English DT Article DE community health networks; Asian Americans; cancer; training; awareness; research ID NEW-YORK-CITY; HEALTH DISPARITIES; MORTALITY-RATES; CLINICAL-TRIALS; BREAST-CANCER; HEPATITIS-B; AANCART; CALIFORNIA; COMMUNITY; WOMEN AB The Asian American Network for Cancer Awareness, Research, and Training (AANCART) is the first special populations network for Asian Americans on a national basis and includes collaborating organizations from Boston, New York, Houston, Seattle, San Francisco, Los Angeles, Hawaii, and Sacramento (where it is headquartered at the University of California, Davis). NCI funding of AANCART in 2000 brought together investigators and leaders from 9 cities across 6 states to establish an infrastructure for addressing cancer awareness, research, and training. Since 2000, AANCART has conducted needs assessments, held community awareness activities and trainings, trained trainees, sponsored National Asian American Cancer Control Academies, and produced presentations, publications, and grants. All specific aims have been attained, including the establishment of an infrastructure to promote Asian American cancer awareness, research, and training in 4 targeted regions; the establishment of partnerships to promote accrual to clinical trials, training, and pilot studies; and the formulation and successful implementation of grant-funded research to reduce the cancer burden among Asian Americans. AANCART's first 5 years have increased cancer awareness, trained special populations scientists, and advanced the field of Asian American cancer control research. C1 Univ Calif Davis, AANCART, Davis Canc Ctr, Dept Publ Hlth Sci, Sacramento, CA 95817 USA. AANCART, San Diego, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv Res, Los Angeles, CA 90024 USA. Chinese Community Hlth Care Assoc, San Francisco, CA USA. Chinese Community Hlth Plan, San Francisco, CA USA. Straub Clin & Hosp, Dept Oncol, Honolulu, HI USA. Univ Texas, MD Anderson Canc Ctr, Ctr Res Minor Hlth, Houston, TX 77030 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. Columbia Univ, Dept Publ Hlth, New York, NY USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Publ Hlth & Asian Amer Studies, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Chen, MS (reprint author), Univ Calif Davis, AANCART, Davis Canc Ctr, Dept Publ Hlth Sci, Suite 3010,4501 X St, Sacramento, CA 95817 USA. EM moon.chen@ucdmc.ucdavis.edu FU NCI NIH HHS [U01-CA86322-05] NR 53 TC 5 Z9 5 U1 3 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 SU S BP 2006 EP 2014 DI 10.1002/cncr.22160 PG 9 WC Oncology SC Oncology GA 095DX UT WOS:000241289500012 PM 16977597 ER PT J AU Goldstein, AM Chan, M Harland, M Gillanders, EM Hayward, NK Avril, MF Azizi, E Bianchi-Scarra, G Bishop, DT Bressac-de Paillerets, B Bruno, W Calista, D Albright, LAC Demenais, F Elder, DE Ghiorzo, P Gruis, NA Hansson, J Hogg, D Holland, EA Kanetsky, PA Kefford, RF Landi, MT Lang, J Leachman, SA MacKie, RM Magnusson, V Mann, GJ Niendorf, K Bishop, JN Palmer, JM Puig, S Puig-Butille, JA de Snoo, FA Stark, M Tsao, H Tucker, MA Whitaker, L Yakobson, E AF Goldstein, Alisa M. Chan, May Harland, Mark Gillanders, Elizabeth M. Hayward, Nicholas K. Avril, Marie-Francoise Azizi, Esther Bianchi-Scarra, Giovanna Bishop, D. Timothy Bressac-de Paillerets, Brigitte Bruno, William Calista, Donato Cannon Albright, Lisa A. Demenais, Florence Elder, David E. Ghiorzo, Paola Gruis, Nelleke A. Hansson, Johan Hogg, David Holland, Elizabeth A. Kanetsky, Peter A. Kefford, Richard F. Landi, Maria Teresa Lang, Julie Leachman, Sancy A. MacKie, Rona M. Magnusson, Veronica Mann, Graham J. Niendorf, Kristin Newton Bishop, Julia Palmer, Jane M. Puig, Susana Puig-Butille, Joan A. de Snoo, Femke A. Stark, Mitchell Tsao, Hensin Tucker, Margaret A. Whitaker, Linda Yakobson, Emanuel CA Lund Melanoma Stdy Grp Melanoma Genetics Consortium GenoM TI High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL SO CANCER RESEARCH LA English DT Article ID MULTIPLE PRIMARY MELANOMAS; POPULATION-BASED SAMPLE; FAMILIAL MELANOMA; GERMLINE MUTATIONS; CDKN2A MUTATIONS; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; PRONE FAMILIES; CDK4 MUTATION; P16 AB GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, cdVS2-105A > G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Inherited Dis Res Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Canc Res UK Clin Ctr, Genet Epidemiol Div, Leeds, W Yorkshire, England. Univ Glasgow, Dept Med Genet, Glasgow, Lanark, Scotland. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW 2006, Australia. Inst Gustave Roussy, Serv Dermatol, F-94805 Villejuif, France. Inst Gustave Roussy, Serv Genet, F-94805 Villejuif, France. Univ Evry, INSERM, U794, Evry, France. Tel Aviv Univ, Sackler Fac Med, Chaim Sheba Med Ctr, Dept Internal Med C,Mol Cell Biol Lab, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Dept Dermatol, IL-69978 Tel Aviv, Israel. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy. Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. Karolinska Univ Hosp Solna, Stockholm, Sweden. Univ Hosp, Lund Canc Ctr, Dept Oncol, Lund, Sweden. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Barcelona, Dept Dermatol, Barcelona, Spain. Univ Barcelona, Genet Serv, Melanoma Unit,Hosp Clin, Inst Invest Biomed August Pi Surie, Barcelona, Spain. RP Goldstein, AM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Execut Plaza S,Room 7004,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. EM goldstea@exchange.nih.gov RI Stark, Mitchell/E-3542-2010; Hoiom, Veronica/F-4153-2012; Mann, Graham/G-4758-2014; Bianchi Scarra, Giovanna/G-8933-2014; Demenais, Florence/G-3298-2013; Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; Whiteman, David/P-2728-2014; Bruno, William/N-7477-2013; OI Stark, Mitchell/0000-0002-4510-2161; Mann, Graham/0000-0003-1301-405X; Gruis, Nelleke/0000-0002-5210-9150; Bianchi Scarra, Giovanna/0000-0002-6127-1192; Demenais, Florence/0000-0001-8361-0936; hayward, nicholas/0000-0003-4760-1033; Whiteman, David/0000-0003-2563-9559; Bruno, William/0000-0002-0337-0168; Bishop, Tim/0000-0002-8752-8785; albright, lisa/0000-0003-2602-3668; Puig, Susana/0000-0003-1337-9745; Martin, Nicholas/0000-0003-4069-8020 FU Intramural NIH HHS; NCI NIH HHS [N01-PC-35141, 1 R01 CA83115-01A2, R01 CA 88363, R01 CA102422] NR 60 TC 200 Z9 200 U1 1 U2 14 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 OCT 15 PY 2006 VL 66 IS 20 BP 9818 EP 9828 DI 10.1158/0008-5472.CAN-06-0494 PG 11 WC Oncology SC Oncology GA 096QU UT WOS:000241392700007 PM 17047042 ER PT J AU Kuroda, T Rabkin, SD Martuza, RL AF Kuroda, Toshihiko Rabkin, Samuel D. Martuza, Robert L. TI Effective treatment of tumors with strong beta-catenin T-cell factor activity by transcriptionally targeted oncolytic herpes simplex virus vector SO CANCER RESEARCH LA English DT Article ID COLON-CANCER CELLS; WNT SIGNALING PATHWAY; SOMATIC MUTATIONS; COLORECTAL-CANCER; MALIGNANT GLIOMAS; GENE; APC; ACTIVATION; EXPRESSION; PROMOTER AB The Wnt/beta-catenin/T-cell factor (Tcf) pathway is aberrantly up-regulated in the majority of colorectal cancers (CRC) and hepatoblastomas due to either an APC or beta-catenin gene mutation. We constructed synthetic promoters, T and TE, which contain tandem repeats of a Tcf responsive element without and with the human 4172 gene intronic enhancer, respectively. Although the T and TE promoters showed higher transcriptional activity than a control promoter in all CRC and hepatoblastoma cell lines tested, with low activities in most other tumor cell lines, the level of transcription varied considerably among the CRC and hepatoblastoma cell lines. In some CRC cell lines, the TE promoter displayed higher levels of transcription than even the human CMVIE promoter. In those CRC cells, the APC gene mutations were located within a small segment between the first and second 20-amino-acid repeats in the mutation cluster region of the APC protein. We created a transcriptionally targeted oncolytic herpes simplex virus vector (bM24-TE) in which replication is driven by the TE promoter. This vector efficiently and specifically replicated in and killed tumor cells with strong beta-catenin/Tcf signaling. Intratumoral injection of bM24-TE significantly reduced the growth of highly beta-catenin active SW480 CRC tumors and induced a complete response in half of them, whereas it had no effect on the growth of beta-catenin-inactive A549 tumors. Our results suggest that a transcriptionally regulated oncolytic herpes vector targeting beta-catenin/Tcf signal is very efficacious against CRC tumors carrying an APC gene mutation between the first and second 20-amino-acid repeats. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Mol Neurosurg Lab, Boston, MA 02114 USA. RP Kuroda, T (reprint author), 185 Cambridge St,CPZN-3800, Boston, MA 02114 USA. EM kuroda@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012; OI rabkin, samuel/0000-0003-2344-2795; Kuroda, Toshihiko/0000-0001-6660-8930 FU NCI NIH HHS [R01 CA102139]; NINDS NIH HHS [R01 NS032677] NR 43 TC 30 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2006 VL 66 IS 20 BP 10127 EP 10135 DI 10.1158/0008-5472.CAN-06-2744 PG 9 WC Oncology SC Oncology GA 096QU UT WOS:000241392700042 PM 17047077 ER PT J AU Hur, J Bell, DW Dean, KL Coser, KR Hilario, PC Okimoto, RA Tobey, EM Smith, SL Isselbacher, KJ Shioda, T AF Hur, Jingyung Bell, Daphne W. Dean, Kathleen L. Coser, Kathryn R. Hilario, Pablo C. Okimoto, Ross A. Tobey, Erica M. Smith, Shannon L. Isselbacher, Kurt J. Shioda, Toshi TI Regulation of expression of BIK proapoptotic protein in human breast cancer cells: p53-dependent induction of BIK mRNA by fulvestrant and proteasomal degradation of BIK protein SO CANCER RESEARCH LA English DT Article ID MITOCHONDRIAL APOPTOSIS; INHIBITOR BORTEZOMIB; BH3-ONLY PROTEINS; GENE-EXPRESSION; ANNEXIN-V; ESTROGEN; PATHWAYS; DEATH; PROLIFERATION; ANTIESTROGEN AB Induction of mRNA for BIK proapoptotic protein by doxorubicin or gamma-irradiation requires the DNA-binding transcription factor activity of p53. In MCF7 cells, pure antiestrogen fulvestrant also induces BIK mRNA and apoptosis. Here, we provide evidence that, in contrast to doxorubicin or gamma-irradiation, fulvestrant induction of BIK mRNA is not a direct effect of the transcriptional activity of p53, although p53 is necessary for this induction. It is known that p53 up-regulated modulator of apoptosis (PUMA) mRNA is induced directly by the transcriptional activity of p53. Whereas gamma-irradiation induced both BIK and PUMA mRNA, only BIK mRNA was induced by fulvestrant. Whereas both fulvestrant and doxorubicin induced BIK mRNA, only doxorubicin enhanced the DNA-binding activity of p53 and induced PUMA mRNA. Small interfering RNA (siRNA) suppression of p53 expression as well as overexpression of dominant-negative p53 effectively inhibited the fulvestrant induction of BIK mRNA, protein, and apoptosis. Transcriptional activity of a 2-kb BIK promoter, which contained an incomplete p53-binding sequence, was not affected by fulvestrant when tested by reporter assay. Fulvestrant neither affected the stability of the BIK mRNA transcripts. Interestingly, other human breast cancer cells, such as ZR75-1, constitutively expressed BIK mRNA even without fulvestrant. In these cells, however, BIK protein seemed to be rapidly degraded by proteasome, and siRNA suppression of BIK in ZR75-1 cells inhibited apoptosis induced by MG132 proteasome inhibitor. These results suggest that expression of BIK in human breast cancer cells is regulated at the mRNA level by a mechanism involving a nontranscriptional activity of p53 and by proteasomal degradation of BIK protein. C1 Massachusetts Gen Hosp, Canc Res Ctr, Dept Tumor Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Canc Res Ctr, Mol Profiling Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Canc Res Ctr, Ctr Canc Risk Anal, Charlestown, MA 02129 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, Dept Tumor Biol, Bldg 149,7th Floor,13th St, Charlestown, MA 02129 USA. EM tshioda@partners.org NR 50 TC 33 Z9 33 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2006 VL 66 IS 20 BP 10153 EP 10161 DI 10.1158/0008-5472.CAN-05-3696 PG 9 WC Oncology SC Oncology GA 096QU UT WOS:000241392700045 PM 17047080 ER PT J AU Mao, J Ligon, KL Rakhlin, EY Thayer, SP Bronson, RT Rowitch, D McMahon, AP AF Mao, Junhao Ligon, Keith L. Rakhlin, Elena Y. Thayer, Sarah P. Bronson, Roderick T. Rowitch, David McMahon, Andrew P. TI A novel somatic mouse model to survey tumorigenic potential applied to the hedgehog pathway SO CANCER RESEARCH LA English DT Article ID BASAL-CELL CARCINOMA; SONIC-HEDGEHOG; MEDULLOBLASTOMA FORMATION; SIGNALING PATHWAY; PROSTATE-CANCER; LUNG-CANCER; GLI PATHWAY; MICE; GROWTH; GENE AB We report a novel mouse model for the generation of sporadic tumors and show the efficiency of this approach by surveying Hedgehog (Hh)-related tumors. Up-regulation of the Hh pathway is achieved by conditionally regulated expression of an activated allele of Smoothened (R26-SmoM2) using either sporadic leakage or global postnatal induction of a ubiquitously expressed inducible Cre transgene (CAGGS-CreER). Following postnatal tamoxifen induction, CAGGS-CreER, R26-SmoM2 mice developed tumors with short latency and high penetrance. All mice exhibited rhabdomyosarcoma and basal cell carcinoma; 40% also developed medulloblastoma. In addition, mice showed a novel pancreatic lesion resembling low-grade mucinous cystic neoplasms in humans. In contrast, widespread activation of SmoM2 in the postnatal prostate epithelium results in no detectable morphologic outcome in 12-month-old mice. Comparison of gene expression profiles among diverse tumors identified several signature genes, including components of platelet-derived growth factor and insulin-like growth factor pathways, which may provide a common mechanistic link to the Hh-related malignancies. This experimental model provides a robust tool for exploring the process of Hh-dependent tumorigenesis and the treatment of such tumors. More generally, this approach provides a genetic platform for identifying tumorigenic potential in putative oncogenes and tumor suppressors and for more effective modeling of sporadic cancers in mice. C1 Harvard Univ, Biol Labs, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA USA. RP McMahon, AP (reprint author), Harvard Univ, Biol Labs, Dept Mol & Cellular Biol, Room 1059,16 Divin Ave, Cambridge, MA 02138 USA. EM mcmahon@mcb.harvard.edu FU NIDDK NIH HHS [K08 DK071329]; NINDS NIH HHS [R37 NS033642, R37-NS033642] NR 50 TC 135 Z9 138 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2006 VL 66 IS 20 BP 10171 EP 10178 DI 10.1158/0008-5472.CAN-06-0657 PG 8 WC Oncology SC Oncology GA 096QU UT WOS:000241392700047 PM 17047082 ER PT J AU Giaccone, G Ruiz, MG Le Chevalier, T Thatcher, N Smit, E Rodriguez, JA Janne, P Oulid-Aissa, D Soria, JC AF Giaccone, Giuseppe Ruiz, Marielle Gallegos Le Chevalier, Thierry Thatcher, Nick Smit, Egbert Rodriguez, Jose Antonio Janne, Pasi Oulid-Aissa, Dalila Soria, Jean-Charles TI Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; EGFR MUTATIONS; GENE-MUTATIONS; SINGLE-AGENT; GEFITINIB; COMBINATION; TRIAL; INHIBITORS; CHEMOTHERAPY AB Purpose: Erlotinib has proven activity in pretreated patients with advanced non-small cell lung cancer (NSCLC). We evaluated erlotinib in the frontline treatment of advanced NSCLC and assessed biological predictors of outcome. Experimental Design: In this phase II study, chemotherapy-naive patients with stage IIIB/IV NSCLC received oral erlotinib (150 mg/d) until disease progression or unacceptable toxicity occurred. Tumor response was assessed every 6 weeks, and samples were analyzed' for potential molecular markers of treatment response and survival. The primary end point was the proportion of patients without disease progression after 6 weeks of treatment. Results: Fifty-three patients were eligible. The overall rate of nonprogression at 6 weeks was 52.8% (28 of 53 patients). Tumor response rate was 22.7%, with 1 complete response, 11 partial responses, and 16 cases of stable disease. Responses were seen across most patient clinical characteristics. The median duration of tumor response was 333 days; median overall survival was 391 days; and median time to disease progression was 84 days. Erlotinib was well tolerated, the main treatment-related adverse events being mild-to-moderate rash and diarrhea. Histologic material for biological studies was available in 29 cases. Four of five responders and one patient with stable disease had a classic epidermal growth factor receptor tyrosine kinase mutation. Two progressing patients exhibited epidermal growth factor receptor point mutations (one with T790 M mutation), and K-ras mutations were detected in 10 nonresponders. Conclusions: Erlotinib shows significant antitumor activity in the first-line treatment of advanced NSCLC and may be a viable alternative to chemotherapy. Patient selection cannot easily be based on clinical or biological variables. C1 Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Pulm Dis, NL-1081 HV Amsterdam, Netherlands. Inst Gustave Roussy, Paris, France. Christie Hosp Manchester NHS Trust, Manchester, Lancs, England. Dana Farber Canc Ctr, Boston, MA USA. Hoffmann La Roche Ltd, Basel, Switzerland. RP Giaccone, G (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM g.giaccone@vumc.nl RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 41 TC 135 Z9 148 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2006 VL 12 IS 20 BP 6049 EP 6055 DI 10.1158/1078-0432.CCR-06-0260 PN 1 PG 7 WC Oncology SC Oncology GA 097SH UT WOS:000241468300022 PM 17062680 ER PT J AU Lipton, A Berenson, JR Body, JJ Boyce, BF Bruland, OS Carducci, MA Cleeland, CS Clohisy, DR Coleman, RE Cook, RJ Guise, TA Pearse, RN Powles, TJ Rogers, MJ Roodman, GD Smith, MR Suva, LJ Vessella, RL Weilbaecher, KN Kingc, L AF Lipton, Allan Berenson, James R. Body, Jean-Jacques Boyce, Brendan F. Bruland, Oyvind S. Carducci, Michael A. Cleeland, Charles S. Clohisy, Denis R. Coleman, Robert E. Cook, Richard J. Guise, Theresa A. Pearse, Roger N. Powles, Trevor J. Rogers, Michael J. Roodman, G. David Smith, Matthew R. Suva, Larry J. Vessella, Robert L. Weilbaecher, Katherine N. King, Laura TI Advances in treating metastatic bone cancer: Summary statement for the First Cambridge Conference SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT Conference on Advances in Treating Metastatic Bone Cancer CY OCT 28-29, 2005 CL Cambridge, MA ID ANDROGEN-DEPRIVATION THERAPY; HORMONE-RELATED PROTEIN; BREAST-CANCER; TGF-BETA; OSTEOPOROSIS; PROSTATE; PATHOGENESIS; OSTEOLYSIS; CARCINOMA; DIAGNOSIS AB The First Cambridge Conference on Advances in Treating Metastatic Bone Cancer, a symposium held in Cambridge, Massachusetts, October 28 to 29, 2005, was convened to discuss recent advances and research related to the natural history of bone metastases and skeletal complications, bone cancer biology, treatment of myeloma and other solid tumors, and treatment-induced bone loss. The conference format combined brief presentations with extended periods of discussion. The conclusions reached during the 2-day meeting are summarized in this article and presented in more detail in the individual articles and accompanying discussion sessions that comprise the conference proceedings. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. Univ Libre Bruxelles, CHU Brugmann, Brussels, Belgium. Univ Libre Bruxelles, Inst Jules Bordet, Dept Internal Med, Brussels, Belgium. Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY USA. Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. Univ Minnesota, Ctr Canc, Dept Orthoped Surg, Minneapolis, MN USA. Weston Pk Hosp, Ctr Canc Res, Acad Unit Clin Oncol, Sheffield, S Yorkshire, England. Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. Univ Virginia, Dept Endocrinol & Med, Charlottesville, VA USA. Cornell Univ, Coll Med, Dept Med, Div Hematol Oncol, New York, NY USA. Parkside Oncol Ctr, London, England. Univ Aberdeen, Inst Med Sci, Bone Res Grp, Aberdeen, Scotland. Univ Pittsburgh, Pittsburgh, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol,Canc Ctr, Boston, MA USA. Univ Arkansas Med Sci, Ctr Orthopaed Res, Little Rock, AR 72205 USA. Univ Washington, Sch Med, Genitourinary Canc Res Lab, Seattle, WA USA. Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. Informed Commun Inc, Carlisle, MA USA. RP Lipton, A (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, 500 Univ Dr,H046,POB 850, Hershey, PA 17033 USA. EM alipton@psu.edu FU NCI NIH HHS [P01 CA100730, P01 CA100730-010005, R01 CA097250, R01 CA097250-01A1] NR 24 TC 12 Z9 13 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2006 VL 12 IS 20 SU S BP 6209S EP 6212S DI 10.1158/1078-0432.CCR-06-1213 PN 2 PG 4 WC Oncology SC Oncology GA 099AC UT WOS:000241563900001 PM 17062702 ER PT J AU Roodman, GD AF Roodman, G. David TI New potential targets for treating myeloma bone disease SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT Conference on Advances in Treating Metastatic Bone Cancer CY OCT 28-29, 2005 CL Cambridge, MA ID INFLAMMATORY PROTEIN-1 ALPHA; MULTIPLE-MYELOMA; OSTEOLYTIC LESIONS; CELLS; EXPRESSION; DIFFERENTIATION; DESTRUCTION; INHIBITION; 1-ALPHA; MODEL AB Purpose: Myeloma bone disease results, in severe pain and pathologic fractures in >80% of patients. Myeloma bone disease is characterized, by both increased osteoclast activity and suppressed new bone formation. The basis for both, the increased bone destruction and decreased bone formation has been a topic of extensive investigation during the last several years. Experimental Design: Marrow samples for patients with myeloma were screened by both molecular biological and gene expression profiling techniques to identify factors that may be responsible for the enhanced bone destruction and suppressed bone formation in patients with the disease. Results: Several novel factors have been identified that directly stimulate osteoclastic bone destruction in myeloma. These include receptor activation NF-kappa B ligand, macrophage inflammatory peptide 1 alpha and interleukin (IL)-3. All of these factors are increased in most patients with myeloma. Furthermore osteoprotegerin levels are markedly suppressed, further driving osteoclast formation. In addition, four novel inhibitors of osteoblast differentiation or activity have been identified. These include two inhibitors of the Wnt signaling pathway. DKK1 and soluble frizzled protein 2. The Wnt signaling pathway is critical for osteoblast differentiation. Two cytokines IL-3 and IL-7, have also been reported that directly or indirectly inhibit osteoblast differentiation in patients with myeloma. Interestingly, increased macrophage inflammatory peptide 1 alpha, IL-3 and IL-7 result from abnormal transcriptional regulation of these genes by increased levels of acute myelogenous leukemia-1 to acute myelogenous leukemia-1B transcription factors. Conclusions: The recent identification of novel stimulators of osteoclast activity and inhibitors of osteoblast differentiation provide new therapeutic targets for treating this devastating bone disease in patients with myeloma. C1 VA Pittsburgh Healthcare Syst, R&D, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med Hematol Oncol, Pittsburgh, PA USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, R&D, 151-U,Room 2E-113,Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 25 TC 14 Z9 17 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 OCT 15 PY 2006 VL 12 IS 20 SU S BP 6270S EP 6273S DI 10.1158/1078-0432.CCR-06-0845 PN 2 PG 4 WC Oncology SC Oncology GA 099AC UT WOS:000241563900011 PM 17062712 ER PT J AU Smith, MR AF Smith, Matthew R. TI Treatment-related osteoporosis in men with prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT Conference on Advances in Treating Metastatic Bone Cancer CY OCT 28-29, 2005 CL Cambridge, MA ID BONE-MINERAL DENSITY; ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; VITAMIN-D; POSTMENOPAUSAL WOMEN; HORMONE AGONISTS; BODY-COMPOSITION; FRACTURE RISK; SEX STEROIDS; OLDER MEN AB The intended therapeutic effect of gonadotropin-releasing hormone (GnRH) agonists is hypogonadism, a major cause of acquired osteoporosis in men. Consistent with this observation, GnRH agonists increase bone turnover and decrease bone mineral density a surrogate for fracture risk. Large claims-based analyses and other retrospective studies provide compelling evidence the GnRH agonists increase risk of clinical fractures. Estrogens play a central role in homeostasis of the normal male skeleton, and estrogen deficiency rather than testosterone deficiency seems to be primarily responsible for the adverse skeletal effects of GnRH agonists. In randomized controlled trials, bisphosphonates (pamidronate and zoledronic acid) and selective estrogen receptor modulators (raloxifene and toremifene) increased bone mineral density in GnRH agonist - treated men. Two ongoing large randomized placebo-controlled studies will prospectively define fracture outcomes in men with prostate cancer and assess the efficacy of novel pharmacologic interventions (AMG162 toremifene) during GnRH agonist treatment. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [K24 CA121990, K24 CA121990-01A1] NR 50 TC 35 Z9 35 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 OCT 15 PY 2006 VL 12 IS 20 SU S BP 6315S EP 6319S DI 10.1158/1078-0432.CCR-06-0846 PN 2 PG 5 WC Oncology SC Oncology GA 099AC UT WOS:000241563900020 PM 17062721 ER PT J AU Musher, DM Rueda-Jaimes, AM Graviss, EA Rodriguez-Barradas, MC AF Musher, Daniel M. Rueda-Jaimes, Adriana M. Graviss, Edward A. Rodriguez-Barradas, Maria C. TI Effect of pneumococcal vaccination: A comparison of vaccination rates in patients with bacteremic and nonbacteremic pneumococcal pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYSACCHARIDE VACCINE; STREPTOCOCCUS-PNEUMONIAE; EFFICACY; DISEASE; ADULTS AB Background. Despite the widespread acceptance of the 23-valent pneumococcal capsular polysaccharide vaccine (PPV), its protective effect continues to be disputed. We describe a novel approach to examine the protective effect of this vaccine. Methods. We recorded the vaccination status of every patient for whom a culture yielded Streptococcus pneumoniae during a 4.5-year period, comparing rates of prior PPV administration in patients with ( 1) bacteremic pneumococcal pneumonia, ( 2) all-invasive pneumococcal disease, ( 3) nonbacteremic pneumococcal pneumonia, ( 4) acute exacerbation of chronic bronchitis (AECB) due to S. pneumoniae, and ( 5) pneumococcal colonization. The principal comparisons were with patients who had bacteremic pneumonia or any invasive pneumococcal disease and those with nonbacteremic pneumococcal pneumonia. We also compared vaccination rates in patients who had nonbacteremic pneumonia with vaccination rates in patients with AECB or pneumococcal colonization. Results. The rate of prior PPV vaccination was lower among patients with bacteremic pneumococcal pneumonia (39.7%) or any invasive pneumococcal disease (38.0%) than among patients with nonbacteremic pneumonia (57.6%), AECB (60.0%), or pneumococcal colonization (57.8%). PPV conferred a 54% protection rate against bacteremic versus nonbacteremic pneumococcal pneumonia. There was no apparent protection against nonbacteremic pneumonia compared, for example, with colonized persons or with those who had AECB. Conclusions. PPV provides moderate protection against invasive pneumococcal disease but does not protect against nonbacteremic pneumococcal pneumonia. These findings suggest the importance of a continued search for a better pneumococcal vaccine. C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Rm 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM daniel.musher@med.va.gov NR 19 TC 33 Z9 33 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2006 VL 43 IS 8 BP 1004 EP 1008 DI 10.1086/507699 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 086IE UT WOS:000240666200009 PM 16983612 ER PT J AU Anaissie, EJ Segal, BH Graybill, JR Arndt, C Perfect, JR Kleinberg, M Pappas, P Benjamin, D Rubin, R Aberg, JA Adderson, EE Adler-Shohet, FC Akan, H Akova, M Almyroudis, NG Alexander, BD Andes, D Arrieta, A Baddley, JW Barron, MA Belzberg, H Boucher, HW Boyce, TG Casadevall, A Chandrasekar, PH Cleary, JD Cordonnier, C Cornely, OA Cuenca-Estrella, M Daly, JS Daoura, N Denning, DW dePauw, B de Repentigny, L Dignani, MC Dismukes, WE Donnelly, JP Donowitz, GR Dupont, B Drusano, G Ellis, M Espinel-Ingroff, A Fishman, JA Fleming, R Forrest, G Ghannoum, M Goldman, M Grazziutti, M Greene, JN Greenberg, RN Gubbins, PO Hadley, S Herbrecht, R Hiemenz, JW Hope, W Hospenthal, DR Husain, S Ito, JI Jacobson, RM Johnson, M Keating, MR Kett, DH Knapp, K Kontoyiannis, DP Krcmery, VC Larsen, R Laverdiere, M Ljungman, P Lortholary, O Maertens, J Marriott, D Mattiuzzi, G McGinnis, MR Morris, M Nucci, M Odds, FC Pankey, GA Patterson, T Pfaller, M Razonable, RR Reboli, AC Rinaldi, MG Roberts, GD Tudela, JL Rotstein, C Ruhnke, M Schuster, M Shoham, S Sia, IG Siebel, N Silviera, F Singh, N Sobel, J Solomkin, JS Sorrell, TC Steinbach, WJ Temesgen, Z Tortorano, A Vartivarian, S VerWeij, P Viscoli, C Viviani, MA Walker, RC Wheat, JL Wiley, J Williamson, P Wingard, JR Yu, VL Zaoutis, T AF Anaissie, Elias J. Segal, Brahm H. Graybill, John R. Arndt, Carola Perfect, John R. Kleinberg, Michael Pappas, Peter Benjamin, Danny Rubin, Robert Aberg, Judith A. Adderson, Elisabeth E. Adler-Shohet, Felice C. Akan, Hamdi Akova, Murat Almyroudis, Nikolaos G. Alexander, Barbara D. Andes, David Arrieta, Antonio Baddley, John W. Barron, Michelle A. Belzberg, Howard Boucher, Helen W. Boyce, Thomas G. Casadevall, Arturo Chandrasekar, P. H. Cleary, John D. Cordonnier, Catherine Cornely, Oliver A. Cuenca-Estrella, Manuel Daly, Jennifer S. Daoura, Nicholas Denning, David W. dePauw, Ben de Repentigny, Louis Dignani, Maria Cecilia Dismukes, William E. Donnelly, J. Peter Donowitz, Gerald R. Dupont, Bertrand Drusano, George Ellis, Michael Espinel-Ingroff, Ana Fishman, Jay A. Fleming, Rhonda Forrest, Graeme Ghannoum, Mahmoud Goldman, Mitchell Grazziutti, Monica Greene, John N. Greenberg, Richard N. Gubbins, Paul O. Hadley, Susan Herbrecht, Raoul Hiemenz, John W. Hope, William Hospenthal, Durane R. Husain, Shahid Ito, James I. Jacobson, Robert M. Johnson, Melissa Keating, Michael R. Kett, Daniel H. Knapp, Katherine Kontoyiannis, Dimitrios P. Krcmery, Vladimir C. Larsen, Robert Laverdiere, Michel Ljungman, Per Lortholary, O. Maertens, Johan Marriott, Debbie Mattiuzzi, Gloria McGinnis, Michael R. Morris, Michele Nucci, Marcio Odds, Frank C. Pankey, George A. Patterson, Thomas Pfaller, Mike Razonable, Raymond R. Reboli, Annette C. Rinaldi, Michael G. Roberts, Glenn D. Rodriguez Tudela, Juan Luis Rotstein, Coleman Ruhnke, Markus Schuster, Mindy Shoham, Shmuel Sia, Irene G. Siebel, Nita Silviera, Fernanda Singh, Nina Sobel, Jack Solomkin, Joseph S. Sorrell, Tania C. Steinbach, William J. Temesgen, Zelalem Tortorano, AnnaMaria Vartivarian, Shahe VerWeij, Paul Viscoli, Claudio Viviani, Maria Anna Walker, Randall C. Wheat, Joseph L. Wiley, Joseph Williamson, Peter Wingard, John R. Yu, Victor L. Zaoutis, Theoklis TI Clinical research in the lay press: Irresponsible journalism raises a huge dose of doubt SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID LIPOSOMAL AMPHOTERICIN-B; EMPIRICAL ANTIFUNGAL THERAPY; ACUTE-RENAL-FAILURE; INVASIVE ASPERGILLOSIS; NEUTROPENIC PATIENTS; PERSISTENT FEVER; DOUBLE-BLIND; CASPOFUNGIN; CANCER; SAFETY C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharm Practice, Little Rock, AR 72205 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. Metropolitan Infect Dis, Houston, TX USA. Texas Tech Univ, Hlth Sci Ctr, Div Infect Dis, El Paso, TX USA. Univ Texas, Dept Pathol, Galveston, TX 77555 USA. Univ Texas, Dept Dermatol, Galveston, TX 77555 USA. Univ Texas, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Childrens Hosp Sinai, Div Pediat Hematol Oncol, Dept Pediat, Baltimore, MD USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. Univ Pittsburgh, Div Infect Dis, Dept Med, Pittsburgh, PA USA. Childrens Hosp Philadelphia, Dept Pediat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. Ochsner Clin Fdn, New Orleans, LA USA. Louisiana State Univ, Feist Weiller Canc Ctr, Hlth Sci Ctr, Shreveport, LA 71105 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med Genet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Microbiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA. Duke Univ, Med Ctr, Clin Mycol Lab, Durham, NC 27710 USA. Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Tufts Univ, Sch Med, Div Geog Med, Tufts New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Div Infect Dis, Tufts New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Crit Care Serv, Los Angeles, CA USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Childrens Hosp Orange Cty, Los Angeles, CA USA. Miller Childrens Hosp, Long Beach, CA USA. City Hope Natl Med Ctr, Dept Infect Dis, Duarte, CA 91010 USA. Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA USA. Univ Florida, Coll Med, Dept Infect Dis, H Lee Moffitt Canc Ctr, Tampa, FL USA. Jackson Mem Hosp, Med Intens Care Unite, Miami, FL 33136 USA. Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33152 USA. Mayo Clin, Coll Med, Div Infect Dis, Dept Med, Jacksonville, FL 32224 USA. Univ Florida, Coll Med, Dept Med, Div Hematol Oncol, Gainesville, FL USA. Indiana Univ, Sch Med, Dept Med, Immunocompromised Infect Dis Serv, Indianapolis, IN 46204 USA. MiraVista Diagnost MiraBella Technol, Indianapolis, IN USA. Univ Colorado, Dept Med, Div Infect Dis, Denver, CO 80202 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Microbiol, Madison, WI USA. Univ Virginia, Hlth Syst, Dept Med, Charlottesville, VA USA. Virginia Commonwealth Univ, Med Ctr, Dept Med, Richmond, VA USA. Mayo Clin, Div Clin Microbiol, Rochester, NY USA. Mayo Clin, Dept Pediat, Rochester, NY USA. Mayo Clin, Dept Med, Div Infect Dis, Rochester, NY USA. Mayo Clin, Coll Med, Dept Med, Div Infect Dis, Buffalo, NY USA. Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. NYU, Sch Med, New York, NY USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USA. Roswell Pk Canc Ctr, Div Infect Dis, Buffalo, NY USA. Albany Med Coll, Div Clin Pharmacol, Albany, NY USA. Univ Mississippi, Med Ctr, Sch Pharm, Dept Pharm Practice, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Mycot Res Ctr, Dept Med,Div Infect Dis, Jackson, MS 39216 USA. Univ Kentucky, Sch Med, Div Infect Dis, Dept Internal Med, Lexington, KY 40536 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Georgetown Univ, Sch Med, Dept Med, Washington, DC USA. George Washington Univ, Sch Med & Publ Hlth, Dept Pediat, Washington, DC USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Case Western Reserve Univ, Sch Med, Dept Dermatol, Cleveland, OH 44106 USA. Univ Cincinnati, Div Trauma & Crit Care, Dept Surg, Cincinnati, OH USA. Wayne State Univ, Div Infect Dis, Detroit, MI USA. Cooper Univ Hosp, Robert Wood Johnson Med Sch, Dept Med, Div Infect Dis, Camden, NJ USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Aberdeen, Dept Mycol, Aberdeen AB9 1FX, Scotland. Wythenshawe Hosp, Dept Med, Educ Res Ctr, Manchester M23 9LT, Lancs, England. Wythenshawe Hosp, Dept Med Mycol, Educ Res Ctr, Manchester M23 9LT, Lancs, England. Catholic Univ Louvain, Dept Clin Haematol, B-3000 Louvain, Belgium. Univ Nijmegen Hosp, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen Hosp, Dept Hematol, NL-6500 HB Nijmegen, Netherlands. Radboud Univ Nijmegen Med Ctr, Dept Haematol, Nijmegen, Netherlands. Univ Nijmegen, Ctr Infect Dis, Nijmegen, Netherlands. Karolinska Inst, Dept Med, Stockholm, Sweden. Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden. Hosp Maisonneuve Rosemont, Dept Microbiol Infect Dis, Montreal, PQ, Canada. Univ Montreal, Hop St Justine, Dept Microbiol & Immunol, Montreal, PQ H3T 1C5, Canada. McMaster Univ, Div Infect Dis, Hamilton, ON, Canada. Hamilton Hlth Serv, Infect Dis Serv, Hamilton, ON, Canada. Hop Necker Enfants Malad, Serv Malad Infect & Trop, Paris, France. CHU Henri Mondor, Dept Hematol, F-94010 Creteil, France. Hop Hautepierre, Dept Hematol & Oncol, Strasbourg, France. Univ Fed Rio de Janeiro, Univ Hosp, Rio De Janeiro, Brazil. Univ Cologne, Dept Internal Med, Cologne, Germany. Charite Univ Med, Med Klin & Poliklin 2, Berlin, Germany. Fdn Fight Against Leukemia, Dept Infect Dis, Buenos Aires, DF, Argentina. Univ Milan, Dept Publ Hlth Microbiol & Virol, Milan, Italy. Univ Genoa, Div Infect Dis, San Martino Univ Hosp, Genoa, Italy. Ankara Univ, Dept Hematol, TR-06100 Ankara, Turkey. Ankara Univ, Bone Marrow Transplant Unit, TR-06100 Ankara, Turkey. Hacettepe Univ, Sch Med, Dept Med, Ankara, Turkey. Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, Dept Infect Dis, Westmead, NSW 2145, Australia. St Vincents Hosp, Dept Clin Microbiol & Infect Dis, Darlinghurst, NSW 2010, Australia. Inst Salud Carlos III, Dept Mycol, Spanish Natl Ctr Microbiol, Madrid, Spain. United Arab Emirates Med Sch, Dept Med, Al Ain, U Arab Emirates. RP Anaissie, EJ (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, 4301 W Markham,Slot 816, Little Rock, AR 72205 USA. EM anaissieeliasj@uams.edu RI Nucci, Marcio/G-4515-2012; Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014; OI Nucci, Marcio/0000-0003-4867-0014; Dignani, Maria Cecilia/0000-0002-7446-6183; Johnson, Melissa/0000-0002-6606-9460; Tortorano, Anna Maria/0000-0003-2093-8250; Herbrecht, Raoul/0000-0002-9381-4876; Denning, David/0000-0001-5626-2251; Jacobson, Robert/0000-0002-6355-8752; Hope, William/0000-0001-6187-878X NR 18 TC 2 Z9 2 U1 0 U2 2 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 OCT 15 PY 2006 VL 43 IS 8 BP 1031 EP 1039 DI 10.1086/509116 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 086IE UT WOS:000240666200013 PM 16983616 ER PT J AU Spanakis, EK Aperis, G Mylonakis, E AF Spanakis, Elias K. Aperis, George Mylonakis, Eleftherios TI New agents for the treatment of fungal infections: Clinical efficacy and gaps in coverage SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID LIPOSOMAL AMPHOTERICIN-B; EMPIRICAL ANTIFUNGAL THERAPY; CELL TRANSPLANT RECIPIENTS; DOUBLE-BLIND; ESOPHAGEAL CANDIDIASIS; INVASIVE ASPERGILLOSIS; PERSISTENT FEVER; SALVAGE TREATMENT; MICAFUNGIN FK463; OPEN-LABEL AB The incidence of fungal infections has increased globally, and the introduction of the newer triazoles and echinocandin antifungals is a more-than-welcome and long overdue development. In this report, we review the clinical trials evaluating the therapeutic efficacy of these new antifungal agents and examine possible gaps in coverage. Voriconazole has become the primary treatment for most forms of invasive aspergillosis in a number of centers, posaconazole offers a broad antifungal spectrum, and echinocandins are fungicidal against most Candida species. Moreover, the new agents are active against some fungi that are resistant to amphotericin B, may have a role in the management of fever and neutropenia, and provide exciting options for combination antifungal therapy. However, significant questions remain, including the management of breakthrough infections and treatment failures and the efficacy of the new antifungal agents against less common fungi. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIAID NIH HHS [K08 AI63084-01] NR 35 TC 87 Z9 91 U1 0 U2 3 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 OCT 15 PY 2006 VL 43 IS 8 BP 1060 EP 1068 DI 10.1086/507891 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 086IE UT WOS:000240666200018 PM 16983621 ER PT J AU Hamill, RJ AF Hamill, Richard J. TI Free fluconazole for cryptococcal meningitis: Too little of a good thing? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AMPHOTERICIN-B; ANTIRETROVIRAL THERAPY; AIDS; NEOFORMANS; DISEASE C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Hamill, RJ (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM rhamill@bcm.tmc.edu NR 16 TC 11 Z9 14 U1 1 U2 3 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 OCT 15 PY 2006 VL 43 IS 8 BP 1074 EP 1076 DI 10.1086/507900 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 086IE UT WOS:000240666200020 PM 16983623 ER PT J AU Choi, MY Romer, AI Hu, M Lepourcelet, M Mechoor, A Yesilaltay, A Krieger, M Gray, PA Shivdasani, RA AF Choi, Michael Y. Romer, Anthony I. Hu, Michael Lepourcelet, Maina Mechoor, Ambili Yesilaltay, Ayce Krieger, Monty Gray, Paul A. Shivdasani, Ramesh A. TI A dynamic expression survey identifies transcription factors relevant in mouse digestive tract development SO DEVELOPMENT LA English DT Article DE transcription factor; organogenesis; differentiation; Isx; stomach; intestine; mouse ID RECEPTOR CLASS-B; DENSITY-LIPOPROTEIN RECEPTOR; EMBRYONAL GUT DEVELOPMENT; CDX2 MUTANT MICE; I SR-BI; SCAVENGER RECEPTOR; GENE-EXPRESSION; NUCLEAR RECEPTOR; TRANSGENIC MICE; INTESTINAL METAPLASIA AB Tissue-restricted transcription factors (TFs), which confer specialized cellular properties, are usually identified through sequence homology or cis-element analysis of lineage-specific genes; conventional modes of mRNA profiling often fail to report non-abundant TF transcripts. We evaluated the dynamic expression during mouse gut organogenesis of 1381 transcripts, covering nearly every known and predicted TF, and documented the expression of approximately 1000 TF genes in gastrointestinal development. Despite distinctive structures and functions, the stomach and intestine exhibit limited differences in TF genes. Among differentially expressed transcripts, a few are virtually restricted to the digestive tract, including Nr2e3, previously regarded as a photoreceptor-specific product. TFs that are enriched in digestive organs commonly serve essential tissue-specific functions, hence justifying a search for other tissue-restricted TFs. Computational data mining and experimental investigation focused interest on a novel homeobox TF, Isx, which appears selectively in gut epithelium and mirrors expression of the intestinal TF Cdx2. Isx-deficient mice carry a specific defect in intestinal gene expression: dysregulation of the high density lipoprotein (HDL) receptor and cholesterol transporter scavenger receptor class B, type I (Scarb1). Thus, integration of developmental gene expression with biological assessment, as described here for TFs, represents a powerful tool to investigate control of tissue differentiation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Neurosci, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NIDDK NIH HHS [F32DK066963, R01DK61139] NR 57 TC 41 Z9 43 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 OCT 15 PY 2006 VL 133 IS 20 BP 4119 EP 4129 DI 10.1242/dev.02537 PG 11 WC Developmental Biology SC Developmental Biology GA 088ZJ UT WOS:000240849300019 PM 16971476 ER PT J AU Im, JS Tapinos, N Chae, GT Illarionov, PA Besra, GS DeVries, GH Modlin, RL Sieling, PA Rambukkana, A Porcelli, SA AF Im, Jin S. Tapinos, Nikos Chae, Gue-Tae Illarionov, Petr A. Besra, Gurdyal S. DeVries, George H. Modlin, Robert. L. Sieling, Peter A. Rambukkana, Anura Porcelli, Steven A. TI Expression of CD1d molecules by human Schwann cells and potential interactions with immunoregulatory invariant NK T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR EXPRESSION; C VIRUS-INFECTION; MYCOBACTERIUM-LEPRAE; GLYCOLIPID ANTIGENS; MULTIPLE-SCLEROSIS; PERIPHERAL-NERVE; IN-VITRO; RECOGNITION; LEPROSY; ACTIVATION AB CD1d-restricted NKT cells expressing invariant TCR alpha-chains (iNKT cells) produce both proinflammatory and anti-inflammatory cytokines rapidly upon activation, and are believed to play an important role in both host defense and immunoregulation. To address the potential implications of iNKT cell responses for infectious or inflammatory diseases of the nervous system, we investigated the expression of CD1d in human peripheral nerve. We found that CD1d was expressed on the surface of Schwann cells in situ and on primary or immortalized Schwann cell lines in culture. Schwann cells activated iNKT cells in a CD1d-dependent manner in the presence of a-galactosylceramide. Surprisingly, the cytokine production of iNKT cells stimulated by a-galactosylceramide presented by CD1d(+) Schwann cells showed a predominance of Th2-associated cytokines such as IL-5 and IL-13 with a marked deficiency of proinflammatory Th1 cytokines such as IFN-gamma or TNF-alpha. Our findings suggest a mechanism by which iNKT cells may restrain inflammatory responses in peripheral nerves, and raise the possibility that the expression of CD1d by Schwann cells could be relevant in the pathogenesis of infectious and inflammatory diseases of the peripheral nervous system. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Rockefeller Univ, Lab Bacterial Pathogenesis & Immunol, New York, NY 10021 USA. Catholic Univ, Inst Hansens Dis, Seoul, South Korea. Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Porcelli, SA (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. OI Modlin, Robert/0000-0003-4720-031X; Besra, Gurdyal/0000-0002-5605-0395 FU Medical Research Council [G0400421]; NCI NIH HHS [CA 133330]; NIAID NIH HHS [AI 45816, AI 051519, AI 45889, AI 064424, AI 51391]; NIAMS NIH HHS [AR 40312]; NINDS NIH HHS [NS 45187]; Wellcome Trust [072021/Z/03/Z] NR 60 TC 21 Z9 21 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2006 VL 177 IS 8 BP 5226 EP 5235 PG 10 WC Immunology SC Immunology GA 092JP UT WOS:000241093100035 PM 17015708 ER PT J AU Wunschmann, S Muller, HM Stipp, CS Hemler, ME Stapleton, JT AF Wuenschmann, Sabina Mueller, Hubert M. Stipp, Christopher S. Hemler, Martin E. Stapleton, Jack T. TI In vitro interaction between hepatitis C virus (HCV) envelope glycoprotein E2 and serum lipoproteins (LPs) results in enhanced cellular binding of both HCV E2 and LPs SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 11th International Symposium on Hepatitis C and Related Viruses CY OCT, 2004 CL Heidelberg, GERMANY ID HUMAN MONOCLONAL-ANTIBODIES; HIGH-DENSITY-LIPOPROTEINS; B TYPE-I; SCAVENGER RECEPTOR; CANDIDATE RECEPTOR; CORE PROTEIN; WHOLE-BLOOD; LIVER-CELLS; VERY-LOW; DC-SIGN AB Hepatitis C virus (HCV) particles in serum associate with lipoproteins (LPs), and the low-density lipoprotein receptor (LDLr) has been implicated in virus attachment and entry into cells. To clarify the basis of interactions between virus and LPs, we determined whether HCV interacts with human LPs via its envelope glycoprotein E2. The binding of serum-derived virus-like particles, HCV E2, and HCV E2-LP complexes to CD81 and LDLr was studied. Incubation of HCV E2 protein with human and bovine LPs (very low density, low density, and high density) enhanced the binding of both HCV E2 and LPs to CD4(+) lymphoblastoid (MOLT-4) cells, foreskin fibroblasts, and hepatocytes. The binding of HCV E2 to MOLT-4 cells was not enhanced when it was preincubated with lipid-free apoprotein B, which suggests that E2 interacts with the lipid moiety of human lipoproteins. The LP interaction was specific for HCV E2-incubation of HIV gp120 with LPs did not enhance gp120 binding to MOLT-4 cells. The enhanced HCV E2 binding required expression of both human CD81 and LDLr. These data suggest that HCV E2 associates with LDL and that the resulting complex enhances binding of both ligands to cells, which may contribute to the finding that HCV-infected individuals have significantly lower levels of LDL than control subjects. C1 Iowa City Vet Adm Med Ctr, Dept Internal Med, Iowa City, IA 52242 USA. Iowa City Vet Adm Med Ctr, Dept Res, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Iowa City, IA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Connex GmbH, Martinsried, Germany. RP Stapleton, JT (reprint author), Iowa City Vet Adm Med Ctr, Dept Internal Med, SW54,GH 200 Hawkins Dr, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu FU NIAID NIH HHS [AI58740] NR 50 TC 18 Z9 21 U1 0 U2 1 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 OCT 15 PY 2006 VL 194 IS 8 BP 1058 EP 1067 DI 10.1086/507647 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 084QC UT WOS:000240548500006 PM 16991080 ER PT J AU Cilmi, SA Karalius, BJ Choy, W Smith, RN Butterton, JR AF Cilmi, Salvatore A. Karalius, Brad J. Choy, Wendy Smith, R. Neal Butterton, Joan R. TI Fabry disease in mice protects against lethal disease caused by Shiga toxin-expressing enterohemorrhagic Escherichia coli SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 105th General Meeting of the American-Society-for-Microbiology CY JUN 05-09, 2005 CL Atlanta, GA SP Amer Soc Microbiol ID HEMOLYTIC-UREMIC SYNDROME; ALPHA-GALACTOSIDASE; DEFICIENT MICE; MOUSE MODEL; O157-H7; PIGLETS AB Fabry disease is an X-linked recessive disorder in which affected persons lack alpha-galactosidase A (alpha- GalA), which leads to excess glycosphingolipids in tissues, mainly globotriaosylceramide (Gb3). Gb3 is the cellular receptor for Shiga toxin (Stx), the primary virulence factor of enterohemorrhagic Escherichia coli. alpha-GalA-knockout mice were significantly protected against lethal intraperitoneal doses of Stx2 or oral doses of Stx2-expressing bacteria, compared with wild-type (wt) control mice. Kidneys of moribund wt mice revealed tubular necrosis, but no histopathologic changes were observed in Gb3-overexpressing mice. Reducing Gb3 levels in alpha-GalA-knockout mice by the intravenous injection of recombinant human a- GalA restored the susceptibility of knockout mice to lethal doses of Stx2. These results suggest that excess amounts of Gb3 in alpha-GalA-deficient mice may impair toxin delivery to susceptible tissues. C1 Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Butterton, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM jbutterton@partners.org FU NIAID NIH HHS [K08 AI059072]; NIDDK NIH HHS [R01 DK59010] NR 16 TC 17 Z9 17 U1 0 U2 3 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 OCT 15 PY 2006 VL 194 IS 8 BP 1135 EP 1140 DI 10.1086/507705 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 084QC UT WOS:000240548500015 PM 16991089 ER PT J AU Badaro, R Lobo, I Munos, A Netto, EM Modabber, F Campos-Neto, A Coler, RN Reed, SG AF Badaro, Roberto Lobo, Iza Munos, Alvaro Netto, Eduardo M. Modabber, Farrokh Campos-Neto, Antonio Coler, Rhea N. Reed, Steven G. TI Immunotherapy for drug-refractory mucosal leishmaniasis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd World Congress on Leishmaniasis CY APR 10-15, 2005 CL Palermo, ITALY ID COLONY-STIMULATING FACTOR; AMERICAN CUTANEOUS LEISHMANIASIS; LINKED-IMMUNOSORBENT-ASSAY; VISCERAL LEISHMANIASIS; IMMUNE-RESPONSES; CYTOKINE PROFILE; RHGM-CSF; T-CELL; VACCINE; PROTEIN AB Background. Pentavalent antimony (Sb-v) the mainstay therapy for mucosal leishmaniasis (ML), but it is toxic, and relapses are common. Immunotherapy using a mixture of killed parasites, with or without bacille Calmette-Guerin, is an alternative but is used sporadically because of inconsistent results. Methods. We developed a defined immunotherapeutic antigen preparation for use in an observational, open-label trial to treat 6 patients with ML with a history of Sb-v therapy failure. All patients were treated with the antigens thiol-specific antioxidant, Leishmania major stress inducible protein 1, Leishmania elongation initiation factor, and Leishmania heat shock protein 83, plus granulocyte-macrophage colony-stimulating factor. Patients underwent clinical and pathological evaluations before the initiation of immunotherapy and at 3, 6, 9, 12, 18, 24, and 60 months after. Results. One month after the third injection, 1 patient showed complete clinical remission (CC) and remained disease free for the duration of the study. At the 9-month follow-up examination, 5 patients showed CC, and all patients were asymptomatic at a subsequent 5-year follow-up examination. Conclusions. These data support the concept that vaccine therapy with a defined antigen combination, used with standard chemotherapy, is a safe and effective approach to treat drug-refractory ML. C1 Infect Dis Res Inst, Seattle, WA 98104 USA. Forsyth Inst, Boston, MA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Drugs Neglected Dis Initiat, Geneva, Switzerland. Univ Fed Bahia, Salvador, BA, Brazil. RP Reed, SG (reprint author), Infect Dis Res Inst, 1124 Columbia St,Suite 400, Seattle, WA 98104 USA. EM sreed@idri.org RI Netto, Eduardo/D-1432-2013 OI Netto, Eduardo/0000-0003-1691-6761 FU NIAID NIH HHS [AI25038, AI36810]; NIGMS NIH HHS [GM08347] NR 45 TC 38 Z9 40 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 OCT 15 PY 2006 VL 194 IS 8 BP 1151 EP 1159 DI 10.1086/507708 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 084QC UT WOS:000240548500017 PM 16991091 ER PT J AU Makris, N Kaiser, J Haselgrove, C Seidman, LJ Biederman, J Boriel, D Valera, EM Papadimitriou, GA Fischl, B Caviness, VS Kennedy, DN AF Makris, Nikos Kaiser, Jonathan Haselgrove, Christian Seidman, Larry J. Biederman, Joseph Boriel, Denise Valera, Eve M. Papadimitriou, George A. Fischl, Bruce Caviness, Verne S., Jr. Kennedy, David N. TI Human cerebral cortex: A system for the integration of volume- and surface-based representations SO NEUROIMAGE LA English DT Article DE human cerebral cortex; cortical thickness; cortical surface area; MRI; morphometry ID ANATOMICALLY SPECIFIED METHOD; CORTICAL SURFACE; RHESUS-MONKEY; COORDINATE SYSTEM; HUMAN NEOCORTEX; CELL-MIGRATION; VISUAL-CORTEX; BRAIN SCIENCE; MRI; NEURONS AB We describe an MRI-based system for topological analysis followed by measurements of topographic features for the human cerebral cortex that takes as its starting point volumetric segmentation data. This permits interoperation between volume-based and surface-based topographic analysis and extends the functionality of many existing segmentation schemes. We demonstrate the utility of these operations in individual as well as to group analysis. The methodology integrates analyses of cortical segmentation data generated by manual and semi-automated volumetric morphometry routines (such as the program cardviews) with the procedures of the FreeSurfer program to generate a cortical ribbon of the cerebrum and perform cortical topographic measurements (including thickness, surface area and curvature) in individual subjects as well as in subject populations. This system allows the computation of topographical cortical measurements for segmentation data generated from manual and semi-automated volumetric sources other than FreeSurfer. These measurements can be regionally specific and integrated with systems of cortical parcellation that subdivides the neocortex into gyral-based parcellation units (PUs). This system of topographical analysis of the cerebral cortex is consistent with current views of cortical development and neural systems organization of the human and non-human primate brain. (c) 2006 Elsevier Inc. All rights reserved. C1 MGH E, Ctr Morphometr Anal, Charlestown, MA 02129 USA. Dept Neurol, Boston, MA 02129 USA. Dept Psychiat, Boston, MA 02129 USA. NMR Ctr, Boston, MA 02115 USA. A Martinos Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Makris, N (reprint author), MGH E, Ctr Morphometr Anal, 149 13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NCRR NIH HHS [P41RR14075]; NICHD NIH HHS [HD 62152]; NIMH NIH HHS [F32 MH065040-01A1, MH 57934, MH-16259] NR 81 TC 41 Z9 42 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2006 VL 33 IS 1 BP 139 EP 153 DI 10.1016/j.neuroimage.2006.04.220 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 093ZW UT WOS:000241209800016 PM 16920366 ER PT J AU Kuperberg, GR Lakshmanan, BM Caplan, DN Holcomb, PJ AF Kuperberg, Gina R. Lakshmanan, Balaji M. Caplan, David N. Holcomb, Phillip J. TI Making sense of discourse: An fMRI study of causal inferencing across sentences SO NEUROIMAGE LA English DT Review DE language; discourse; sentences; fMRI; inferences; causal relationships; coherence; semantics; temporal cortex; inferior prefrontal cortex; dorsolateral prefrontal cortex; frontomedian cortex ID EVENT-RELATED FMRI; INFERIOR PREFRONTAL CORTEX; 2 CEREBRAL HEMISPHERES; LATENT SEMANTIC ANALYSIS; MEDIAL FRONTAL-CORTEX; VERBAL WORKING-MEMORY; TEXT COMPREHENSION; FUNCTIONAL MRI; CORTICAL SURFACE; BRAIN ACTIVITY AB To build up coherence between sentences (comprehend discourse), we must draw inferences, i.e. activate and integrate information that is not actually stated. We used event-related fMRI to determine the localization and extent of brain activity mediating causal inferencing across short, three-sentence scenarios. Participants read and made causal coherence judgments to sentences that were highly causally related, intermediately related or unrelated to their preceding two-sentence contexts. The highly related and intermediately related scenarios were matched in terms of semantic similarities between their individual component words. A pre-rating study established that causal inferences were generated to the intermediately related but not to the highly related or unrelated scenarios. In the scanner, sentences that were intermediately related (relative to highly related or unrelated) to their preceding contexts were associated with longer judgment reaction times and sustained increases in hemodynamic activity within left lateral temporal/inferior parietal/prefrontal cortices, the right inferior prefrontal gyrus and bilateral superior medial prefromal cortices. In contrast, sentences that were unrelated (relative to highly related) to their preceding contexts were associated with only transient increases in activity (at, but not after, the peak of the hemodynamic response) within the right lateral temporal cortex and the right inferior prefrontal gyros. These data suggest that, to make sense of discourse, we activate a large bilateral cortical network in response to what is not explicitly stated. We suggest that this network reflects the activation, retrieval and integration of information from long-term semantic memory into incoming discourse structure during causal inferencing. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. MGH, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY-2,Bldg 149,13th St, Charlestown, MA 02129 USA. EM kuperber@nmr.mgh.harvard.edu FU NICHD NIH HHS [R01 HD025889, R01 HD025889-15, R01 HD025889-16, R01 HD025889-17]; NIMH NIH HHS [R01 MH071635] NR 103 TC 81 Z9 83 U1 7 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2006 VL 33 IS 1 BP 343 EP 361 DI 10.1016/j.neuroimage.2006.06.001 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 093ZW UT WOS:000241209800034 PM 16876436 ER PT J AU Bennett, CM de Jong, JLO Neufeld, EJ AF Bennett, Carolyn M. de Jong, Jill L. O. Neufeld, Ellis J. TI Targeted ITP strategies: Do they elucidate the biology of ITP and related disorders? SO PEDIATRIC BLOOD & CANCER LA English DT Article; Proceedings Paper CT 2nd Expert Meeting of the Intercontinental-Childhood-ITP Study-Group (ICIS) CY SEP 16-18, 2006 CL Yverdon, SWITZERLAND SP Intercontinental Childhood ITP Study Grp DE autoimmune pancytopenia; rituximab; thrombocytopenia ID IDIOPATHIC THROMBOCYTOPENIC PURPURA; COMMON VARIABLE IMMUNODEFICIENCY; AUTOIMMUNE HEMOLYTIC-ANEMIA; B-CELL DEPLETION; RITUXIMAB TREATMENT; CYCLOSPORINE-A; EVANS-SYNDROME; CHILDREN; ADULTS; TERM AB An elusive goal in hematology is a detailed understanding of autoimmune blood disorders including idiopathic (immune) thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AlHA), and Evans Syndrome. While it is clear that these disorders have an autoimmune pathophysiology, the exact mechanisms are not clear. Agents that target the immune system specifically, such as rituximab and tacrolimus, are currently being used clinically with favorable results. Targeted therapy may be useful not only in treating these difficult diseases, but also may provide clues to the underlying disease pathophysiology. Carefully designed studies using targeted therapy may provide biologic predictors of disease severity, as well as predictors of response to therapy. Pediatr Blood Cancer 2006;47:706-709. (c) 2006 Wiley-Liss, Inc. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol, KFRL 8210,300 Longwood Ave, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011 NR 20 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT 15 PY 2006 VL 47 IS 5 SU S BP 706 EP 709 DI 10.1002/pbc.20974 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 082RT UT WOS:000240405600021 PM 16933263 ER PT J AU Atlas, SJ AF Atlas, Steven J. TI Minimum 25-year outcome and functional assessment of lumbar discectomy - Point of view SO SPINE LA English DT Editorial Material ID TRIALS; SPINE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, 9th Floor,50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD OCT 15 PY 2006 VL 31 IS 22 BP 2600 EP 2601 DI 10.1097/01.brs.0000240725.96698.22 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 098KK UT WOS:000241519200015 ER PT J AU Demetri, GD van Oosterom, AT Garrett, CR Blackstein, ME Shah, MH Verweij, J McArthur, G Judson, IR Heinrich, MC Morgan, JA Desai, J D Fletcher, C George, S Bello, CL Huang, X Baum, CM Casali, PG AF Demetri, George D. van Oosterom, Allan T. Garrett, Christopher R. Blackstein, Martin E. Shah, Manisha H. Verweij, Jaap McArthur, Grant Judson, Ian R. Heinrich, Michael C. Morgan, Jeffrey A. Desai, Jayesh D Fletcher, Christopher George, Suzanne Bello, Carlo L. Huang, Xin Baum, Charles M. Casali, Paolo G. TI Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial SO LANCET LA English DT Article ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; ACQUIRED-RESISTANCE; IN-VIVO; SU11248; KIT; MUTATIONS; LEIOMYOSARCOMAS; PROGRESSION; MANAGEMENT AB Background No effective therapeutic options for patients with unresectable imatinib-resistant gastrointestinal stromal tumour are available. We did a randomised, double-blind, placebo-controlled, multicentre, international trial to assess tolerability and anticancer efficacy of sunitinib, a multitargeted tyrosine kinase inhibitor, in patients with advanced gastrointestinal stromal tumour who were resistant to or intolerant of previous treatment with imatinib. Methods Blinded sunitinib or placebo was given orally once daily at a 50-mg starting dose in 6-week cycles with 4 weeks on and 2 weeks off treatment. The primary endpoint was time to tumour progression. Intention-to-treat, modified intention-to-treat, and per-protocol analyses were done. This study is registered at ClinicalTrials.gov, number NCT00075218. Findings 312 patients were randomised in a 2:1 ratio to receive sunitinib (n=207) or placebo (n=105); the trial was unblinded early when a planned interim analysis showed significantly longer time to tumour progression with sunitinib. Median time to tumour progression was 27.3 weeks (95% CI 16.0-32.1) in patients receiving sunitinib and 6.4 weeks (4.4-10.0) in those on placebo (hazard ratio 0.33; p<0.0001). Therapy was reasonably well tolerated; the most common treatment-related adverse events were fatigue, diarrhoea, skin discolouration, and nausea. Interpretation We noted significant clinical benefit, including disease control and superior survival, with sunitinib compared with placebo in patients with advanced gastrointestinal stromal tumour after failure and discontinuation of imatinab. Tolerability was acceptable. C1 Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Gen Med Oncol, Leuven Canc Inst, Louvain, Belgium. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Univ Toronto, Toronto, ON, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Univ Melbourne, St Vincents Hosp, Dept Med, Parkville, Vic 3052, Australia. Univ Melbourne, Peter MacCallum Canc Ctr, Parkville, Vic 3052, Australia. Royal Marsden Hosp, Sutton, Surrey, England. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Pfizer Global Res & Dev, La Jolla, CA USA. Ist Nazl Tumori, I-20133 Milan, Italy. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. EM gdemetri@partners.org RI casali, Paolo Giovanni/D-1524-2017 OI casali, Paolo Giovanni/0000-0003-4056-8023 NR 38 TC 1282 Z9 1372 U1 7 U2 47 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD OCT 14 PY 2006 VL 368 IS 9544 BP 1329 EP 1338 DI 10.1016/S0140-6736(06)69446-4 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 096PA UT WOS:000241388100029 PM 17046465 ER PT J AU Peltan, ID Thomas, AV Mikhailenko, I Strickland, DK Hyman, BT von Arnim, CAF AF Peltan, Ithan D. Thomas, Anne V. Mikhailenko, Irina Strickland, Dudley K. Hyman, Bradley T. von Arnim, Christine A. F. TI Fluorescence lifetime imaging microscopy (FLIM) detects stimulus-dependent phosphorylation of the low density lipoprotein receptor-related protein (LRP) in primary neurons SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE LRP; phosphorylation; FLIM; FRET; PDGF; APP ID AMYLOID PRECURSOR PROTEIN; RESONANCE ENERGY-TRANSFER; GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; APOLIPOPROTEIN-E; KINASE-C; CORECEPTOR FUNCTION; ALZHEIMERS-DISEASE; CYTOPLASMIC DOMAIN; CELL-MIGRATION AB The low-density lipoprotein receptor-related protein (LRP) is a large, endocytic receptor involved in intracellular signalling. LRP acts as a co-receptor with the PDGF-receptor (PDGF-r) for platelet-derived growth factor (PDGF). PDGF-r and Src-kinases induce tyrosine-phosphorylation of LRP. We used fluorescence lifetime imaging microscopy (FLIM) to specifically detect LRP phosphorylation, measure its extent and localization in intact cells, and assess its effects upon LRP-APP interaction. Robust phosphorylation of LRP throughout the cell was observed after overexpression of Src-kinase. This depended on LRP's distal NPXY domain. By contrast, activation of the PDGF-r resulted in phosphorylation of the subpopulation of LRP at or near the cell surface. PDGF activation triggered phosphorylation of endogenous LRP in primary neurons. LRP is also a trafficking receptor for the Alzheimer-related molecule amyloid-precursor-protein (APP). PDGF stimulation did not affect LRP APP interactions. This approach allows exquisite subcellular resolution of specific LRP post-translational changes and protein-protein interactions of endogenous proteins in intact cells. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Peltan, Ithan/0000-0003-1730-234X FU NIA NIH HHS [AG12406] NR 21 TC 8 Z9 8 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 13 PY 2006 VL 349 IS 1 BP 24 EP 30 DI 10.1016/j.bbrc.2006.07.212 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 086CF UT WOS:000240650000005 PM 16930548 ER PT J AU Tokuda, T Salem, SA Allsop, D Mizuno, T Nakagawa, M Qureshi, MM Locascio, JJ Schlossmacher, MG El-Agnaf, OMA AF Tokuda, Takahiko Salem, Sultan A. Allsop, David Mizuno, Toshiki Nakagawa, Masanori Qureshi, Mohamed M. Locascio, Joseph J. Schlossmacher, Michael G. El-Agnaf, Omar M. A. TI Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Parkinson disease; neurodegenerative diseases; alpha-synuclein; cerebrospinal fluid; ELISA; biomarker; diagnosis ID ALZHEIMERS-DISEASE; LOCUS TRIPLICATION; SERINE-PROTEASE; HUMAN PLASMA; BRAIN; DUPLICATION; DEMENTIA; MUTATION; NEUROSIN; TAU AB There is ample biochemical, pathological, and genetic evidence that the metabolism of alpha-synuclein (alpha-syn) plays a crucial role in the pathogenesis of Parkinson disease (PD). To examine whether quantification of alpha-syn in cerebrospinal fluid (CSF) is potentially informative in the diagnosis of PD, we developed a specific ELISA system and measured the concentration of alpha-syn in CSF from 33 patients with PD (diagnosed according to UK PD Society Brain Bank criteria) and 38 control subjects including 9 neurologically healthy individuals. We found that PD patients had significantly lower alpha-syn levels in their CSF than the control groups (p < 0.0001) even after adjusting for gender and age. Age was independently associated with lower a-syn levels. Logistic regression analysis showed that reduction in CSF alpha-syn served as a significant predictor of PD beyond age and gender alone (area under ROC curve, c = 0.882). Furthermore, we observed a close inverse correlation between alpha-syn levels in CSF and assigned Hoehn and Yahr score in this cohort of 71 living subjects (P < 0.0001), even after adjusting for age. These findings identify in the quantification of alpha-syn from CSF a potential laboratory marker to aid the clinical diagnosis of PD. (c) 2006 Elsevier Inc. All rights reserved. C1 United Arab Emirates Univ, Dept Biochem, Fac Med & Hlth Sci, Al Ain 17666, U Arab Emirates. Univ Lancaster, Dept Biol Sci, Biomed Sci Unit, Lancaster LA1 4YQ, England. Kyoto Prefectural Univ Med, Dept Neurol, Kyoto 6020841, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP El-Agnaf, OMA (reprint author), United Arab Emirates Univ, Dept Biochem, Fac Med & Hlth Sci, Al Ain 17666, U Arab Emirates. EM o.elagnaf@uaeu.ac.ae RI Allsop, David/B-9725-2008 OI Allsop, David/0000-0002-0513-5575 NR 24 TC 228 Z9 233 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 13 PY 2006 VL 349 IS 1 BP 162 EP 166 DI 10.1016/j.bbrc.2006.08.024 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 086CF UT WOS:000240650000021 PM 16930553 ER PT J AU Devgan, V Nguyen, BC Oh, H Dotto, GP AF Devgan, Vikram Nguyen, Bach-Cuc Oh, Heysun Dotto, G. Paolo TI p21(WAF1/Cip1) suppresses keratinocyte differentiation independently of the cell cycle through transcriptional up-regulation of the IGF-I gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUSTAINED ACTIVATION; INDUCED APOPTOSIS; HUMAN SKIN; GROWTH; EXPRESSION; P21(CIP1/WAF1); RECEPTOR; INHIBITOR; MITOGEN; ALPHA AB p21 plays a dual role in keratinocyte growth and differentiation control. It restricts the number of keratinocyte stem cell populations while inhibiting the later stages of differentiation independently of the cell cycle. The molecular/biochemical mechanism for the differentiation suppressive function of p21 is unknown. Here we show that elevated p21 expression leads to activation of MAPK family members in a keratinocyte-specific and cell cycle-independent manner, and up-regulation of MAPK activity can explain the inhibitory effects of p21 on differentiation. p21 induces transcription of several genes with MAPK activation potential. Although several of these genes are induced by p21 in a MAPK-dependent manner, expression of IGF-I is induced upstream of MAPK activation. IGF-I stimulation is by itself sufficient to cause MAPK activation and inhibit differentiation and suppression of IGF-I signaling by knock down of the cognate receptor (IGF-R1), diminishing the ability of p21 to activate MAPK and suppress differentiation. Thus, in keratinocytes, the ability of p21 to suppress differentiation can be explained by cell type-specific activation of the MAPK cascade by transcriptional up-regulation of the IGF-I gene. C1 Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, Chem Bovaresses 155, CH-1066 Epalinges, Switzerland. EM Gian-Paolo.Dotto@unil.ch FU NCI NIH HHS [CA73796, CA16038] NR 43 TC 21 Z9 21 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 OCT 13 PY 2006 VL 281 IS 41 BP 30463 EP 30470 DI 10.1074/jbc.M604684200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092CZ UT WOS:000241075900021 PM 16912042 ER PT J AU Lu, GW Maeda, H Reddy, SV Kurihara, N Leach, R Anderson, JL Roodman, GD AF Lu, Ganwei Maeda, Hidefumi Reddy, Sakamuri V. Kurihara, Noriyoshi Leach, Robin Anderson, Judith L. Roodman, G. David TI Cloning and characterization of the annexin II receptor on human marrow stromal cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEOCLAST-STIMULATING FACTOR; HUMAN-BONE MARROW; A2 HETEROTETRAMER; GENE FAMILY; MEMBRANE; CULTURES; IDENTIFICATION; RESORPTION; DIFFERENTIATION; PRECURSORS AB Annexin II is a heterotetramer, consisting of two 11-kDa (p11) and two 36-kDa (p36) subunits, that is produced by osteoclasts and stimulates osteoclast formation. However, its receptor is unknown. We showed that annexin II binds to normal primary human marrow stromal cells and the Paget's marrow-derived PSV10 stromal cell line to induce osteoclast formation. I-125-Labeled annexin II binding assays with PSV10 cells demonstrated that there was a single class of annexin II receptors with a K-d of 5.79 nM and B-max of 2.13 x 10(5) receptors/cell. Annexin III or annexin V did not bind this receptor. Using I-125-labeled annexin II binding to screen NIH3T3 transfected with a human marrow cDNA expression library, we identified a putative annexin II receptor clone, which encoded a novel 26-kDa type I membrane receptor protein when expressed in HEK 293 cells. HEK 293 cells transformed with the cloned annexin II receptor cDNA showed a similar binding affinity to annexin II as that observed in PSV10 cells. Chemical cross-linking experiments with biotinylated annexin II and intact PSV10 cells identified a 55-kDa band on Western blot analysis that reacted with both an anti-p11 antibody and streptavidin but not anti-p36 antibody. A rabbit polyclonal antibody raised against the putative recombinant annexin II receptor also recognized the same 26-kDa protein band detected in PSV10 cells. Importantly, the annexin II receptor antibody dose-dependently blocked the stimulatory effects of annexin II on human osteoclast formation, demonstrating that the receptor mediates the effects of annexin II on osteoclast formation. C1 VA Pittsburgh Healthcare Syst, Med Hematol Oncol 151U, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA 15240 USA. Kyushu Univ Hosp, Fukuoka 8128581, Japan. Med Univ S Carolina, Childrens Res Inst, Dept Pediat, Charleston, SC 29425 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, Med Hematol Oncol 151U, Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu FU NIA NIH HHS [AG13625]; NIAMS NIH HHS [AR41336, AR44603] NR 37 TC 16 Z9 18 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 13 PY 2006 VL 281 IS 41 BP 30542 EP 30550 DI 10.1074/jbc.M607072200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092CZ UT WOS:000241075900030 PM 16895901 ER PT J AU Isayama, T Alexeev, D Makino, CL Washington, I Nakanishi, K Turro, NJ AF Isayama, T. Alexeev, D. Makino, C. L. Washington, I. Nakanishi, K. Turro, N. J. TI An accessory chromophore in red vision SO NATURE LA English DT Article ID DRAGON FISH; CHLOROPHYLL C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Columbia Univ, Dept Chem, New York, NY 10027 USA. RP Isayama, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM cmakino@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 NR 7 TC 10 Z9 12 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 12 PY 2006 VL 443 IS 7112 BP 649 EP 649 DI 10.1038/443649a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093HX UT WOS:000241160500035 PM 17035994 ER PT J AU Schneider, LS Tariot, PN Dagerman, KS Davis, SM Hsiao, JK Ismail, MS Lebowitz, BD Lyketsos, CG Ryan, JM Stroup, TS Sultzer, DL Weintraub, D Lieberman, JA AF Schneider, Lon S. Tariot, Pierre N. Dagerman, Karen S. Davis, Sonia M. Hsiao, John K. Ismail, M. Saleem Lebowitz, Barry D. Lyketsos, Constantine G. Ryan, J. Michael Stroup, T. Scott Sultzer, David L. Weintraub, Daniel Lieberman, Jeffrey A. CA CATIE-AD Study Grp TI Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIALS; DIAGNOSTIC-CRITERIA; INTERNATIONAL WORKSHOP; CEREBROVASCULAR EVENTS; NEUROLEPTIC TREATMENT; DEMENTIA TRIALS; METAANALYSIS; DEPRESSION; PSYCHOSIS; RISK AB BACKGROUND Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease. METHODS In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. RESULTS There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. C1 Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. Banner Alzheimers Inst, Phoenix, AZ USA. Quintiles, Res Triangle Pk, NC USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Johns Hopkins Univ, Johns Hopkins Bayview, Dept Psychiat, Baltimore, MD USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Coll Phys & Surg, New York, NY USA. RP Schneider, LS (reprint author), Univ So Calif, Keck Sch Med, 1510 San Pablo St,HCC 600, Los Angeles, CA 90033 USA. EM lschneid@usc.edu RI Stroup, Thomas/F-9188-2014 OI Adler, Lawrence/0000-0002-6619-2493; Stroup, Thomas/0000-0002-3123-0672 NR 33 TC 556 Z9 562 U1 3 U2 29 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 OCT 12 PY 2006 VL 355 IS 15 BP 1525 EP 1538 DI 10.1056/NEJMoa061240 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 093HW UT WOS:000241160400004 PM 17035647 ER PT J AU Hoppin, AG Katz, ES Kaplan, LM Lauwers, GY AF Hoppin, Alison G. Katz, Eliot S. Kaplan, Lee M. Lauwers, Gregory Y. TI A 15-year-old girl with severe obesity - Severe childhood obesity with obstructive sleep apnea, hypertension, impaired glucose tolerance progressing to type 2 diabetes mellitus, the polycystic ovary syndrome, and nonalcoholic steatohepatitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INSULIN-RESISTANCE; NUTRITION EXAMINATION; DAYTIME SLEEPINESS; METABOLIC SYNDROME; NATIONAL-HEALTH; RISK-FACTORS; WEIGHT-LOSS; CHILDREN; ADOLESCENTS; PREVALENCE C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Hoppin, AG (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 47 TC 9 Z9 9 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 12 PY 2006 VL 355 IS 15 BP 1593 EP 1602 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 093HW UT WOS:000241160400012 PM 17035653 ER PT J AU Marderosian, M Sharma, AP Funk, AP Vartanian, R Masri, J Jo, OD Gera, JF AF Marderosian, M. Sharma, A. P. Funk, A. P. Vartanian, R. Masri, J. Jo, O. D. Gera, J. F. TI Tristetraprolin regulates Cyclin D1 and c-myc mRNA stability in response to rapamycin in an Akt-dependent manner via p38 MAPK signaling SO ONCOGENE LA English DT Article DE akt; mTOR; rapamycin; cyclin D1; c-myc; tristetraprolin; mRNA stability ID ACTIVATED PROTEIN-KINASE; AU-RICH ELEMENTS; ENHANCED SENSITIVITY; MAMMALIAN-CELLS; BINDING PROTEIN; DOWN-REGULATION; TURNOVER; EXPRESSION; CANCER; TRANSLATION AB The differential expression of the critical cell cycle control proteins cyclin D1 and c-myc has been shown to result in Akt-dependent hypersensitivity of tumor cells to mTOR inhibitors. We have previously demonstrated that the differential utilization of internal ribosome entry sites within the mRNAs of these transcripts allows maintenance of protein synthesis in the face of rapamycin ( rapa) exposure in an Akt-dependent manner. Here, we demonstrate that in addition to this mechanism, cyclin D1 and c-myc mRNA stability is also coordinately regulated following rapa treatment depending on Akt activity status. We identify A/U-rich response elements within the 3' untranslated regions ( UTRs) of these transcripts, which confer the observed differential stabilities and show that the RNA-binding protein, tristetraprolin (TTP), interacts with these elements. We also present evidence that TTP accumulates in response to rapa exposure, binds to the cis-acting elements within the cyclin D1 and c-myc 3' UTRs and is differentially serine phosphorylated in an Akt-dependent manner. Furthermore, the differential phosphorylation status of TTP results in its sequestration by 14-3-3 proteins in quiescent Akt-containing cells. Finally, siRNA-mediated knockdown of TTP expression or inhibiting a known regulator of TTP phosphorylation, p38 MAP kinase, abolishes the effects on cyclin D1 and c-myc mRNA stability. We assume that the differential control of cyclin D1 and c-myc mRNA stability and translational efficiency constitutes a coordinate response to rapa contributing to the maintenance of expression of these determinants in rapa-resistant quiescent Akt-containing cells following exposure. C1 Greater Los Angeles VA Healthcare Syst, Dept Res & Dev, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Gera, JF (reprint author), Greater Los Angeles VA Healthcare Syst, Dept Res & Dev, Bldg 1,Rm C111A, Sepulveda, CA 91343 USA. EM gera@ucla.edu FU NCI NIH HHS [R01-CA-109312] NR 52 TC 81 Z9 84 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 12 PY 2006 VL 25 IS 47 BP 6277 EP 6290 DI 10.1038/sj.onc.1209645 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 094CY UT WOS:000241218200005 PM 16702957 ER PT J AU Kneipp, J Kneipp, H McLaughlin, M Brown, D Kneipp, K AF Kneipp, Janina Kneipp, Harald McLaughlin, Margaret Brown, Dennis Kneipp, Katrin TI In vivo molecular probing of cellular compartments with gold nanoparticles and nanoaggregates SO NANO LETTERS LA English DT Article ID SURFACE-ENHANCED RAMAN; MAMMALIAN-CELLS; MEDIATED ENDOCYTOSIS; SILVER ELECTRODE; SCATTERING SERS; LATE ENDOSOMES; RAT-LIVER; SPECTROSCOPY; DNA; LYSOSOMES AB Surface-enhanced Raman (SERS) signatures were measured from single living cells at different times after the uptake of gold nanoparticles. The spectra are indicative of chemical changes in the environment of the nanostructures over time. The increase of the SERS signal strength and parallel TEM studies indicate the formation of nanoaggregates providing optimum SERS enhancement for ultrasensitive probing inside the endosomal compartment. The results have implications for medical and biotechnology applications of SERS nanosensors in cells. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. RP Kneipp, J (reprint author), Fed Inst Mat Res & Testing, FG I-3,Richard Willstatter Str 11, D-12489 Berlin, Germany. EM jkneipp@janina-kneipp.de RI Kneipp, Katrin/B-1024-2011 FU NIDDK NIH HHS [DK38452, DK43341, DK57521] NR 51 TC 299 Z9 302 U1 12 U2 124 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD OCT 11 PY 2006 VL 6 IS 10 BP 2225 EP 2231 DI 10.1021/nl061517x PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 093GW UT WOS:000241157300011 PM 17034088 ER PT J AU Heinrich, MC Corless, CL Blanke, CD Demetri, GD Joensuu, H Roberts, PJ Eisenberg, BL von Mehren, M Fletcher, CDM Sandau, K McDougall, K Ou, WB Chen, CJ Fletcher, JA AF Heinrich, Michael C. Corless, Christopher L. Blanke, Charles D. Demetri, George D. Joensuu, Heikki Roberts, Peter J. Eisenberg, Burton L. von Mehren, Margaret Fletcher, Christopher D. M. Sandau, Katrin McDougall, Karen Ou, Wen-bin Chen, Chang-Jie Fletcher, Jonathan A. TI Molecular correlates of imatinib resistance in gastrointestinal stromal tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACQUIRED-RESISTANCE; KIT MUTATIONS; MISSENSE MUTATION; TYROSINE KINASE; PHASE-I; GENE; MESYLATE; PATIENT; INHIBITION; ACTIVATION AB Purpose Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem. Patients and Methods One hundred forty-seven patients with advanced, unresectable GISTs were enrolled onto a randomized, phase II clinical study of imatinib. Specimens from pretreatment and/or imatinib-resistant tumors were analyzed to identify molecular correlates of imatinib resistance. Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity. Results Molecular studies were performed using specimens from 10 patients with primary and 33 patients with secondary resistance. Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs. Secondary kinase mutations were rare in GISTs with primary resistance but frequently found in GISTs with secondary resistance (10% v 67%; P =.002). Evidence for clonal evolution and/or polyclonal secondary kinase mutations was seen in three (18.8%) of 16 patients. Secondary kinase mutations were nonrandomly distributed and were associated with decreased imatinib sensitivity compared with typical KIT exon II mutations. Using RNAi technology, we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways. Conclusion Different molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs. These findings have implications for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs. C1 Oregon Hlth & Sci Univ, Inst Canc, Dept Pathol, Div Hematol Oncol, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Div Surg Oncol, Lebanon, NH 03766 USA. Fox Chase Canc Ctr, Div Med Oncol, Philadelphia, PA 19111 USA. Novartis Pharmaceut, Hanover, NH USA. Univ Helsinki, Helsinki, Finland. Univ Turku, Dept Surg, Turku, Finland. RP Heinrich, MC (reprint author), R&D 19 3710 US Vet Hosp Rd, Portland, OR 97239 USA. EM Heinrich@ohsu.edu OI Joensuu, Heikki/0000-0003-0281-2507 NR 34 TC 413 Z9 437 U1 2 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2006 VL 24 IS 29 BP 4764 EP 4774 DI 10.1200/JCO.2006.06.2265 PG 11 WC Oncology SC Oncology GA 093TI UT WOS:000241191900015 PM 16954519 ER PT J AU Dunfee, RL Thomas, ER Gorry, PR Wang, JB Taylor, J Kunstman, K Wolinsky, SM Gabuzda, D AF Dunfee, Rebecca L. Thomas, Elaine R. Gorry, Paul R. Wang, Jianbin Taylor, Joann Kunstman, Kevin Wolinsky, Steven M. Gabuzda, Dana TI The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD4; envelope; neurotropism; microglia ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; CEREBROSPINAL-FLUID; ALVEOLAR MACROPHAGES; CD4 EXPRESSION; AIDS PATIENTS; LIVING CELLS; V3 SEQUENCES; MICROGLIA; BLOOD AB HIV infects tissue macrophages and brain microglia, which express lower levels of CD4 and CCR5 than CD4(+) T cells in peripheral blood. Mechanisms that enhance HIV tropism for macrophages in the CNS and other tissues are not well understood. Here, we identify an HIV envelope glycoprotein (Env) variant in the CD4-binding site of gp120, Asn 283 (N283), that is present at a high frequency in brain tissues from AIDS patients with HIV-associated dementia (HAD). N283 increases gp120 affinity for CD4 by decreasing the gp120-CD4 dissociation rate, enhancing the capacity of HIV Envs to use low levels of CD4 for virus entry and increasing viral replication in macrophages and microglia. Structural modeling suggests that the enhanced ability of Envs with N283 to use low levels of CD4 is due to a hydrogen bond formed with Gin 40 of CD4. N283 is significantly more frequent in brain-derived Envs from HAD patients (41%; n = 330) compared with non-HAD patients (8%; n = 151; P < 0.001). These findings suggest that the macrophage-tropic HIV Env variant N283 is associated with brain infection and dementia in vivo, representing an example of a HIV variant associated with a specific AIDS-related complication. C1 Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NINDS NIH HHS [R01 NS037277, NS37277] NR 48 TC 98 Z9 100 U1 2 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 OCT 10 PY 2006 VL 103 IS 41 BP 15160 EP 15165 DI 10.1073/pnas.0605513103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 094NX UT WOS:000241247300033 PM 17015824 ER PT J AU Javanbakht, H An, P Gold, B Petersen, DC O'Huigin, C Nelson, GW O'Brien, SJ Kirk, GD Detels, R Buchbinder, S Donfield, S Shulenin, S Song, B Perron, MJ Stremlau, M Sodroski, J Dean, M Winkler, C AF Javanbakht, Hassan An, Ping Gold, Bert Petersen, Desiree C. O'Huigin, Cohn Nelson, George W. O'Brien, Stephen J. Kirk, Gregory D. Detels, Roger Buchbinder, Susan Donfield, Sharyne Shulenin, Sergey Song, Byeongwoon Perron, Michel J. Stremlau, Matthew Sodroski, Joseph Dean, Michael Winkler, Cheryl TI Effects of human TRIM5 alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection SO VIROLOGY LA English DT Article DE TRIM5 alpha; single nucleotide polymorphism; HIV-1; HIV infections; disease susceptibility; genetics; haplotype ID RESTRICTION FACTOR TRIM5-ALPHA; BROAD-HOST-RANGE; HIV-1 INFECTION; RETROVIRUS RESTRICTION; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; TYPE-1 INFECTION; DRUG-USERS; OLD-WORLD; AIDS AB TRIM5 alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5 alpha on HIV-1 infection. in African Americans, the frequencies of two non-coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1-infected persons compared with uninfected subjects. By contrast, the frequency of the variant allele encoding TRIM5 alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5 alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5 alpha R136 protein. The 43Y variant of TRIM5 alpha was less efficient than the H43 variant at restricting HIV-1 and murine leukemia virus infections in cultured cells. The ancestral TRIM5 haplotype specifying no observed variant alleles appeared to be protective against infection, and the corresponding wild-type protein partially restricted HIV-1 replication in vitro. A single logistic regression model with a permutation test indicated the global corrected P value of < 0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Mol Genet Epidemiol Sec, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Lab Genom Divers, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Div AIDS, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Stellenbosch, Tygerberg Med Sch, Dept Med Virol, ZA-7505 Tygerberg, South Africa. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rho Inc, Chapel Hill, NC 27514 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Winkler, C (reprint author), NCI, Mol Genet Epidemiol Sec, Bldg 560,Room 21-19, Frederick, MD 21702 USA. EM winkler@ncifcrf.gov RI Kirk, Gregory/A-8484-2009; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI063987, AI28691] NR 53 TC 81 Z9 87 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 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2006 VL 354 IS 1 BP 15 EP 27 DI 10.1016/j.virol.2006.06.031 PG 13 WC Virology SC Virology GA 093OV UT WOS:000241178500003 PM 16887163 ER PT J AU Nelson, JE Tandon, N Mercado, AF Camhi, SL Ely, W Morrison, S AF Nelson, Judith E. Tandon, Nidhi Mercado, Alice F. Camhi, Sharon L. Ely, Wesley Morrison, Sean TI Brain dysfunction - Another burden for the chronically critically ill SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; CONFUSION ASSESSMENT METHOD; CHRONIC CRITICAL ILLNESS; DELIRIUM; VALIDATION; STAY; ICU; RELIABILITY; IMPAIRMENT AB Background: Chronic critical illness is a devastating syndrome of prolonged respiratory failure and other derangements. To our knowledge, no previous research has addressed brain dysfunction in the chronically critically ill, although this topic is important for medical decision making. Methods: We studied a prospective cohort of 203 consecutive, chronically critically ill adults transferred to our hospital's respiratory care unit (RCU) after tracheotomy for failure to wean. We measured prevalence and duration of coma and delirium during RCU treatment using the Confusion Assessment Method for the Intensive Care Unit with the Richmond Agitation-Sedation Scale. To assess survivors (at 3 and 6 months after RCU discharge), we used a validated telephone Confusion Assessment Method. Results: Before hospitalization, most (153 [75.4%]) of the 203 patients in the study were at home, completely independent (115 [56.7%]), and cognitively intact (116 [82.0%]). In the RCU, 61 (30.0%) were comatose throughout the stay. Approximately half of patients (66 of 142) who were not in coma were delirious. Patients spent an average of 17.9 days (range, 1-153 days) in coma or delirium (average RCU stay, 25.6 days). Half of survivors (79 of 160) had one of these disturbances at RCU discharge. At 6 months, three fourths (151) of the study patients were dead or institutionalized; of 85 survivors, 58 (68.2%) were too profoundly impaired to respond to telephone cognitive assessment, and 53 (62.4%) were dependent in all activities of daily living. Conclusions: Severe, prolonged, and permanent brain dysfunction is a prominent feature of chronic critical illness. These data, together with previous reports of symptom distress and rates of mortality and institutionalization, describe burdens for chronically critically ill patients receiving continued life-prolonging treatment and for their families. C1 CUNY Mt Sinai Sch Med, Div Pulm & Crit Care, Dept Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Hertzberg Palliat Care Inst, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. Vet Adm Tennessee Valley Geriatr Res, Educ & Clin Ctr, Nashville, TN USA. Vanderbilt Univ, Sch Med, Ctr Hlth Serv Res, Nashville, TN USA. Vanderbilt Univ, Sch Med, Dept Med, Div Allergy Pulmonary Crit Care Med, Nashville, TN USA. Bronx Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, New York, NY USA. RP Nelson, JE (reprint author), CUNY Mt Sinai Sch Med, Div Pulm & Crit Care, Dept Med, Box 1232,1 Gustave L Levy Pl, New York, NY 10029 USA. EM judith.nelson@mountsinai.org FU NIA NIH HHS [K02 AG024476, K24 AG022345, R01 AG21172, K23 AG01023] NR 40 TC 59 Z9 61 U1 4 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 9 PY 2006 VL 166 IS 18 BP 1993 EP 1999 DI 10.1001/archinte.166.18.1993 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 091VV UT WOS:000241057300009 PM 17030833 ER PT J AU Parashar, S Rumsfeld, JS Spertus, JA Reid, KJ Wenger, NK Krumholz, HM Amin, A Weintraub, WS Lichtman, J Dawood, N Vaccarino, V AF Parashar, Susmita Rumsfeld, John S. Spertus, John A. Reid, Kimberly J. Wenger, Nanette K. Krumholz, Harlan M. Amin, Alpesh Weintraub, William S. Lichtman, Judith Dawood, Nazeera Vaccarino, Viola CA PREMIER Registry Investigators TI Time course of depression and outcome of myocardial infarction SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; MAJOR DEPRESSION; ENHANCING RECOVERY; RISK SCORE; MORTALITY; EVENTS; SYMPTOMS; ANGINA; SEVERITY AB Background: Depression predicts worse outcomes after myocardial infarction (MI), but whether its time course in the month following MI has prognostic importance is unknown. Our objective was to evaluate the prognostic importance of transient, new, or persistent depression on outcomes at 6 months after MI. Methods: In a prospective registry of acute MI ( Prospective Registry Evaluating outcomes after Myocardial Infarction: Events and Recovery [PREMIER]), depressive symptoms were measured in 1873 patients with the Patient Health Questionnaire (PHQ) during hospitalization and 1 month after discharge and were classified as transient (only at baseline), new (only at 1 month), or persistent (at both times). Outcomes at 6 months included (1) all-cause rehospitalization or mortality and (2) health status (angina, physical limitation, and quality of life using the Seattle Angina Questionnaire). Results: Compared with nondepressed patients, all categories of depression were associated with higher rehospitalization or mortality rates, more frequent angina, more physical limitations, and worse quality of life. The adjusted hazard ratios for rehospitalization or mortality were 1.34, 1.71, and 1.42 for transient, new, and persistent depression, respectively (all P < .05). Corresponding odds ratios were 1.62, 2.73, and 2.64 (all P < .01) for angina and 1.69, 2.25, and 3.27 (all P < .05) for physical limitation. Depressive symptoms showed a stronger association with health status compared with traditional measures of disease severity. Conclusion: Depressive symptoms after MI, irrespective of whether they persist, subside, or newly develop in the first month after hospitalization, are associated with worse outcomes after MI. C1 Emory Univ, Sch Med, Dept Med, Div Gen Med, Atlanta, GA 30303 USA. Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA 30303 USA. Denver VA Med Ctr, Denver, CO USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Med, New Haven, CT USA. Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Christiana Hosp, Ctr Heart & Vasc Hlth, Wilmington, DE USA. RP Parashar, S (reprint author), Emory Univ, Sch Med, Dept Med, Div Gen Med, Fac Off Bldg,49 Jesse Hill Jr Dr, Atlanta, GA 30303 USA. EM smallik@emory.edu FU NCCDPHP CDC HHS [K01-DP000085-01]; NCRR NIH HHS [K12-RR17643, K23-RR023171, MO1-RR00039]; NHLBI NIH HHS [K24-HL077506, R01-HL68630]; NIA NIH HHS [R01-AG026255] NR 26 TC 95 Z9 98 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 9 PY 2006 VL 166 IS 18 BP 2035 EP 2043 DI 10.1001/archinte.166.18.2035 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 091VV UT WOS:000241057300016 PM 17030839 ER PT J AU Hartmann, CW Rhee, DJ AF Hartmann, Christine W. Rhee, Douglas J. TI The patient's journey: glaucoma SO BRITISH MEDICAL JOURNAL LA English DT Article C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Hlth Policy, Philadelphia, PA 19107 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Hartmann, CW (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Hlth Policy, Philadelphia, PA 19107 USA. EM cwhrtmnn@aol.com NR 0 TC 4 Z9 4 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD OCT 7 PY 2006 VL 333 IS 7571 BP 738 EP 739 DI 10.1136/bmj.38975.507188.7C PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 094OK UT WOS:000241248600021 PM 17023466 ER PT J AU Bai, JR Demirjian, A Sui, JH Marasco, W Callery, MP AF Bai, Jirong Demirjian, Aram Sui, Jianhua Marasco, Wayne Callery, Mark P. TI Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE histone deacetylase inhibitor; proteasome inhibitor; NF kappa B, Bcl-XL; pancreatic cancer ID NF-KAPPA-B; ANTITUMOR-ACTIVITY; MULTIPLE-MYELOMA; PHASE-II; GEMCITABINE; EXPRESSION; ADENOCARCINOMA; CHEMOTHERAPY; ACTIVATION; AGENTS AB Pancreatic cancer is a common and lethal malignancy. Pancreatic cancer cells overexpress multiple anti-apoptotic factors and death receptor decoys, and are strongly resistant to radiation and to 5-fluorouracil (5-FU)- or gemcitabine (Gem)-based chemotherapy regimens. We have found that low-dose proteasome inhibitor PS-341 and histone deacetylase inhibitor trichostatin A (TSA) synergistically induce cytotoxicity in a panel of eight diverse pancreatic cancer cell lines. Combining TSA with PS-341 effectively inactivated NF kappa B signaling, downregulated the predominant endogenous anti-apoptotic factor Bcl-XL overexpression, and disrupted MAP kinase pathway. The combined drug regimen effectively inflicted an average of 71.5% apoptotic cell death (55.2-80%) in diverse pancreatic cancer cell lines by activating the intrinsic apoptotic pathway. Conclusion: the TSA/PS-341 regimen may represent a potential novel therapeutic strategy for pancreatic cancer. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Bai, JR (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. EM jbai@bidmc.harvard.edu; mcallery@bidmc.harvard.ede RI qiao, zhixin/I-3408-2012 NR 29 TC 41 Z9 44 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 6 PY 2006 VL 348 IS 4 BP 1245 EP 1253 DI 10.1016/j.bbrc.2006.07.185 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 082ZL UT WOS:000240425600006 PM 16904634 ER PT J AU Sordella, R Van Aelst, L AF Sordella, Raffaella Van Aelst, Linda TI Driving actin dynamics under the influence of alcohol SO CELL LA English DT Editorial Material ID GTPASES AB The actin cytoskeleton plays a pivotal role in regulating neuronal development and activity, and dysregulation of actin dynamics has been linked to impaired cognitive function. In this issue of Cell, Rothenfluh et al. (2006) and Offenhauser et al. (2006) show that actin dynamics can also affect the cellular and behavioral responses of flies and mice to alcohol. C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Sordella, R (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, 13th St, Charlestown, MA 02129 USA. EM vanaelst@cshl.edu NR 7 TC 8 Z9 8 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 6 PY 2006 VL 127 IS 1 BP 37 EP 39 DI 10.1016/j.cell.2006.09.017 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 097KJ UT WOS:000241445800009 PM 17018272 ER PT J AU Cui, LB Jeong, H Borovecki, F Parkhurst, CN Tanese, N Krainc, D AF Cui, Libin Jeong, Hyunkyung Borovecki, Fran Parkhurst, Christopher N. Tanese, Naoko Krainc, Dimitri TI Transcriptional repression of PGC-alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration SO CELL LA English DT Article ID INDUCED PERMEABILITY TRANSITION; KNOCK-IN MICE; ENERGY-METABOLISM; MOUSE MODEL; GLUCOSE-METABOLISM; AXONAL-TRANSPORT; STRIATAL NEURONS; DISEASE; CREB; EXPRESSION AB Huntington's disease (HID) is an inherited neurodegenerative disease caused by a glutamine repeat expansion in huntingtin protein. Transcriptional deregulation and altered energy metabolism have been implicated in HID pathogenesis. We report here that mutant huntingtin causes disruption of mitochondrial function by inhibiting expression of PGC-1 alpha, a transcriptional coactivator that regulates several metabolic processes, including mitochondrial biogenesis and respiration. Mutant huntingtin represses PGC-1 alpha gene transcription by associating with the promoter and interfering with the CREB/TAF4-dependent transcriptional pathway critical for the regulation of PGC-1 alpha gene expression. Crossbreeding of PGC-1 alpha knockout (KO) mice with HID knockin (KI) mice leads to increased neurodegeneration of striatal neurons and motor abnormalities in the HID mice. Importantly, expression of PGC-1 alpha partially reverses the toxic effects of mutant huntingtin in cultured striatal neurons. Moreover, lentiviral-mediated delivery of PGC-1 alpha in the striatum provides neuroprotection in the transgenic HID mice. These studies suggest a key role for PGC-1 alpha in the control of energy metabolism in the early stages of HID pathogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat,Dept Neurol, Charlestown, MA 02129 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. RP Cui, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat,Dept Neurol, Charlestown, MA 02129 USA. EM krainc@helix.mgh.harvard.edu FU NINDS NIH HHS [R01NS050352, P01NS045242]; Parkinson's UK [K-1206] NR 42 TC 535 Z9 542 U1 14 U2 40 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 6 PY 2006 VL 127 IS 1 BP 59 EP 69 DI 10.1016/j.cell.2006.09.015 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 097KJ UT WOS:000241445800014 PM 17018277 ER PT J AU Khanicheh, A Muto, A Triantafyllou, C Weinberg, B Astrakas, L Tzika, A Mavroidis, C AF Khanicheh, Azadeh Muto, Andrew Triantafyllou, Christina Weinberg, Brian Astrakas, Loukas Tzika, Aria Mavroidis, Constantinos TI fMRI-compatible rehabilitation hand device SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article ID VEHICULAR INSTRUMENT CONTROLS; FLUIDIC RESISTIVE ACTUATORS; VIRTUAL-REALITY EXPERIMENTS; ELECTRORHEOLOGICAL FLUIDS; SYSTEM; FEEDBACK; FORCE; INTERVENTIONS; DESIGN AB Background: Functional magnetic resonance imaging (fMRI) has been widely used in studying human brain functions and neurorehabilitation. In order to develop complex and well-controlled fMRI paradigms, interfaces that can precisely control and measure output force and kinematics of the movements in human subjects are needed. Optimized state-of-the-art fMRI methods, combined with magnetic resonance (MR) compatible robotic devices for rehabilitation, can assist therapists to quantify, monitor, and improve physical rehabilitation. To achieve this goal, robotic or mechatronic devices with actuators and sensors need to be introduced into an MR environment. The common standard mechanical parts can not be used in MR environment and MR compatibility has been a tough hurdle for device developers. Methods: This paper presents the design, fabrication and preliminary testing of a novel, one degree of freedom, MR compatible, computer controlled, variable resistance hand device that may be used in brain MR imaging during hand grip rehabilitation. We named the device MR_ CHIROD (Magnetic Resonance Compatible Smart Hand Interfaced Rehabilitation Device). A novel feature of the device is the use of Electro-Rheological Fluids (ERFs) to achieve tunable and controllable resistive force generation. ERFs are fluids that experience dramatic changes in rheological properties, such as viscosity or yield stress, in the presence of an electric field. The device consists of four major subsystems: a) an ERF based resistive element; b) a gearbox; c) two handles and d) two sensors, one optical encoder and one force sensor, to measure the patient induced motion and force. The smart hand device is designed to resist up to 50% of the maximum level of gripping force of a human hand and be controlled in real time. Results: Laboratory tests of the device indicate that it was able to meet its design objective to resist up to approximately 50% of the maximum handgrip force. The detailed compatibility tests demonstrated that there is neither an effect from the MR environment on the ERF properties and performance of the sensors, nor significant degradation on MR images by the introduction of the MR_CHIROD in the MR scanner. Conclusion: The MR compatible hand device was built to aid in the study of brain function during generation of controllable and tunable force during handgrip exercising. The device was shown to be MR compatible. To the best of our knowledge, this is the first system that utilizes ERF in MR environment. C1 Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. Harvard Univ, Sch Med, NMR Surg Lab, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Mavroidis, C (reprint author), Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. EM azadeh@coe.neu.edu; andymuto@MIT.EDU; christin@nmr.mgh.harvard.edu; shwagg01@coe.neu.edu; lastrakas@hotmail.com; atzika@hms.harvard.edu; mavro@coe.neu.edu RI Triantafyllou, Christina/E-7724-2011; Astrakas, Loukas/F-5918-2011 NR 34 TC 26 Z9 27 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD OCT 6 PY 2006 VL 3 AR 24 DI 10.1186/1743-0003-3-24 PG 11 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 235UF UT WOS:000251259100001 PM 17022828 ER PT J AU Pan, S Wang, Y Quinn, JF Peskind, ER Waichunas, D Wimberger, JT Jin, JH Li, JG Zhu, D Pan, C Zhang, J AF Pan, Sheng Wang, Yan Quinn, Joseph F. Peskind, Elaine R. Waichunas, Dana Wimberger, Jake T. Jin, Jinghua Li, Jane G. Zhu, David Pan, Catherine Zhang, Jing TI Identification of glycoproteins in human cerebrospinal fluid with a complementary proteomic approach SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE mass spectrometry; proteomics; cerebrospinal fluid; glycoprotein; hydrazide chemistry; lectin affinity column ID TANDEM MASS-SPECTROMETRY; N-LINKED GLYCOPROTEINS; NEURODEGENERATIVE DISEASES; PROTEIN GLYCOSYLATION; BIOMARKER DISCOVERY; HYDRAZIDE CHEMISTRY; ALZHEIMERS-DISEASE; STATISTICAL-MODEL; HUMAN SERUM; DIAGNOSIS AB Biomarkers are pressingly needed to assist with the clinical diagnosis of neurodegenerative diseases and/or the monitoring of disease progression. Glycoproteins are enriched in bodily fluids such as human cerebrospinal fluid (CSF), an ideal source for discovering biomarkers due to its proximity to the central nervous system (CNS), and consequently can serve as diagnostic and/or therapeutic markers for CNS diseases. We report here an in-depth identification of glycoproteins in human CSF using a complementary proteomic approach which integrated hydrazide chemistry and lectin affinity column for glycoprotein enrichment, followed by multidimensional chromatography separation and tandem mass spectrometric analysis. Using stringent criteria, a total of 216 glycoproteins, including many low-abundance proteins, was identified with high confidence. Approximately one-third of these proteins was already known to be relevant to the CNS structurally or functionally. This investigation, for the first time, not only categorized many glycoproteins in human CSF but also expanded the existing overall CSF protein database. C1 Univ Washington, Sch Med, Div Neuropathol, Harborview Med Ctr,Dept Pathol, Seattle, WA 98104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Inst Syst Biol, Seattle, WA 98103 USA. Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. VA NW Network Mental Illness Res Educ & Clin Ctr, Va Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Div Neuropathol, Harborview Med Ctr,Dept Pathol, Box 359635, Seattle, WA 98104 USA. EM zhangj@u.washington.edu RI Jin, Jinghua/G-6385-2010 FU NIA NIH HHS [AG05136, AG08017, AG025327, AG08419]; NIEHS NIH HHS [ES012703] NR 38 TC 68 Z9 70 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT 6 PY 2006 VL 5 IS 10 BP 2769 EP 2779 DI 10.1021/pr060251s PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 091UF UT WOS:000241053100029 PM 17022648 ER PT J AU Ndassa, YM Orsi, C Marto, JA Chen, S Ross, MM AF Ndassa, Yasmine M. Orsi, Chris Marto, Jarrod A. Chen, She Ross, Mark M. TI Improved immobilized metal affinity chromatography for large-scale phosphoproteomics applications SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE immobilized metal affinity chromatography; phosphoproteomics ID TANDEM MASS-SPECTROMETRY; TYROSINE PHOSPHORYLATION SITES; LIQUID-CHROMATOGRAPHY; SACCHAROMYCES-CEREVISIAE; SIGNALING PATHWAY; HUMAN GENOME; PROTEINS; PEPTIDES; MS/MS; SEPARATION AB Dysregulated protein phosphorylation is a primary culprit in multiple physiopathological states. Hence, although analysis of signaling cascades on a proteome-wide scale would provide significant insight into both normal and aberrant cellular function, such studies are simultaneously limited by sheer biological complexity and concentration dynamic range. In principle, immobilized metal affinity chromatography (IMAC) represents an ideal enrichment method for phosphoproteomics. However, anecdotal evidence suggests that this technique is not widely and successfully applied beyond analysis of simple standards, gel bands, and targeted protein immunoprecipitations. Here, we report significant improvements in IMAC-based methodology for enrichment of phosphopeptides from complex biological mixtures. Moreover, we provide detailed explanation for key variables that in our hands most influenced the outcome of these experiments. Our results indicate 5- to 10-fold improvement in recovery of singly- and multiply phosphorylated peptide standards in addition to significant improvement in the number of high-confidence phosphopeptide sequence assignments from global analysis of cellular lysate. In addition, we quantitatively track phosphopeptide recovery as a function of phosphorylation state, and provide guidance for impedance-matching IMAC column capacity with anticipated phosphopeptide content of complex mixtures. Finally, we demonstrate that our improved methodology provides for identification of phosphopeptide distributions that closely mimic physiological conditions. C1 Harvard Univ, Dept Canc Biol, Sch Med,Biophys Program,Dept Biol Chem & Mol Phar, Dana Farber Canc Inst,Dept Biol Chem & Mol Pharma, Boston, MA 02115 USA. Natl Inst Biol Sci, Proteom Facil, Beijing 102206, Peoples R China. Univ Virginia, Mellon Med Biomarker Discovery Lab, Charlottesville, VA USA. RP Marto, JA (reprint author), Harvard Univ, Dept Canc Biol, Sch Med,Biophys Program,Dept Biol Chem & Mol Phar, Dana Farber Canc Inst,Dept Biol Chem & Mol Pharma, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu NR 32 TC 90 Z9 90 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT 6 PY 2006 VL 5 IS 10 BP 2789 EP 2799 DI 10.1021/pr0602803 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 091UF UT WOS:000241053100031 PM 17022650 ER PT J AU Neale, B Asherson, P Purcell, S Brookes, K Zhou, KX Chen, W Buitelaar, J Ebstein, RS Gill, M Banaschewski, T Manor, I Miranda, A Oades, B Roeyers, H Rothenberger, A Sergeant, J Steinhausen, HC Sonuga-Barke, EJS Sham, P Faraone, S AF Ben Neale Asherson, Philip Purcell, Shaun Brookes, Keeley Zhou, Kaixin Chen, Wai Buitelaar, Jan Ebstein, Richard S. Gill, Michael Banaschewski, Tobias Manor, Iris Miranda, Ana Oades, Bob Roeyers, Herbert Rothenberger, Ari Sergeant, Jo Steinhausen, Hans-Christoph Sonuga-Barke, Edmund J. S. Sham, Pak Faraone, Steve TI An examination of population differences in the image sample across 47 autosomal genes implicated in psychiatric disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Inst Psychiat, London, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands. Herzog Mem Hosp, Jerusalem, Israel. Trinity Ctr Hlth Sci, Dublin, Ireland. Univ Gottingen, D-3400 Gottingen, Germany. Geha MHC, Tel Aviv, Israel. Univ Valencia, Valencia, Spain. Univ Essen Gesamthsch, Clin Child & Adolescents, Essen, Germany. Univ Ghent, B-9000 Ghent, Belgium. Univ Amsterdam, Amsterdam, Netherlands. Univ Zurich, Zurich, Switzerland. Univ Southampton, Southampton SO9 5NH, Hants, England. SUNY Upstate Med Univ, Syracuse, NY USA. RI Sonuga-Barke, Edmund/D-9137-2011; Buitelaar, Jan/E-4584-2012; Miranda, Ana/G-8619-2015 OI Buitelaar, Jan/0000-0001-8288-7757; Miranda, Ana/0000-0001-6998-5686 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O171 BP 719 EP 719 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700153 ER PT J AU Smoller, J Fagerness, J Purcell, S Yamaki, L Watras, L Biederman, J Sklar, P Rosenbaum, J AF Smoller, Jordan Fagerness, Jes Purcell, Shaun Yamaki, Lesley Watras, Lisa Biederman, Joseph Sklar, Pamela Rosenbaum, Jerrold TI Rgs2, the human ortholog of a mouse anxiety gene, is associated with anxious temperament SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O226 BP 725 EP 725 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700183 ER PT J AU Santangelo, S Haddad, S Santos, T Fagerness, J Moilanen, I Mattila, ML Jussila, K Kuusikko, S Ignatius, J Yamaki, L Moorjani, P Pauls, D Ramesh, V AF Santangelo, Susan Haddad, Stephen Santos, Tulio Fagerness, Jesen Moilanen, Irma Mattila, Marja-Leena Jussila, Katja Kuusikko, Sanna Ignatius, Jaakko Yamaki, Lesley Moorjani, Priya Pauls, David Ramesh, Vijaya TI Pam as a candidate gene for autism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. CHGR, Psychiat Neurodev Genet Unit, Boston, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. Univ Oulu, Dept Child Psychiat, FIN-90570 Oulu, Finland. Univ Oulu, Genet Lab, FIN-90570 Oulu, Finland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 735 EP 736 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700229 ER PT J AU Montet, X Funovics, M Montet-Abou, K Weissleder, R Josephson, L AF Montet, Xavier Funovics, Martin Montet-Abou, Karin Weissleder, Ralph Josephson, Lee TI Multivalent effects of RGD peptides obtained by nanoparticle display SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CYCLIC PENTAPEPTIDES; INTEGRINS; TUMOR; VITRONECTIN; RECEPTORS; BIODISTRIBUTION; INHIBITORS; BINDING; DESIGN; NEOVASCULATURE AB The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE = IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V) beta(3) function on endothelial cells in vivo. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Vienna Med Univ, Dept Angiog & Intervent Radiol, Vienna, Austria. Geneva Hosp, Dept Radiol, Geneva, Switzerland. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. EM ljosephson@partners.org OI Montet, Xavier/0000-0003-2442-5866 FU NCI NIH HHS [P50 CA86355, R24 CA92782]; NIBIB NIH HHS [R01 EB00662] NR 40 TC 225 Z9 228 U1 5 U2 48 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 OCT 5 PY 2006 VL 49 IS 20 BP 6087 EP 6093 DI 10.1021/jm060515m PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 088QM UT WOS:000240826200023 PM 17004722 ER PT J AU Storchova, Z Breneman, A Cande, J Dunn, J Burbank, K O'Toole, E Pellman, D AF Storchova, Zuzana Breneman, Amanda Cande, Jessica Dunn, Joshua Burbank, Kendra O'Toole, Eileen Pellman, David TI Genome-wide genetic analysis of polyploidy in yeast SO NATURE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; BI-ORIENTATION; SISTER CHROMATIDS; MITOTIC SPINDLE; BUDDING YEAST; RECOMBINATION; PROTEIN; EVOLUTION; TENSION; KINASE AB Polyploidy, increased sets of chromosomes, occurs during development, cellular stress, disease and evolution. Despite its prevalence, little is known about the physiological alterations that accompany polyploidy. We previously described 'ploidy-specific lethality', where a gene deletion that is not lethal in haploid or diploid budding yeast causes lethality in triploids or tetraploids. Here we report a genome-wide screen to identify ploidy-specific lethal functions. Only 39 out of 3,740 mutations screened exhibited ploidy-specific lethality. Almost all of these mutations affect genomic stability by impairing homologous recombination, sister chromatid cohesion, or mitotic spindle function. We uncovered defects in wild-type tetraploids predicted by the screen, and identified mechanisms by which tetraploidization affects genomic stability. We show that tetraploids have a high incidence of syntelic/monopolar kinetochore attachments to the spindle pole. We suggest that this defect can be explained by mismatches in the ability to scale the size of the spindle pole body, spindle and kinetochores. Thus, geometric constraints may have profound effects on genome stability; the phenomenon described here may be relevant in a variety of biological contexts, including disease states such as cancer. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Phys, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Hematol Oncol, Childrens Hosp, Boston, MA 02115 USA. Univ Colorado, Boulder Lab 3D Elect Microscopy Cells, Boulder, CO 80309 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu OI Dunn, Joshua/0000-0003-4476-7257 NR 47 TC 173 Z9 180 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 5 PY 2006 VL 443 IS 7111 BP 541 EP 547 DI 10.1038/nature05178 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 090XO UT WOS:000240988200036 PM 17024086 ER PT J AU List, A Dewald, G Bennett, J Giagounidis, A Raza, A Feldman, E Powell, B Greenberg, P Thomas, D Stone, R Reeder, C Wride, K Patin, J Schmidt, M Zeldis, J Knight, R AF List, Alan Dewald, Gordon Bennett, John Giagounidis, Aristotle Raza, Azra Feldman, Eric Powell, Bayard Greenberg, Peter Thomas, Deborah Stone, Richard Reeder, Craig Wride, Kenton Patin, John Schmidt, Michele Zeldis, Jerome Knight, Robert CA Myelodysplastic Syndrome-003 TI Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYELOID-LEUKEMIA; LONG ARM; CLASSIFICATION; PROGNOSIS; CRITERIA; LIFE AB Background: Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31- clone in patients with this disorder. Methods: One hundred forty-eight patients received 10 mg of lenalidomide for 21 days every 4 weeks or daily. Hematologic, bone marrow, and cytogenetic changes were assessed after 24 weeks of treatment by an intention-to-treat analysis. Results: Among the 148 patients, 112 had a reduced need for transfusions (76%; 95% confidence interval [CI], 68 to 82) and 99 patients (67%; 95% CI, 59 to 74) no longer required transfusions, regardless of the karyotype complexity. The response to lenalidomide was rapid (median time to response, 4.6 weeks; range, 1 to 49) and sustained; the median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. The maximum hemoglobin concentration reached a median of 13.4 g per deciliter (range, 9.2 to 18.6), with a corresponding median rise of 5.4 g per deciliter (range, 1.1 to 11.4), as compared with the baseline nadir value before transfusion. Among 85 patients who could be evaluated, 62 had cytogenetic improvement, and 38 of the 62 had a complete cytogenetic remission. There was complete resolution of cytologic abnormalities in 38 of 106 patients whose serial bone marrow samples could be evaluated. Moderate-to-severe neutropenia (in 55% of patients) and thrombocytopenia (in 44%) were the most common reasons for interrupting treatment or adjusting the dose of lenalidomide. Conclusions: Lenalidomide can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients who have the myelodysplastic syndrome with the 5q31 deletion. (ClinicalTrials.gov number, NCT00065156.) C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Malignant Hematol Div, Tampa, FL 33612 USA. Mayo Clin, Rochester, MN USA. Univ Rochester, Rochester, NY USA. St Johannes Hosp, Duisburg, Germany. Univ Massachusetts, Worcester, MA 01605 USA. Cornell Med Ctr, New York, NY USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Scottsdale, AZ USA. Celgene Corp, Warren, NJ USA. RP List, A (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Malignant Hematol Div, SRB-4,12902 Magnolia Dr, Tampa, FL 33612 USA. EM heberten@moffitt.usf.edu NR 18 TC 641 Z9 665 U1 0 U2 8 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 OCT 5 PY 2006 VL 355 IS 14 BP 1456 EP 1465 DI 10.1056/NEJMoa061292 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 090UA UT WOS:000240976200007 PM 17021321 ER PT J AU Macip, S Kosoy, A Lee, SW O'Connell, MJ Aaronson, SA AF Macip, S. Kosoy, A. Lee, S. W. O'Connell, M. J. Aaronson, S. A. TI Oxidative stress induces a prolonged but reversible arrest in p53-null cancer cells, involving a Chk1-dependent G(2) checkpoint SO ONCOGENE LA English DT Article DE senescence; p53; ROS; Chk1; checkpoints ID DNA-DAMAGE CHECKPOINT; LACKING FUNCTIONAL P53; STRAND BREAK REPAIR; HUMAN FIBROBLASTS; TUMOR-CELLS; REPLICATIVE SENESCENCE; GROWTH ARREST; IN-VIVO; PREMATURE SENESCENCE; CELLULAR SENESCENCE AB Reactive oxygen species (ROS), the principal mediators of oxidative stress, induce responses suchas apoptosis or permanent growth arrest/senescence in normal cells. Moreover, p53 activation itself contributes to ROS accumulation. Here we show that treatment of p53-null cancer cells with sublethal concentrations of ROS triggered an arrest with some morphological similarities to cellular senescence. Different from a classical senescent arrest in G(1), the ROS-induced arrest was predominantly in the G(2) phase of the cell cycle, and its establishment depended at least in part on an intact Chk1-dependent checkpoint. Chk1 remained phosphorylated only during the repair of double strand DNA breaks, after which Chk1 was inactivated, the G2 arrest was suppressed, and some cells recovered their ability to proliferate. Inhibition of Chk1 by an RNAi approach resulted in an increase in cell death in p53-null cells, showing that the Chk1-dependent G2 checkpoint protected cells that lacked a functional p53 pathway from oxidative stress. It has been proposed that the induction of a senescent-like phenotype by antineoplastic agents can contribute therapeutic efficacy. Our results indicate that oxidative stress-induced growth arrest of p53-null tumor cells cannot be equated with effective therapy owing to its reversibility and supports the concept that targeting Chk1 may enhance the effects of DNA-damaging agents on cancer progression in such tumors. C1 Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Aaronson, SA (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM stuart.aaronson@mssm.edu RI Macip, Salvador/K-5985-2014 FU NCI NIH HHS [CA100076, CA85214, CA82211, CA78356, CA80058] NR 81 TC 21 Z9 21 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 5 PY 2006 VL 25 IS 45 BP 6037 EP 6047 DI 10.1038/sj.onc.1209629 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 092MN UT WOS:000241101200001 PM 16652144 ER PT J AU Kim, WY Safran, M Buckley, MRM Ebert, BL Glickman, J Bosenberg, M Regan, M Kaelin, WG AF Kim, William Y. Safran, Michal Buckley, Marshall R. M. Ebert, Benjamin L. Glickman, Jonathan Bosenberg, Marcus Regan, Meredith Kaelin, William G., Jr. TI Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo SO EMBO JOURNAL LA English DT Article DE hypoxia-inducible factor; prolyl hydroxylase; von Hippel-Lindau ID LINDAU TUMOR-SUPPRESSOR; RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; TRANSCRIPTION FACTOR; VASCULAR TUMORS; CHUVASH POLYCYTHEMIA; HIF HYDROXYLASES; FACTOR 1-ALPHA; MESSENGER-RNA; CYCLIN D1 AB Many functions have been assigned to the von Hippel-Lindau tumor suppressor gene product (pVHL), including targeting the alpha subunits of the heterodimeric transcription factor HIF (hypoxia-inducible factor) for destruction. The binding of pVHL to HIF alpha requires that HIFa be hydroxylated on one of two prolyl residues. We introduced HIF1 alpha and HIF2 alpha variants that cannot be hydroxylated on these sites into the ubiquitously expressed ROSA26 locus along with a Lox-stop-Lox cassette that renders their expression Cre-dependent. Expression of the HIF2a variant in the skin and liver induced changes that were highly similar to those seen when pVHL is lost in these organs. Dual expression of the HIF1a and HIF2a variants in liver, however, more closely phenocopied the changes seen after pVHL inactivation than did the HIF2a variant alone. Moreover, gene expression profiling confirmed that the genes regulated by HIF1a and HIF2a in the liver are overlapping but non- identical. Therefore, the pathological changes caused by pVHL inactivation in skin and liver are due largely to dysregulation of HIF target genes. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. MIT, Broad Inst, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02215 USA. Univ Vermont, Dept Pathol, Burlington, VT USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St,Mayer 457, Boston, MA 02215 USA. EM William_kaelin@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 56 TC 121 Z9 122 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 4 PY 2006 VL 25 IS 19 BP 4650 EP 4662 DI 10.1038/sj.embroj.7601300 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 092DU UT WOS:000241078000023 PM 16977322 ER PT J AU Celone, KA Calhoun, VD Dickerson, BC Atri, A Chua, EF Miller, SL DePeau, K Rentz, DM Selkoe, DJ Blacker, D Albert, MS Sperling, RA AF Celone, Kim A. Calhoun, Vince D. Dickerson, Bradford C. Atri, Alireza Chua, Elizabeth F. Miller, Saul L. DePeau, Kristina Rentz, Doreen M. Selkoe, Dennis J. Blacker, Deborah Albert, Marilyn S. Sperling, Reisa A. TI Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: An independent component analysis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; mild cognitive impairment; fMRI; hippocampus; default mode network; independent component analyses ID FUNCTIONAL MRI; HIPPOCAMPAL-FORMATION; DEFAULT-MODE; FMRI; BRAIN; ACTIVATION; AD; RISK; TASK; DEACTIVATIONS AB Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease ( AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Memory Disorders Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. Hartford Hosp, Inst Living, Olin Neuropsychoat Res Ctr, Hartford, CT 06106 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Sperling, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Memory Disorders Unit, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu RI Chua, Elizabeth/B-3770-2010; Calhoun, Vince/H-7146-2013; OI Calhoun, Vince/0000-0001-9058-0747; Atri, Alireza/0000-0003-4405-6973 FU NCRR NIH HHS [P41-RR14075]; NIA NIH HHS [P01-AG04953, P50-AG05134]; NINDS NIH HHS [K23-NS02189] NR 46 TC 371 Z9 384 U1 4 U2 46 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 OCT 4 PY 2006 VL 26 IS 40 BP 10222 EP 10231 DI 10.1523/JNEUROSCI.2250-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 093TN UT WOS:000241192700015 PM 17021177 ER PT J AU Hurley, KM Gaboyard, S Zhong, M Price, SD Wooltorton, JRA Lysakowski, A Eatock, RA AF Hurley, Karen M. Gaboyard, Sophie Zhong, Meng Price, Steven D. Wooltorton, Julian R. A. Lysakowski, Anna Eatock, Ruth Anne TI M-like K+ currents in type I hair cells and calyx afferent endings of the developing rat utricle SO JOURNAL OF NEUROSCIENCE LA English DT Article DE vestibular; KCNQ channels; erg channels; development; hair cells; M current ID VESTIBULAR END ORGANS; POTASSIUM CHANNELS; DELAYED RECTIFIER; IONIC CURRENTS; INNER-EAR; DOMINANT DEAFNESS; NG108-15 CELLS; MOUSE UTRICLE; NITRIC-OXIDE; EXPRESSION AB Type I vestibular hair cells have large K+ currents that, like neuronal M currents, activate negative to resting potential and are modulatable. In rodents, these currents are acquired postnatally. In perforated-patch recordings from rat utricular hair cells, immature hair cells [younger than postnatal day 7 (P7)] had a steady-state K+ conductance (g(-30)) with a half-activation voltage (V-1/ 2) of -30 mV. The size and activation range did not change in maturing type II cells, but, by P16, type I cells had added a K conductance that was on average fourfold larger and activated much more negatively. This conductance may comprise two components: g(-60) (V-1/2 of -60 mV) and g(-80) (V-1/ 2 of -80 mV). g(-80) washed out during ruptured patch recordings and was blocked by a protein kinase inhibitor. M currents can include contributions from KCNQ and ether-a-go-go-related (erg) channels. KCNQ and erg channel blockers both affected the K+ currents of type I cells, with KCNQ blockers being more potent at younger than P7 and erg blockers more potent at older than P16. Single-cell reverse transcription-PCR and immunocytochemistry showed expression of KCNQ and erg subunits. We propose that KCNQ channels contribute to g(-30) and g-(60) and erg subunits contribute to g(-80). Type I hair cells are contacted by calyceal afferent endings. Recordings from dissociated calyces and afferent endings revealed large K+ conductances, including a KCNQ conductance. Calyx endings were strongly labeled by KCNQ4 and erg1 antisera. Thus, both hair cells and calyx endings have large M-like K+ conductances with the potential to control the gain of transmission. C1 Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA. Baylor Coll Med, Bobby R Alford Dept Otorhinolaryngol Head Neck S, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Eatock, RA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM eatock@meei.harvard.edu RI Lysakowski, Anna/F-9534-2010; yu, yan/C-2322-2012; Eatock, Ruth/F-6404-2013; OI Lysakowski, Anna/0000-0001-6259-0294; Eatock, Ruth Anne/0000-0001-7547-2051; Wooltorton, Julian/0000-0003-0778-0196; Gaboyard-Niay, Sophie/0000-0001-8256-8692 FU NIDCD NIH HHS [DC002290, R01 DC002290] NR 65 TC 52 Z9 52 U1 0 U2 0 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 OCT 4 PY 2006 VL 26 IS 40 BP 10253 EP 10269 DI 10.1523/JNEUROSCI.2596-06.2006 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 093TN UT WOS:000241192700019 PM 17021181 ER PT J AU Maison, SF Rosahl, TW Homanics, GE Liberman, MC AF Maison, Stephane F. Rosahl, Thomas W. Homanics, Gregg E. Liberman, M. Charles TI Functional role of GABAergic innervation of the cochlea: Phenotypic analysis of mice lacking GABA(A) receptor subunits alpha 1, alpha 2, alpha 5, alpha 6, alpha 2, alpha 3, or delta SO JOURNAL OF NEUROSCIENCE LA English DT Article DE efferent; hair cell; olivocochlear; auditory; feedback; knock-out mice ID OUTER HAIR-CELLS; SPIRAL GANGLION NEURONS; GAMMA-AMINOBUTYRIC-ACID; INDUCED HEARING-LOSS; GUINEA-PIG COCHLEA; PRODUCT OTOACOUSTIC EMISSIONS; IN-SITU HYBRIDIZATION; ACOUSTIC INJURY; BRAIN-STEM; ELECTRICAL-STIMULATION AB The olivocochlear efferent system is both cholinergic and GABAergic and innervates sensory cells and sensory neurons of the inner ear. Cholinergic effects on cochlear sensory cells are well characterized, both in vivo and in vitro; however, the robust GABAergic innervation is poorly understood. To explore the functional roles of GABA in the inner ear, we characterized the cochlear phenotype of seven mouse lines with targeted deletion of a GABA(A) receptor subunit (alpha 1, alpha 2, alpha 5, alpha 6, beta 2, beta 3, or delta). Four of the lines (alpha 1, alpha 2, alpha 6, and delta) were normal: there was no cochlear histopathology, and cochlear responses suggested normal function of hair cells, afferent fibers, and efferent feedback. The other three lines (alpha 5, beta 2, and beta 3) showed threshold elevations indicative of outer hair cell dysfunction. alpha 5 and beta 2 lines also showed decreased effects of efferent bundle activation, associated with decreased density of efferent terminals on outer hair cells: although the onset of this degeneration was later in alpha 5 (> 6 weeks) than beta 2 (< 6 weeks), both lines shows normal efferent development (up to 3 weeks). Two lines (beta 2 and beta 3) showed signs of neuropathy, either decreased density of afferent innervation (beta 3) or decreased neural responses without concomitant attenuation of hair cell responses (beta 2). One of the lines (beta 2) showed a clear sexual dimorphism in cochlear phenotype. Results suggest that the GABAergic component of the olivocochlear system contributes to the long-term maintenance of hair cells and neurons in the inner ear. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol, Boston, MA 02114 USA. Merck Sharp & Dohme Ltd, Res Labs, Ctr Res Neurosci, Harlow CM20 2QR, Essex, England. Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15260 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM stephane_maison@meei.harvard.edu FU NIDCD NIH HHS [P30 DC 005029, P30 DC005209, R01 DC 00188, R01 DC000188] NR 76 TC 40 Z9 40 U1 0 U2 7 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 OCT 4 PY 2006 VL 26 IS 40 BP 10315 EP 10326 DI 10.1523/JNEUROSCI.2395-06.2006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 093TN UT WOS:000241192700025 PM 17021187 ER PT J AU Kawate, T Wang, BH Allerson, CR Wolfe, JL AF Kawate, Tomohiko Wang, Bing H. Allerson, Charles R. Wolfe, Jia Liu TI Synthesis and application of nitro-substituted nucleosides and nucleotides SO SYNTHESIS-STUTTGART LA English DT Article DE cleavage; nucleotides; oligonucleotides; nucleophilic additions; regioselectivity ID ACID RELATED-COMPOUNDS; REGIOSELECTIVE SYNTHESES; DNA; CONTACTS; SEQUENCE; UTILITY AB Protocols for the synthesis of C-7-nitropurine nucleosides and nucleotides are described. Each of these nucleotides can completely replace its naturally occurring counterpart in polymerase chain reaction (PCR), generating amplified duplex DNA containing nitropurines. As predicted, the electron-withdrawing power of the nitro group rendered these modified oligonucleotides susceptible to chemoselective cleavage at the modified bases. Treatment with secondary amines at elevated temperatures produced selective DNA scission at nitropurine sites. Interestingly, this Maxam-Gilbert type of DNA cleavage reaction was facilitated by the addition of tris(2-carboxyethyl)phosphine (TCEP), a strong reducing agent and nucleophile. Mass spectrometry analysis not only confirmed that DNA cleavage occurred at the nitropurines, but also revealed that the fragmented DNA products are appended by a TCEP moiety at its 3 '-end. This surprising result provided new insights into the mechanisms of such DNA cleavage reactions. C1 Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Wolfe, JL (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM jwolfe@ccib.mgh.harvard.edu NR 24 TC 1 Z9 1 U1 1 U2 5 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0039-7881 J9 SYNTHESIS-STUTTGART JI Synthesis PD OCT 4 PY 2006 IS 19 BP 3280 EP 3290 DI 10.1055/s-2006-950218 PG 11 WC Chemistry, Organic SC Chemistry GA 099WJ UT WOS:000241627600015 ER PT J AU Dobscha, SK Corson, K Hickam, DH Perrin, NA Kraemer, DF Gerrity, MS AF Dobscha, Steven K. Corson, Kathryn Hickam, David H. Perrin, Nancy A. Kraemer, Dale F. Gerrity, Martha S. TI Depression decision support in primary care - A cluster randomized trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COMORBID MEDICAL ILLNESS; IMPROVING PRIMARY-CARE; MANAGED PRIMARY-CARE; COLLABORATIVE CARE; MAJOR DEPRESSION; TREATMENT GUIDELINES; OUTCOMES; DISORDERS; EDUCATION; IMPACT AB Background: Intensive collaborative interventions improve depression outcomes, but the benefit of less intensive interventions is not clear. Objective: To determine whether decision support improves outcomes for patients with depression. Design: Clinician-level, cluster randomized, controlled trial. Setting: 5 primary care clinics of 1 Veterans Affairs medical center. Participants: 41 primary care clinicians, and 375 patients with depression (Patient Health Questionnaire [PHQ-9] depression scores of 10 to 25 or Hopkins Symptom Checklist-20 [SCL-20] scores >= 1.0). Measurements: The primary outcome was change in depression score (SCL-20) at 6 and 12 months. Secondary outcomes were health-related quality-of-life (36-item Short Form for Veterans [SF-36V] score), patient satisfaction, antidepressant use, and health care utilization. Intervention: Clinicians received depression education and were randomly assigned to depression decision support or usual care. The depression decision support team, which consisted of a psychiatrist and nurse, provided 1 early patient educational contact and depression monitoring with feedback to clinicians over 12 months. Results: Although SCL-20 depression scores improved in both groups, the intervention had no effect compared with usual care. The difference in slopes comparing intervention and control over 12 months was 0.20 (95% Cl, -0.37 to 0.78; P = 0.49), which was neither clinically nor statistically significant. Changes in SF-36V scores also did not differ between groups. At 12 months, intervention patients reported greater satisfaction (P = 0.002) and were more likely to have had at least 1 mental health specialty appointment (41.1 % vs. 27.2%; P = 0.025), to have received any antidepressant (79.3% vs. 69.3%; P = 0.041), and to have received antidepressants for 90 days or more (76.2% vs. 61.6%; P 0.008). Limitations: Usual care clinicians received depression education and had on-site mental health support, which may have mitigated intervention effectiveness. Conclusions: Decision support improved processes of care but not depression outcomes. More intensive care management or specialty treatment may be needed to improve depression outcomes. C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Oregon State Univ, Portland, OR USA. RP Dobscha, SK (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, POB 1034 P3MHDC, Portland, OR 97207 USA. EM steven.dobscha@va.gov NR 64 TC 48 Z9 49 U1 4 U2 10 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 OCT 3 PY 2006 VL 145 IS 7 BP 477 EP 487 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 092JX UT WOS:000241093900001 PM 17015865 ER PT J AU Harris, KM Sponsel, A Hutter, AM Maron, BJ AF Harris, Kevin M. Sponsel, Austin Hutter, Adolph M., Jr. Maron, Barry J. TI Cardiovascular screening practices of major North American professional sports teams SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SUDDEN CARDIAC DEATH; LEAGUE BASEBALL TEAM; HIGH-SCHOOL; HYPERTROPHIC CARDIOMYOPATHY; HEART-ASSOCIATION; FOOTBALL PLAYERS; YOUNG; DISEASE; RECOMMENDATIONS; REHABILITATION AB Background: Customary preparticipation screening strategies to detect heart disease in professional athletes have not been examined systematically. Objective: To describe the current preparticipation cardiovascular screening process for professional athletes. Design: Screening practices surveyed by questionnaire. Setting: The 122 major professional sports teams in North America. Participants: Athletic trainers and team physicians. Measurements: League recommendations for history taking and physical examination and noninvasive testing were compared with screening recommendations from an American Heart Association consensus panel. Results: All 122 teams have team physicians perform annual screening, including family and personal history taking (100%), physical examination (100%), and lipid panels (108 of 122 [89%]). Diagnostic testing by using electrocardiography was substantially more common (112 of 122 [92%]) than exercise testing and stress echocardiography (21 of 122 [17%]) or echocardiography (16 of 122 [13%]). League recommendations for history taking and physical examination were most complete for Major League Baseball and the National Hockey League, meeting 10 of 12 and 8 of 12 American Heart Association recommendations, respectively. The most comprehensive cardiovascular screening using echocardiography is confined to selected, elite professional basketball players. Limitations: Data were self-reported by team representatives. Conclusions: A variety of nonstandardized preparticipation screening strategies for the detection of cardiovascular disease, varying considerably in scope, constitute customary practice among professional sports teams. C1 Minnesota Heart Inst Fdn, Minneapolis, MN 55407 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Harris, KM (reprint author), Minnesota Heart Inst Fdn, 920 E 28th St,Suite 60, Minneapolis, MN 55407 USA. EM kharris@mplsheart.com NR 28 TC 40 Z9 40 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 3 PY 2006 VL 145 IS 7 BP 507 EP 511 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 092JX UT WOS:000241093900004 PM 17015868 ER PT J AU Rubenstein, LV AF Rubenstein, Lisa V. TI Improving care for depression: There's no free lunch SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; COST-EFFECTIVENESS; COLLABORATIVE CARE; MANAGEMENT; QUALITY; BENEFIT; IMPACT C1 VA Greater Los Angeles, Healthcare Syst, North Hills, CA 91343 USA. RAND Corp, Hlth Program, Santa Monica, CA 90406 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 91343 USA. RP Rubenstein, LV (reprint author), VA Greater Los Angeles, Healthcare Syst, 16111 Plummer St 152, North Hills, CA 91343 USA. NR 21 TC 10 Z9 12 U1 4 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 3 PY 2006 VL 145 IS 7 BP 544 EP 546 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 092JX UT WOS:000241093900009 PM 17015873 ER PT J AU Nahrendorf, M Jaffer, FA Kelly, KA Sosnovik, DE Aikawa, E Libby, P Weissleder, R AF Nahrendorf, Matthias Jaffer, Farouc A. Kelly, Kimberly A. Sosnovik, David E. Aikawa, Elena Libby, Peter Weissleder, Ralph TI Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; cell adhesion molecules; imaging; inflammation; magnetic resonance imaging ID IN-VIVO; IRON-OXIDE; MAGNETIC NANOPARTICLES; COLORECTAL-CANCER; LESION FORMATION; DEFICIENT MOUSE; RABBIT ATHEROMA; TRANSGENIC MICE; E-SELECTIN; EXPRESSION AB Background-Noninvasive imaging of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) may identify early stages of inflammation in atherosclerosis. We hypothesized that a novel, second-generation VCAM-1 targeted agent with enhanced affinity had sufficient sensitivity to enable real-time detection of VCAM-1 expression in experimental atherosclerosis in vivo, to quantify pharmacotherapy-induced reductions in VCAM-1 expression, and to identify activated cells in human plaques. Methods and Results-In vivo phage display in apolipoprotein E-deficient mice identified a linear peptide affinity ligand, VHPKQHR, homologous to very late antigen-4, a known ligand for VCAM-1. This peptide was developed into a multivalent agent detectable by MRI and optical imaging (denoted VINP- 28 for VCAM-1 internalizing nanoparticle 28, with 20 times higher affinity than previously reported for VNP). In vitro, VINP- 28 targeted all cell types expressing VCAM-1. In vivo, MRI and optical imaging in apolipoprotein E-deficient mice (n=28) after injection with VINP- 28 or saline revealed signal enhancement in the aortic root of mice receiving VINP-28 (P < 0.05). VINP-28 colocalized with endothelial cells and other VCAM-1-expressing cells, eg, macrophages, and was spatially distinct compared with untargeted control nanoparticles. Atheromata of atorvastatin-treated mice showed reduced VINP- 28 deposition and VCAM-1 expression. VINP- 28 enhanced early lesions in juvenile mice and resected human carotid artery plaques. Conclusions-VINP-28 allows noninvasive imaging of VCAM-1-expressing endothelial cells and macrophages in atherosclerosis and spatial monitoring of anti-VCAM-1 pharmacotherapy in vivo and identifies inflammatory cells in human atheromata. This clinically translatable agent could noninvasively detect inflammation in early, subclinical atherosclerosis. C1 Massachusetts Gen Hosp, CMIR, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, CMIR, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM fjaffer@partners.org; Weissleder@helix.mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NHLBI NIH HHS [R01-HL078641, R01-HL36436, U01-HL080731]; NIAID NIH HHS [P01-AI054904] NR 42 TC 336 Z9 346 U1 7 U2 43 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 3 PY 2006 VL 114 IS 14 BP 1504 EP 1511 DI 10.1161/CIRCULATIONAHA.106.646380 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 090MD UT WOS:000240954500014 PM 17000904 ER PT J AU Aplin, AC Gelati, M Fogel, E Carnevale, E Nicosia, RF AF Aplin, Alfred C. Gelati, Maurizio Fogel, Eric Carnevale, Edvige Nicosia, Roberto F. TI Angiopoietin-1 and vascular endothelial growth factor induce expression of inflammatory cytokines before angiogenesis SO PHYSIOLOGICAL GENOMICS LA English DT Article DE aorta; oligonucleotide microarray; gene profiling ID SMOOTH-MUSCLE-CELLS; TOLL-LIKE RECEPTORS; IN-VITRO; GENE-EXPRESSION; RAT AORTA; VESSEL FORMATION; INNATE IMMUNITY; TIE2 RECEPTOR; VEGF; MIGRATION AB The purpose of this study was to identify novel transcriptional events occurring in the aortic wall before angiogenesis. We used a defined tissue culture system that takes advantage of the capacity of rat aortic rings to generate neovessels ex vivo in response to angiogenic factor stimulation. Total RNA isolated from aortic rings 18 h posttreatment with angiopoietin (Ang)-1 or vascular endothelial growth factor (VEGF) was used to probe oligonucleotide microarrays. Many genes were up- or downregulated by either Ang-1 or VEGF, with a subset being affected by treatment with both growth factors. Grouping of genes by biological function revealed that Ang-1 and VEGF both upregulated a host of immune-related genes including many inflammatory cytokines. A mixture of the Ang-1- and VEGF-induced cytokines stimulated the spontaneous angiogenic response of aortic rings and was synergistic with a low dose of recombinant VEGF. This effect was associated with enhanced recruitment of adventitial macrophages and dendritic cells in the angiogenic outgrowths. Thus Ang-1 and VEGF activate the innate immune system of the vessel wall, stimulating the production of proangiogenic inflammatory cytokines before the emergence of neovessels. This hitherto unreported feature of the angiogenic response might represent an important early component of the cellular and molecular cascade responsible for the angiogenic response of the aortic wall. C1 VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S113, Seattle, WA 98108 USA. Carlo Besta Inst, Lab Neurobiol & Neuroregenerat Med, Milan, Italy. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@va.gov RI Gelati, Maurizio/H-2110-2016 OI Gelati, Maurizio/0000-0002-4828-9849 FU NHLBI NIH HHS [HL-52585, HL-072370] NR 59 TC 40 Z9 43 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD OCT 3 PY 2006 VL 27 IS 1 BP 20 EP 28 DI 10.1152/physiolgenomics.00048.2006 PG 9 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 090XJ UT WOS:000240987500003 PM 17018690 ER PT J AU Glait, C Ravid, D Lee, SW Liscovitch, M Werner, H AF Glait, Chen Ravid, Dana Lee, Sam W. Liscovitch, Mordechai Werner, Haim TI Caveolin-1 controls BRCA1 gene expression and cellular localization in human breast cancer cells SO FEBS LETTERS LA English DT Article DE caveolin-1; Caveolae; BRCA1; gene expression; breast cancer ID OVARIAN-CANCER; IN-VIVO; SUBCELLULAR-LOCALIZATION; SUSCEPTIBILITY GENE; PROTEIN EXPRESSION; PROSTATE-CANCER; NUCLEAR EXPORT; GROWTH; MUTATIONS; MEMBRANE AB The role of caveolae and the caveolin proteins in cancer has been the subject of extensive research. BRCA1 participates in multiple biological pathways including DNA damage repair, transcriptional control, cell growth, apoptosis, and others. Little information, however, is available regarding the cellular mechanisms that control BRCA1 gene expression. The present study examined the potential regulation of BRCA1 gene expression and subcellular localization by Cav-1. Results of Western blots, RT-PCR, and transfection experiments showed that Cav-1 enhances BRCA1 protein and mRNA levels via a mechanism that involves transactivation of the BRCA1 promoter and which is p53-dependent. In addition, immunostaining experiments demonstrate that Cav-1 induced the cytoplasmic sequestration of BRCA1 (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. RP Werner, H (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. EM hwerner@post.tau.ac.il NR 49 TC 14 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 2 PY 2006 VL 580 IS 22 BP 5268 EP 5274 DI 10.1016/j.febslet.2006.08.071 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 091QW UT WOS:000241044400026 PM 16979166 ER PT J AU Freeman, GJ Wherry, EJ Ahmed, R Sharpe, AH AF Freeman, Gordon J. Wherry, E. John Ahmed, Rafi Sharpe, Arlene H. TI Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID PLASMACYTOID DENDRITIC CELLS; CHRONIC VIRAL-INFECTION; IMMUNE EVASION; ACTIVATION; B7-H1; EXPRESSION; FAMILY; PD-1; PROLIFERATION; MACROPHAGES C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, 44 Binney St, Boston, MA 02115 USA. EM gordon_freeman@dfci.harvard.edu FU NIAID NIH HHS [AI56299, P01 AI056299] NR 28 TC 235 Z9 247 U1 0 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2006 VL 203 IS 10 BP 2223 EP 2227 DI 10.1084/jem.20061800 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 090KY UT WOS:000240951400008 PM 17000870 ER PT J AU Duarte, A Hayasaka, S Du, AT Schuff, N Jahng, GH Kramer, J Miller, B Weiner, M AF Duarte, Audrey Hayasaka, Satoru Du, Antao Schuff, Norbert Jahng, Geon-Ho Kramer, Joel Miller, Bruce Weiner, Michael TI Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE mild cognitive impairment; Alzheimer's; correlation; volumetry; memory; executive ID VOXEL-BASED MORPHOMETRY; GRAY-MATTER LOSS; HIPPOCAMPAL VOLUME; STRUCTURAL MRI; TEMPORAL-LOBE; OLDER-ADULTS; ATROPHY; AD; RECOLLECTION; FAMILIARITY AB In Alzheimer's disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. RP Duarte, A (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 2EF, England. EM audrey.duarte@mrc-cbu.cam.ac.uk FU NIA NIH HHS [2R01AG10897-18, P01 AG012435, R01 AG010897] NR 27 TC 41 Z9 45 U1 0 U2 5 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 OCT 2 PY 2006 VL 406 IS 1-2 BP 60 EP 65 DI 10.1016/j.neulet.2006.07.029 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 087XH UT WOS:000240775600012 PM 16904823 ER PT J AU Welch, S Augustine, J Camargo, CA Reese, C AF Welch, Shari Augustine, James Camargo, Carlos A., Jr. Reese, Charles TI Emergency department performance measures and benchmarking summit SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE quality improvement; benchmarking; ED operations; performance measures; process improvement AB The findings are presented of a consensus group created to address the standardization of performance measures for emergency medicine. This group, whose members have affiliations with most major organizations interested in emergency medicine performance, benchmarking and quality improvement, was tasked with standardizing definitions pertinent to emergency department performance measures, creating a set of general and operational measures, developing a comparison system for benchmarking and creating a plan for the dissemination of this information. The formation of this group, the problem statement, and the mission statement for the summit are all described, and the consensus document is presented. C1 Univ Utah, Sch Med, LDS Hosp, Emergency Dept, Salt Lake City, UT 84143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Christiana Care, Wilmington, DE USA. RP Welch, S (reprint author), Univ Utah, Sch Med, LDS Hosp, Emergency Dept, 8th Ave & C St, Salt Lake City, UT 84143 USA. EM sjwelch@networld.com NR 0 TC 52 Z9 52 U1 0 U2 4 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2006 VL 13 IS 10 BP 1074 EP 1080 AR PII ISSN 1069-6563583 DI 10.1197/j.aem.2006.05.026 PG 7 WC Emergency Medicine SC Emergency Medicine GA 095NC UT WOS:000241313600012 PM 16946283 ER PT J AU Ingelsson, M Ramasamy, K Cantuti-Castelvetri, I Skoglund, L Matsui, T Orne, J Kowa, H Raju, S Vanderburg, CR Augustinack, JC de Silva, R Lees, AJ Lannfelt, L Growdon, JH Frosch, MP Standaert, DG Irizarry, MC Hyman, BT AF Ingelsson, Martin Ramasamy, Karunya Cantuti-Castelvetri, Ippolita Skoglund, Lena Matsui, Toshifumi Orne, Jennifer Kowa, Hasimoto Raju, Susan Vanderburg, Charles R. Augustinack, Jean C. de Silva, Rohan Lees, Andrew J. Lannfelt, Lars Growdon, John H. Frosch, Matthew P. Standaert, David G. Irizarry, Michael C. Hyman, Bradley T. TI No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer's disease brain SO ACTA NEUROPATHOLOGICA LA English DT Article DE brain; neurodegeneration; Alzheimer's disease; tau; alternative splicing ID PROGRESSIVE SUPRANUCLEAR PALSY; PROTEIN-TAU; ABNORMAL PHOSPHORYLATION; NEUROFIBRILLARY TANGLES; CEREBROSPINAL-FLUID; MESSENGER-RNA; ISOFORMS; FTDP-17; STANDARDIZATION; ACCUMULATION AB Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R tau) and without (3R tau) exon 10, is believed to be a pathological consequence of certain tau mutations causing frontotemporal dementia. By assessing protein and mRNA levels of 4R tau and 3R tau in 27 AD and 20 control temporal cortex, we investigated whether altered tau splicing is a feature also in Alzheimer's disease (AD). However, apart from an expected increase of sarcosyl-insoluble tau in AD, there were no significant differences between the groups. Next, by laser-capture microscopy and quantitative PCR, we separately analyzed CA1 hippocampal neurons with and without neurofibrillary pathology from six of the AD and seven of the control brains. No statistically significant differences in 4R tau/3R tau mRNA were found between the different subgroups. Moreover, we confirmed the absence of significant ratio differences in a second data set with laser-captured entorhinal cortex neurons from four AD and four control brains. Finally, the 4R tau/3R tau ratio in CA1 neurons was roughly half of the ratio in temporal cortex, indicating region-specific differences in tau mRNA splicing. In conclusion, this study indicated region-specific and possibly cell-type-specific tau splicing but did not lend any support to overt changes in alternative splicing of tau exon 10 being an underlying factor in AD pathogenesis. C1 Uppsala Univ, Dept Publ Hlth Mol Geriatr, S-75185 Uppsala, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. UCL, Reta Lila Weston Inst Neurol Studies, London WC1N 1PJ, England. RP Ingelsson, M (reprint author), Uppsala Univ, Dept Publ Hlth Mol Geriatr, Dag Hammarskjolds Vag 20, S-75185 Uppsala, Sweden. EM martin.ingelsson@pubcare.uu.se RI de Silva, Rohan/C-1734-2008; Lees, Andrew/A-6605-2009; OI de Silva, Rohan/0000-0002-5052-5775; Standaert, David/0000-0003-2921-8348 FU Medical Research Council [G0501560, G0501560(76517)]; NIA NIH HHS [AG08487, P50 AG005134] NR 28 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD OCT PY 2006 VL 112 IS 4 BP 439 EP 449 DI 10.1007/s00401-006-0095-3 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 089QC UT WOS:000240894600005 PM 16802167 ER PT J AU Burroughs, BR Muratoglu, OK Bragdon, CR Wannomae, KK Christensen, S Lozynsky, AJ Harris, WH AF Burroughs, Brian R. Muratoglu, Orhun K. Bragdon, Charles R. Wannomae, Keith K. Christensen, Steven Lozynsky, Andrew J. Harris, William H. TI In vitro comparison of frictional torque and torsional resistance of aged conventional gamma-in-nitrogen sterilized polyethylene versus aged highly crosslinked polyethylene articulating against head sizes larger than 32 mm SO ACTA ORTHOPAEDICA LA English DT Article ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; LONG-TERM IMPLANTATION; ACETABULAR COMPONENTS; MECHANICAL-PROPERTIES; FATIGUE RESISTANCE; WEAR; RADIATION; REPLACEMENTS; SOCKETS AB Background The advent of highly crosslinked polyethylene has allowed the re-evaluation of the use of femoral heads larger than 32 mm for metal-on-polyethylene total hip arthroplasties. However, the effect of larger heads on the frictional torque of highly crosslinked polyethylene is unknown. Methods We performed an in vitro examination of the effect of larger chrome cobalt femoral heads (40 mm diameter) on the frictional torque and torsional resistance of hip articulations on aged liners of polyethylene that were sterilized by gamma rays while in nitrogen, and aged highly crosslinked polyethylene. The frictional torque at the femoral head articulation was usually higher for the highly crosslinked polyethylene than for the conventional polyethylene. The aged conventional liners oxidized considerably, which led to gross failure of the polyethylene at the anti-rotation portion of the rim. The aged crosslinked polyethylene showed no such failures despite the higher frictional torque. Interpretation Our findings suggest that in terms of torsional resistance to fatigue when studied as a device, rather than as an isolated material, under these conditions, aged highly crosslinked polyethylene is preferable to aged conventional polyethylene. C1 Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Adult Reconstruct Unit, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St, Boston, MA 02114 USA. EM wharris.obbl@partners.org NR 26 TC 21 Z9 21 U1 0 U2 4 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 J9 ACTA ORTHOP JI Acta Orthop. PD OCT PY 2006 VL 77 IS 5 BP 710 EP 718 DI 10.1080/17453670610012881 PG 9 WC Orthopedics SC Orthopedics GA 090LY UT WOS:000240954000005 PM 17068700 ER PT J AU Watnick, S AF Watnick, Suzanne TI Obesity: A problem of Darwinian proportions? SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE obesity; chronic kidney disease; dialysis; kidney transplantation; bioethics ID BODY-MASS INDEX; STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; METABOLIC SYNDROME; FOLLOW-UP; MORTALITY; DIALYSIS; SURVIVAL AB Obesity has been described as an abnormality arising from the evolution of man, who becomes fat during the time of perpetual plenty. From the perspective of "Darwinian Medicine," if famine is avoided, obesity will prevail. Problems regarding obesity arise within many disciplines, including socioeconomic environments, the educational system, science, law, and government. This article will discuss various ethical aspects of several disciplines regarding obesity, with a focus on scientific inquiry. We will discuss this within the categories: (1) chronic kidney disease predialysis, (2) dialysis, and (3) renal transplantation. This article aims to help nephrologists and their patients navigate through the ethical aspects of obesity and chronic kidney disease. (c) 2006 by the National Kidney Foundation, Inc. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97201 USA. RP Watnick, S (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Dr,P3NEPH, Portland, OR 97239 USA. EM watnicks@ohsu.edu NR 37 TC 7 Z9 7 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2006 VL 13 IS 4 BP 428 EP 432 DI 10.1053/j.ackd.2006.07.005 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 096SH UT WOS:000241396600013 PM 17045229 ER PT J AU Fernandez, E Koek, W Ran, QT Gerhardt, GA France, CP Strong, R AF Fernandez, Elizabeth Koek, Wouter Ran, Qitao Gerhardt, Greg A. France, Charles P. Strong, Randy TI Monoamine metabolism and behavioral responses to ethanol in mitochondrial aldehyde dehydrogenase knockout mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE mitochondrial aldehyde dehydrogenase; ALDH2; monoamines; ethanol ID RETINOIC ACID SYNTHESIS; RAT-LIVER; ALCOHOL SENSITIVITY; DOPAMINE METABOLISM; BIOGENIC ALDEHYDES; PREFERENCE; MOUSE; ACETALDEHYDE; OXIDATION; DAIDZIN AB Background: It is widely accepted that, in addition to removing acetaldehyde produced during the metabolism of ethanol, mitochondrial aldehyde dehydrogenase (ALDH2) functions in the pathway by which aldehyde metabolites of the monoamines dopamine (DA) and serotonin (5-HT) are converted to their acidic metabolites. Moreover, studies of ALDH2 inhibitors used for treating alcoholism suggest that their antidipsotropic effects may be related to inhibition of monoamine metabolism. Therefore, we examined the hypothesis that altered brain monoamine metabolism is related to the influence of ALDH2 on behavioral responses to ethanol. Methods: Mice were generated with a gene-trap mutation of the ALDH2 gene. ALDH2 mRNA was absent in ALDH2-/- mice. Western blot analysis of liver mitochondria confirmed the absence of ALDH2 protein in the ALDH2-/- mice. Wild-type and ALDH2-deficient mice were tested for the effects of different doses of ethanol on locomotor activity, ataxia, and a 2-bottle ethanol-water preference test. Results: Wild-type and ALDH2+/- mice preferred ethanol to water. However, ALDH2-/- mice drank significantly less ethanol than wild-type or ALDH2+/- mice. Locomotor activity and ataxia were significantly more affected by ethanol in ALDH2-/- mice than in wild-type or ALDH2+/- mice. There was no effect of genotype on levels of 5-HT, DA, or their precursors or metabolites in several brain regions, as measured by HPLCec. Conclusions: The results indicate that: (1) the effect of the mutant genotype on behavioral responses to ethanol is unrelated to altered brain monoamine metabolism and (2) ALDH2 is not required for the metabolism of brain monoamines in vivo. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat & Cellular & Struct Biol, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Res Serv & Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. Univ Kentucky, Albert B Chandler Med Ctr, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Univ Kentucky, Albert B Chandler Med Ctr, Dept Neurol & Psychiat, Lexington, KY 40536 USA. RP Strong, R (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 1355 Lambda Dr,MSC 7755, San Antonio, TX 78245 USA. EM strong@uthscsa.edu FU NIA NIH HHS [AG022307, AG022014]; NIDA NIH HHS [DA17198, K05 DA017918]; NINDS NIH HHS [NS039787] NR 37 TC 10 Z9 10 U1 1 U2 3 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 OCT PY 2006 VL 30 IS 10 BP 1650 EP 1658 DI 10.1111/j.1530-0277.2006.00200.x PG 9 WC Substance Abuse SC Substance Abuse GA 088NO UT WOS:000240818600009 PM 17010132 ER PT J AU Parnell, SE Dehart, DB Wills, TA Chen, S Hodge, CW Besheer, J Waage-Baudet, HG Charness, ME Sulik, KK AF Parnell, Scott E. Dehart, Deborah B. Wills, Tiffany A. Chen, Shao-yu Hodge, Clyde W. Besheer, Joyce Waage-Baudet, Heather G. Charness, Michael E. Sulik, Kathleen K. TI Maternal oral intake mouse model for fetal alcohol spectrum disorders: Ocular defects as a measure of effect SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE fetal alcohol spectrum disorders; model; eye; alcohol deprivation; in vivo ID PRENATAL ETHANOL EXPOSURE; MICE; MALFORMATIONS; CHILDREN; DIAGNOSIS; RATS AB Background: This work was conducted in an effort to establish an oral intake model system in which the effects of ethanol insult that occur during early stages of embryogenesis can be easily examined and in which agents that may modulate ethanol's teratogenicity can be readily tested in vivo. The model system described utilizes the alcohol deprivation effect to obtain teratogenic levels of maternal ethanol intake on days 7 and 8 of pregnancy in C57Bl/6J mice. Ocular defects including microphthalmia and uveal coloboma, which have previously been shown to result from ethanol administered by gavage or via intraperitoneal injection on these days, served as the developmental end point for this study. The ocular defects are readily identifiable and their degree of severity is expected to correlate with concurrently developing defects of the central nervous system (CNS). Methods: Female C57Bl/6J mice were maintained on an ethanol-containing (4.8% v/v) liquid diet for 14 days and then mated during a subsequent abstinence period. Mice were then reexposed to ethanol on days 7 and 8 of pregnancy only. Control as well as ethanol-exposed dams were killed on their 14th day of pregnancy. Fetuses were then weighed, measured for crown rump length, photographed, and analyzed for ocular abnormalities. Globe size, palpebral fissure length, and pupil size and shape were noted for both the right and left eyes of all fetuses and informative comparisons were made. Results: This exposure paradigm resulted in peak maternal blood alcohol concentrations that ranged from 170 to 220 mg/dL on gestational day (GD) 8. Compared with the GD 14 fetuses from the normal control group, the pair-fed, acquisition controls, as well as the ethanol-exposed fetuses, were developmentally delayed and had reduced weights. Confirming previous studies, comparison of similarly staged control and treated GD 8 embryos illustrated reductions in the size of the forebrain in the latter. Subsequent ocular malformations were noted in 33% of the right eyes and 25% of the left eyes of the 103 GD 14 ethanol-exposed fetuses examined. This incidence of defects is twice that observed in the control groups. Additionally, it was found that the palpebral fissure length is directly correlated with globe size. Conclusions: The high incidence of readily identifiable ocular malformations produced by oral ethanol intake in this model and their relevance to human fetal alcohol spectrum disorders (FASD) makes this an excellent system for utilization in experiments involving factors administered to the embryo that might alter ethanol's teratogenic effects. Additionally, the fact that early ethanol insult yields ocular and forebrain abnormalities that are developmentally associated allows efficient specimen selection for subsequent detailed analyses of CNS effects in this in vivo mammalian FASD model. C1 Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, W Roxbury, MA USA. RP Parnell, SE (reprint author), Univ N Carolina, Bowles Ctr Alcohol Studies, CB 7178, Chapel Hill, NC 27599 USA. EM sparnell@med.unc.edu OI Charness, Michael/0000-0002-3301-8966 FU NIAAA NIH HHS [K01 AA013908, AA013908, AA014983, AA11605, AA12974] NR 28 TC 37 Z9 38 U1 0 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 OCT PY 2006 VL 30 IS 10 BP 1791 EP 1798 DI 10.1111/j.1530-0277.2006.00212.x PG 8 WC Substance Abuse SC Substance Abuse GA 088NO UT WOS:000240818600023 PM 17010146 ER PT J AU Chapko, MK Dominitz, JA AF Chapko, M. K. Dominitz, J. A. TI Cost-effectiveness of growth factors during hepatitis C anti-viral therapy SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ALPHA-2B PLUS RIBAVIRIN; HCV-INFECTED PATIENTS; RED-CELL APLASIA; RIBAVIRIN/INTERFERON-INDUCED ANEMIA; QUALITY-OF-LIFE; EPOETIN-ALPHA; PEGINTERFERON ALPHA-2B; COMBINATION THERAPY; INITIAL TREATMENT; INTERFERON-ALPHA AB Background Although the current standard of care for controlling anaemia and neutropenia during anti-viral therapy for hepatitis C is to use dose reduction of ribavirin and pegylated interferon, respectively, erythropoietin and granulocyte colony-stimulating factor are now being advocated as alternatives to dose reduction. Aim To determine the cost-effectiveness of erythropoietin and granulocyte colony-stimulating factor as an alternative to anti-viral dose reduction during antihepatitis C therapy. Methods Decision analysis was used to assess cost-effectiveness by estimating the cost of using a growth factor per quality-adjusted life-year gained. Results Under baseline assumptions, the cost per quality-adjusted life-year of using growth factors ranged from $16 247 for genotype 1 with neutropenia to $145 468 for genotype 2/3 patients with anaemia. These findings are sensitive to the relationship between dose reduction and sustained virological response. Conclusions Based upon our findings and the varying strength of the evidence for a relationship between dose reduction and sustained virological response: granulocyte colony-stimulating factor may be cost-effective for genotype 1 patients; erythropoietin is probably not cost-effective for genotype 2/3 patients; no conclusion can be reached regarding the cost-effectiveness of erythropoietin for genotype 1 patients or granulocyte colony-stimulating factor for genotype 2/3 patients. Randomized trials are needed to firmly establish the relationship between dose reduction and sustained virological response. C1 VA Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Div Gastroenterol, Dept Med, Seattle, WA 98195 USA. RP Chapko, MK (reprint author), VA Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM chapko@u.washington.edu OI Dominitz, Jason/0000-0002-8070-7086 NR 53 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD OCT 1 PY 2006 VL 24 IS 7 BP 1067 EP 1077 DI 10.1111/j.1365-2036.2006.03089.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 083FH UT WOS:000240441300009 PM 16984501 ER PT J AU Hyman, BT AF Hyman, Bradley T. TI Natural history of Alzheimer disease dissected through multiphoton imaging of transgenic mice SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; MOUSE MODEL; NEURONAL LOSS; MICROSCOPY; PLAQUES; MEMORY; TAU C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, 114 16th St, Charlestown, MA 02129 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2006 VL 20 IS 4 BP 206 EP 209 DI 10.1097/01.wad.0000213850.51495.0f PG 4 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 117OX UT WOS:000242883700005 PM 17132963 ER PT J AU Sano, M Egelko, S Jin, S Cummings, J Clark, CM Pawluczyk, S Thomas, RJ Schittini, M Thal, LJ AF Sano, Mary Egelko, Susan Jin, Shelia Cummings, Jeffrey Clark, Christopher M. Pawluczyk, Sonia Thomas, Ronald J. Schittini, Mario Thal, Leon J. CA Alzheimers Dis Cooperative St TI Spanish instrument protocol: New treatment efficacy instruments for Spanish-speaking patients in Alzheimer disease clinical trials SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; Spanish language assessment; outcome measures; clinical trials ID BEHAVIOR RATING-SCALE; MULTICENTER EVALUATION; DEMENTIA; VALIDITY AB Objective: To evaluate the feasibility of longitudinal assessment and the psychometric properties of both established and new outcome measures used in clinical trials of patients with dementia in a cohort of Spanish-speaking elders in the United States. Methods: This is a prospectively collected multicenter study comparing patients with Alzheimer disease (AD) (N = 77) and elderly controls (N = 17) who are primary Spanish speakers. Spanish-speaking individuals with AD (SSI AD) were selected to represent predefined categories of impairment as determined by a Mini-Mental State Examination score. Controls were selected to approximately match by age and education (SSI C). Subjects were administered a series of Spanish translations of established outcome measures (Mini-Mental State Examination., Clinical Dementia Rating, Geriatric Dementia Scale), and Functional Assessment Staging (FAST)] and new outcome measures developed for United States in clinical trials to assess cognition, function, behavioral disturbance, and clinical global change. Half of the subjects were assessed at 1 and 2 months to evaluate reliability; all subjects were assessed at 6 and 12 months. Comparisons were made between patients and controls and between the Spanish-speaking cohort and a similar English-speaking cohort. Results: The 12-month completion rate was 77%, with a trend toward greater impairment in those with full retention. Both established and new measures demonstrated good internal consistency and test-retest reliability in this cohort. All but one measure of cognition demonstrated excellent discriminability between AD subjects and controls. The SSI AD cohort declined significantly on measures of cognition, function, and clinical global change over the 12-month assessment period. The SSI AD and English AD (ESI AD) cohorts declined equivalently on the most common outcomes in clinical trials of AD (delayed recall, clinical global change). Likewise, the most common behavioral changes were also similar in the ESI and SSI groups. However, the annual change was lower in SSI AD than in the ESI AD on several other measures of cognition and function. Conclusions: These results support the recruitment of Spanish-speaking patients and the use of Spanish language translations for use in the clinical trials for AD. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Bronx, NY USA. Psychol Consulting Practice, New York, NY USA. UCSD, Alzheimers Dis Cooperat Study, La Jolla, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Univ Penn, Alzheimers Dis Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. RP Sano, M (reprint author), Bronx Vet Adm Med Ctr, 139 W Kingsbridge Rd,Code 151 Rm 1F01, Bronx, NY 10468 USA. EM Mary.Sano@mssm.edu FU NIA NIH HHS [AG05138, U01 AG10483, P50 AG005138, U19 AG010483, P50 AG005138-20, U01 AG010483, U01 AG010483-18] NR 21 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2006 VL 20 IS 4 BP 232 EP 241 DI 10.1097/01.wad.0000213862.20108.f5 PG 10 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 117OX UT WOS:000242883700009 PM 17132967 ER PT J AU Greenberg, SM Rosand, J Schneider, AT Pettigrew, LC Gandy, SE Rovner, B Fitzsimmons, BF Smith, EE Gurol, ME Schwab, K Laurin, J Garceau, D AF Greenberg, Steven M. Rosand, Jonathan Schneider, Alexander T. Pettigrew, L. Creed Gandy, Samuel E. Rovner, Barry Fitzsimmons, Brian-Fred Smith, Eric E. Gurol, M. Edip Schwab, Kristin Laurin, Julie Garceau, Denis TI A phase 2 study of tramiprosate for cerebral amyloid angiopathy SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE cerebral amyloid angiopathy; clinical drug trial; glycosaminoglycans ID LOBAR INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS; GLYCOSAMINOGLYCANS; SCALE; RISK AB Background and Purpose: No treatments have been identified to lower the risk of intracerebral hemorrhage due to cerebral amyloid angiopathy (CAA). A potential approach to prevention is the use of agents that interfere with the pathogenic cascade initiated by the beta-amyloid peptide (A beta). Tramiprosate (3-amino-1-propanesulfonic acid) is a candidate molecule shown in preclinical studies to reduce CAA in a transgenic mouse model. Methods: We performed a 5-center phase 2 double-blinded trial to evaluate the safety, tolerability, and pharmacokinetics of tramiprosate in subjects with lobar intracerebral hemorrhage. Twenty-four subjects age >= 55 years with possible or probable CAA were randomized to receive 12 weeks of tramiprosate at 1 of 3 oral doses (50, 100, or 150 mg twice daily). Subjects were followed for clinical adverse effects, laboratory, vital sign, electrocardiogram, cognitive, or functional changes, appearance of new symptomatic or asymptomatic hemorrhages, and pharmacokinetic parameters. Results: Enrolled subjects were younger (mean age 70.8 +/- 5.4, range 61 to 78) and had more advanced baseline disease (measured by number of previous hemorrhages) than consecutive subjects in a CAA natural history cohort. No concerning safety issues were encountered with treatment. Nausea and vomiting were the most common adverse events and were more frequent at high doses. Nine subjects had new symptomatic or asymptomatic hemorrhages during treatment; all occurred in subjects with advanced baseline disease, with no apparent effect of drug dosing assignment. Conclusions: These data suggest that tramiprosate can be given safely to subjects with suspected CAA and support future efficacy trials. C1 Massachusetts Gen Hosp, JP Kistler Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Univ Kentucky, Lexington, KY USA. Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA 19107 USA. Columbia Univ, Med Ctr, New York, NY USA. Neurochem Inc, Laval, PQ, Canada. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, JP Kistler Stroke Res Ctr, Dept Neurol, 175 Cambridge St, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Smith, Eric/C-5443-2012; Gurol, Edip/J-2279-2014 OI Smith, Eric/0000-0003-3956-1668; Gurol, Edip/0000-0002-2169-4457 FU NCRR NIH HHS [M01 RR01066]; NIA NIH HHS [P01 AG010491, P01 AG010491-14]; NINDS NIH HHS [R01 NS41409] NR 23 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2006 VL 20 IS 4 BP 269 EP 274 DI 10.1097/01.wad.0000213845.28624.f4 PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 117OX UT WOS:000242883700014 PM 17132972 ER PT J AU Craft, S AF Craft, Suzanne TI Insulin resistance syndrome and Alzheimer disease: pathophysiologic mechanisms and therapeutic implications SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Review DE insulin; Alzheimer disease; diabetes; amyloid ID HYPOGLYCEMIC AGENT CS-045; COGNITIVE IMPAIRMENT; OLDER-ADULTS; MEMORY; BETA; ROSIGLITAZONE; INCREASES; TRANSPORT; GENOTYPE; GLUCOSE AB Insulin plays a key role in cognition and other aspects of normal brain function. Insulin resistance induces chronic peripheral insulin elevations, reduces insulin activity, and reduces brain insulin levels. The insulin resistance syndrome and associated conditions such as type 2 diabetes mellitus and hypertension, are associated with age-related memory impairment and Alzheimer disease. Our work has focused on potential mechanisms through which this association is forged, including the effects of peripheral hyperinsulinemia on memory, inflammation, and regulation of the beta-amyloid peptide. We have shown that raising plasma insulin to levels that characterize patients with insulin resistance invokes synchronous increases in levels of beta-amyloid and inflammatory agents. These convergent effects may impair memory and induce AD pathology. Therapeutic strategies focused on preventing or correcting insulin abnormalities may thus benefit adults with age-related memory impairment and AD. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr,Dept Psychiat & Behav, Seattle, WA 98195 USA. RP Craft, S (reprint author), VAPSHCS, GRECC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu FU NIA NIH HHS [R01 AG-10880] NR 22 TC 98 Z9 103 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2006 VL 20 IS 4 BP 298 EP 301 DI 10.1097/01.wad.0000213866.86934.7e PG 4 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 117OX UT WOS:000242883700019 PM 17132977 ER PT J AU Sano, M Zhu, CW Whitehouse, PJ Edland, S Jin, SL Ernstrom, K Thomas, RG Thal, LJ Ferris, SH AF Sano, Mary Zhu, Carolyn W. Whitehouse, Peter J. Edland, Steven Jin, Shelia Ernstrom, Karin Thomas, Ronald G. Thal, Leon J. Ferris, Steven H. CA Alzheimer Dis Cooperative St TI ADCS Prevention Instrument Project: Pharmacoeconomics: Assessing health-related resource use among healthy elderly SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; primary prevention; assessment measure; resource use; health care utilization; clinical trials ID SEVERE ALZHEIMERS-DISEASE; CAREGIVER TIME; DONEPEZIL TREATMENT; DOUBLE-BLIND; MODERATE; TRIAL; CARE; GALANTAMINE; DEMENTIA; COSTS AB Background: The Prevention Instrument project of the Alzheimer's Disease Cooperative Study (ADCS) seeks to develop instruments to assess treatment efficacy including potential economic benefit. The Resource Use Inventory (RUI) is an instrument that has been used to capture resource utilization and costs in populations with Alzheimer disease (AD). However, resource utilization and costs for healthy, cognitively intact elderly as they begin to demonstrate cognitive deterioration are not well understood. In addition, the loss that relates to the subjects' own time as they transition through cognitive impairment is not well documented. Objectives: To evaluate the utility of the RUI in a sample of cognitively intact elderly individuals living in the community and enrolled in AD prevention trials. Methods: The RUI was administered to 644 subjects and their study partners either at home or in the clinic. For half of each sample, 3-month retesting was carried out. The RUI consisted of 9 questions. The first part of the RUI captured subjects' use of direct medical care (eg, hospitalizations) and nonmedical care (eg, home health aides). The second part of the RUI captured the time caregivers spend providing care to the subjects. The third part of the RUI captured subjects' participation in volunteer work and employment. The assessment interval for each question was the past 3 months. Results: The percentage of RUI forms returned incomplete or inaccurate for both in-clinic and at-home groups was extremely low. There were no differences in utilization rates between in-clinic and at-home group for all items in the RUI. Except for use of outpatient procedures, tests, or treatments, there were no differences in utilization rates between subjects who filled out the RUI with the help of their study partners or by themselves. Items in the RUI were sensitive to subjects' cognitive and functional status and demographic characteristics. Conclusions: Home-based completion of the RUI by participants in an AD prevention study is feasible, and seems to provide data that are reliable and valid. The instrument will be useful for tracking resource and time use through transition from healthy to cognitive impairment. C1 Mt Sinai Sch Med, Bronx, NY 10468 USA. James J Peters VAMC, Bronx, NY 10468 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NYU, Sch Med, Alzheimers Dis Ctr, Silberstein Inst Aging & Dementia, New York, NY USA. RP Sano, M (reprint author), Mt Sinai Sch Med, 130 Kingsbridge Rd,Rm1F01, Bronx, NY 10468 USA. EM mary.sano@mssm.edu FU NIA NIH HHS [U01 AG010483, P50 AG005138, U01 AG 10483, U19 AG010483, P50 AG005138-19] NR 19 TC 17 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2006 VL 20 IS 4 SU 3 BP S191 EP S202 PG 12 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 119JD UT WOS:000243007700009 PM 17135812 ER PT J AU Higgins, JP Williams, G Nagel, JS Higgins, JA AF Higgins, John P. Williams, Gethin Nagel, James S. Higgins, Johanna A. TI Left bundle-branch block artifact on single photon emission computed tomography with technetium Tc 99M (Tc-99m) agents: Mechanisms and a method to decrease false-positive interpretations SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; EXERCISE ECHOCARDIOGRAPHY; STRESS ECHOCARDIOGRAPHY; DOBUTAMINE STRESS; SPECT; PERFUSION; DIAGNOSIS; TL-201; SCINTIGRAPHY AB Myocardial perfusion scintigraphy is a well validated noninvasive method of evaluating for significant coronary artery disease, especially in cases where electrocardiographic changes are nondiagnostic, including left bundle-branch block. However, such testing with a technetium Tc 99m agent is often confounded by left ventricular septal-based false-positive perfusion defects. These defects can be either reversible or irreversible in the septal or anteroseptal wall, problematically then, in the territory supplied by the left anterior descending coronary artery. Mechanisms explaining false-positive defects include decreased perfusion via impaired microvessel flow and normal perfusion with apparent decrease in counts in a relatively thin septum (partial-volume effect). Key findings in myocardial perfusion images in the presence of left bundle-branch block that define true positives (ischemia) are reversible perfusion defects (especially at end diastole), a concomitant apical defect, and systolic dysfunction matching the perfusion defect. C1 Harvard Univ, Sch Med, Cardiac Stress Lab, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiobiol, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Higgins, JP (reprint author), Cardiol Sect, 2C-120,1400 VFW Pkwy, Boston, MA USA. EM john_higgins@va.gov NR 42 TC 22 Z9 24 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 OCT PY 2006 VL 152 IS 4 BP 619 EP 626 DI 10.1016/j.ahj.2006.06.009 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101DO UT WOS:000241719300004 PM 16996825 ER PT J AU Wiviott, SD Antman, EM Gibson, CM Montalescot, G Riesmeyer, J Weerakkody, G Winters, KJ Warmke, JW McCabe, CH Braunwald, E AF Wiviott, Stephen D. Antman, Elliott M. Gibson, C. Michael Montalescot, Gilles Riesmeyer, Jeffrey Weerakkody, Govinda Winters, Kenneth J. Warmke, Jeffrey W. McCabe, Carolyn H. Braunwald, Eugene CA TRITON-TIMI 38 Investigators TI Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38) SO AMERICAN HEART JOURNAL LA English DT Article ID MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; ARTERY-DISEASE; TASK-FORCE; INTERVENTION; CS-747; PRETREATMENT; RESISTANCE; LY640315; ASPIRIN AB Background Dual antiplatelet therapy with aspirin and clopidogrel is standard for prevention of thrombotic complications of percutaneous coronary intervention (PCI). Prasugrel is a thienopyridine that is more potent, more rapid in onset, and more consistent in inhibition of platelets than clopidogrel. TRITON-TIMI 38 is designed to compare prasugrel with clopidogrel in moderate to high-risk patients with acute coronary syndrome (ACS). Study Design TRITON-TIMI 38 is a phase 3, randomized, double-blind, parallel-group, multinational, clinical trial. Approximately 13 000 patients with moderate to high-risk ACS undergoing PCI (9500 unstable angina/non-ST-segment elevation myocardial infarction [MI], 3500 ST-segment elevation MI) will be randomized to prasugrel 60 mg loading dose followed by 10 mg daily or clopidogrel 300 mg loading dose followed by 75 mg daily for up to 15 months. The primary end point is the time of the first event of cardiovascular death, MI, or stroke. Analyses will be performed first in the unstable angina/non-ST-segment elevation MI cohort and, conditionally, on the whole ACS population. Major safety end points include TIMI major and minor bleeding unrelated to coronary artery bypass graft surgery. Conclusions TRITON-TIMI 38 is a phase 3 comparison of prasugrel versus clopidogrel in patients with moderate to high-risk ACS undergoing PCI. In addition, it is the first large-scale clinical events trial to assess whether a thienopyridine regimen that achieves a higher level of inhibition of platelet aggregation than the standard therapy results in an improvement in clinical outcomes. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. Sankyo Pharm Inc, Parsippany, NJ USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 32 TC 184 Z9 193 U1 2 U2 9 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 OCT PY 2006 VL 152 IS 4 BP 627 EP 635 DI 10.1016/j.ahj.2006.04.012 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101DO UT WOS:000241719300005 PM 16996826 ER PT J AU Gibson, CM Kirtane, AJ Murphy, SA Rohrbeck, S Menon, V Lins, J Kazziha, S Rokos, I Shammas, NW Palabrica, TM Fish, P McCabe, CH Braunwald, E AF Gibson, C. Michael Kirtane, Ajay J. Murphy, Sabina A. Rohrbeck, Steve Menon, Venu Lins, Jeffrey Kazziha, Samer Rokos, Ivan Shammas, Nicolas W. Palabrica, Theresa M. Fish, Polly McCabe, Carolyn H. Braunwald, Eugene CA TIMI Study Grp TI Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial SO AMERICAN HEART JOURNAL LA English DT Article ID PRIMARY ANGIOPLASTY; FIBRINOLYTIC THERAPY; RANDOMIZED TRIALS; RECEPTOR BLOCKADE; ABCIXIMAB; FLOW; TIROFIBAN; ARTERY; INHIBITION; OUTCOMES AB Background Early restoration of epicardial flow before primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has been associated with improved clinical outcomes. Methods We hypothesized that early administration of the glycoprotein IIb/IIIa inhibitor eptifibatide in the emergency department (ED) would yield superior epicardial flow and myocardial perfusion before primary PCI compared with initiating eptifibatide after diagnostic angiography in the cardiac catheterization laboratory (CCL). Three hundred forty-three patients with STEMI were randomized to either early ED eptifibatide (n = 180) or CCL eptifibatide (n = 163). Results The primary end point (pre-PCI corrected TIMI frame count) was significantly lower (faster flow) with early eptifibatide (77.5 +/- 32.2 vs 84.3 +/- 30.7, P = .049). The incidence of normal pre-PCI TIMI myocardial perfusion was increased among patients treated in the ED versus CCL (24% vs 14%, P = .026). There was no excess of TIMI major or minor bleeding among patients treated in the ED versus CCL (6.9% [12/174] vs 7.8% [11/142], P = NS). Conclusion A strategy of early initiation of eptifibatide in the ED before primary PCI for STEMI yields superior pre-PCI TIMI frame counts, reflecting epicardial flow, and superior TIMI myocardial perfusion compared with a strategy of initiating eptifibatide in the CCL without an increase in bleeding risk. C1 Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ N Carolina, Charlotte, NC 28223 USA. Tristate Med Grp, Fortwayne, IN USA. Mt Clemens Gen Hosp, Mt Clemens, MI USA. Northridge Hosp, Northridge, CA USA. Midwest Cardiovasc Res Fdn, Davenport, IA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 27 TC 60 Z9 60 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 OCT PY 2006 VL 152 IS 4 BP 668 EP 675 DI 10.1016/j.ahj.2006.06.003 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101DO UT WOS:000241719300010 PM 16996831 ER PT J AU Gibson, CM Kirtane, AJ Morrow, DA Palabrica, TM Murphy, SA Stone, PH Scirica, BM Jennings, LK Herrmann, HC Cohen, DJ McCabe, CH Braunwald, E AF Gibson, C. Michael Kirtane, Ajay J. Morrow, David A. Palabrica, Theresa M. Murphy, Sabina A. Stone, Peter H. Scirica, Benjamin M. Jennings, Lisa K. Herrmann, Howard C. Cohen, David J. McCabe, Carolyn H. Braunwald, Eugene CA TIMI Study Grp TI Association between thrombolysis in myocardial infarction myocardial perfusion grade, biomarkers, and clinical outcomes among patients with moderate- to high-risk acute coronary syndromes: Observations from the randomized trial to evaluate the relative PROTECTion against post-PCI microvascular dysfunction and post-PCI ischemia among antiplatelet and antithrombotic agents-thrombolysis in myocardial infarction 30 (PROTECT-TIMI 30) SO AMERICAN HEART JOURNAL LA English DT Article ID TIMI FRAME COUNT; TISSUE-LEVEL PERFUSION; BLOOD-FLOW; TROPONIN-I; INTERVENTION; ANGIOPLASTY; ELEVATIONS; INSIGHTS; RESERVE; INJURY AB Background A variety of imaging modalities have implicated impaired myocardial perfusion in the pathogenesis of acute coronary syndromes (ACSs). Methods We hypothesized that an abnormal TIMI myocardial perfusion grade (TMPG 0/1/2) and an impaired coronary flow reserve (CFR) as assessed angiographically using the TIMI frame count would be associated with biomarker release, ischemia on Halter monitoring, and adverse clinical outcomes in the PROTECT-TIMI 30 trial of patients with non-ST-elevation ACS undergoing percutaneous coronary intervention (PCI). Results The pre-PCI TMPG was correlated with the baseline as well as peak levels of troponin I (P < .001) and creatine kinase-MB (P < .001) and the post-PCI rise in troponin I (P = .03). The incidence of an ischemic event on Holter by 48 hours was more common among patients with an abnormal post-PCI TMPG (12.5% vs 7.0%, P = .013), and the mean normalized duration of ischemia by 24 hours after PCI on Halter monitoring trended longer among patients with an abnormal post-PCI TMPG (8.9 vs 3.2 minutes, P = .068). In multivariable analyses, an abnormal post-PCI TMPG was the strongest correlate of death, myocardial infarction, or an ischemic event by 48 hours after randomization. In contrast, the post-PCI CFR as assessed angiographically using the TIMI frame count was not associated with the baseline, peak, or absolute rise of any biomarker, Halter findings, or clinical events. Conclusions An abnormal TMPG, but not an angiographic CFR, is associated with biomarker status, the occurrence and duration of Holter ischemia, and adverse clinical outcomes among patients with moderate- to high-risk non-ST-elevation ACS undergoing PCI. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Millennium Pharmaceut, Cambridge, MA USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Gibson, CM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 17 TC 22 Z9 23 U1 0 U2 5 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 OCT PY 2006 VL 152 IS 4 BP 756 EP 761 DI 10.1016/j.ahj.2006.04.016 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101DO UT WOS:000241719300033 PM 16996854 ER PT J AU Gregory, SA Ferencik, M Achenbach, S Yeh, RW Hoffmann, U Inglessis, I Cury, RC Nieman, K McNulty, IA Laffan, JA Pomerantsev, EV Brady, TJ Pomerantsev, EV Brady, TJ Semigran, MJ Jang, IK AF Gregory, Shawn A. Ferencik, Maros Achenbach, Stephan Yeh, Robert W. Hoffmann, Udo Inglessis, Ignacio Cury, Ricardo C. Nieman, Koen McNulty, Iris A. Laffan, Josephine A. Pomerantsev, Eugene V. Brady, Thomas J. Pomerantsev, Eugene V. Brady, Thomas J. Semigran, Marc J. Jang, Ik-Kyung TI Comparison of sixty-four-slice multidetector computed tomographic coronary angiography to coronary angiography with intravascular ultrasound for the detection of transplant vasculopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID IMAGE QUALITY; INTRACORONARY ULTRASOUND; CARDIAC TRANSPLANTATION; QUANTITATIVE PARAMETERS; NONINVASIVE DETECTION; ARTERY STENOSES; ACCURACY; RECIPIENTS; CT; COLLIMATION AB Coronary allograft vasculopathy (CAV) is the most important limitation to long-term survival in adult heart transplant recipients and is difficult to detect without intravascular ultrasound (IVUS). We systematically evaluated the image quality of 64-slice multidetector computed tomographic (MDCT) coronary angiography in heart transplant recipients and tested the hypothesis that this modality is comparable to invasive coronary angiography with IVUS for the detection of CAV. Heart transplant recipients (n = 20) underwent invasive coronary angiography with IVUS and MDCT coronary angiography with a 64-slice scanner. Images were systematically analyzed for image quality and the presence of CAV. In addition, multidetector computed tomography and quantitative coronary angiography were used to measure lumen diameters at prespecified locations., Image quality analysis showed that, despite high mean heart rates (77 +/- 7 beats/min) and body mass index (29.5 +/- 5.3 kg/m(2)), 83% of coronary segments were graded as of excellent or good image quality. On average, 95 +/- 9% of the overall visualized length of the coronary arteries was imaged without motion artifacts' and the mean contrast-to-noise ratio was 11.3 +/- 4.6. Compared with IVUS, multidetector computed tomography had a sensitivity of 70%, specificity of 92%, positive predictive value of 89%, and negative predictive value of 77% for the detection of CAV. MDCT vessel diameter measurements correlated well with those obtained from quantitative coronary angiography (R-2 = 0.89). In conclusion, 64-slice multidetector computed tomography provides good to excellent image quality in heart transplant recipients and has moderate to excellent test characteristics for the detection of CAV. Further, MDCT measurements of lumen diameters correlated well with quantitative coronary angiography. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Med 2, Erlangen, Germany. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. EM jang.ik@mgh.harvard.edu FU NHLBI NIH HHS [5K24HL004021-05, 1T32 HL076136-02, 5K30HL004095-06]; NIBIB NIH HHS [1T32EB001632-01] NR 30 TC 57 Z9 63 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 OCT 1 PY 2006 VL 98 IS 7 BP 877 EP 884 DI 10.1016/j.amjcard.2006.04.027 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 092WU UT WOS:000241128900005 PM 16996866 ER PT J AU Misra, M Tsai, P Anderson, EJ Hubbard, JL Gallagher, K Soyka, LA Miller, KK Herzog, DB Klibanski, A AF Misra, Madhusmita Tsai, Patrika Anderson, Ellen J. Hubbard, Jane L. Gallagher, Katie Soyka, Leslie A. Miller, Karen K. Herzog, David B. Klibanski, Anne TI Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE anorexia nervosa; nutrient intake; vitamin D; energy expenditure; adolescent girls ID RESTING ENERGY-EXPENDITURE; BONE-MINERAL DENSITY; SOLUBLE LEPTIN RECEPTOR; BODY-COMPOSITION; EATING DISORDERS; MACRONUTRIENT INTAKE; GROWTH-HORMONE; YOUNG-WOMEN; FAT MASS; METABOLISM AB Background: Adolescence is a common time for the onset of anorexia nervosa (AN), a condition associated with long-term medical and hormonal consequences. Objective: The objective was to compare the nutrient intakes of community-dwelling girls with AN with those of healthy adolescents and to describe the associations between specific nutrient intakes and nutritionally dependent hormones. Design: Nutrient intakes in 39 community-dwelling girls with AN and 39 healthy adolescents aged 12.1-18.7 y were determined by using 4-d food records. Fasting adiponectin, leptin, ghrelin, insulin, and insulin-like growth factor I (IGF-I) concentrations were measured. Indirect calorimetry was used to assess respiratory quotient and resting energy expenditure. Results: In contrast with the control group, the AN group consumed fewer calories from fats (P < 0.0001) and more from carbohydrates (P = 0.0009) and proteins (P < 0.0001). Intake of individual fat components was lower and of dietary fiber higher in the AN group. No significant between-group differences were observed in dietary intakes of calcium, zinc, and iron; however, total intake was greater in the AN group because of greater supplement use (P = 0.006, 0.02, and 0.01, respectively). The AN group had greater intakes of vitamins A, D, and K and of most of the B vitamins, and significantly more girls with AN met the Dietary Reference Intake for calcium (P = 0.01) and vitamin D (P = 0.02) from supplement use. Fat intake predicted ghrelin, insulin, and IGF-I concentrations; carbohydrate intake predicted adiponectin. Resting energy expenditure was lower (P < 0.0001) and leisure activity levels higher in the AN group. Conclusions: Despite outpatient follow-up, community-dwelling girls with AN continue to have lower fat and higher fiber intakes than do healthy adolescents, which results in lower calorie intakes. Nutritionally related hormones are associated with specific nutrient intakes. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Gen Clin Res Ctr, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [K23 RR018851, M01 RR001066, M01-RR-01066]; NIDDK NIH HHS [P30 DK040561, 1R01 DK 062249, DK07703, P30 DK040561-11, R01 DK062249, T32 DK007703] NR 43 TC 57 Z9 60 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2006 VL 84 IS 4 BP 698 EP 706 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700005 PM 17023694 ER PT J AU Litonjua, AA Rifas-Shiman, SL Ly, NP Tantisira, KG Rich-Edwards, JW Camargo, CA Weiss, ST Gillman, MW Gold, DR AF Litonjua, Augusto A. Rifas-Shiman, Sheryl L. Ly, Ngoc P. Tantisira, Kelan G. Rich-Edwards, Janet W. Camargo, Carlos A., Jr. Weiss, Scott T. Gillman, Matthew W. Gold, Diane R. TI Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE asthma; diet; antioxidants; eczema; childhood; wheezing ID ALLERGIC RHINITIS; CHILDHOOD ASTHMA; BLOOD-PRESSURE; HAY-FEVER; NATIONAL-HEALTH; DIETARY FACTORS; UNITED-STATES; LUNG-FUNCTION; T-CELLS; RISK AB Background: Low intakes of dietary antioxidants may contribute to increases in asthma and allergy. Objective: We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children. Design: Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated. and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year. Results: No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% Cl: 0.48,1.03] and zinc (OR: 0.59; 95% Cl: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% Cl: 0.27, 0.90) and zinc (OR: 0.49; 95% Cl: 0.27. 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively). Conclusion: Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Pediat Pulm Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Litonjua, AA (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM augusto.litonjua@channing.harvard.edu FU NHLBI NIH HHS [HL64925, HL61907, K24 HL068041, K24 HL068041-03, R01 HL061907, R01 HL061907-03, R01 HL064925, R01 HL064925-03]; NIAID NIH HHS [AI35786, R01 AI035786, R56 AI035786]; NICHD NIH HHS [HD34568, R01 HD034568, R01 HD034568-03, R37 HD034568] NR 61 TC 117 Z9 123 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2006 VL 84 IS 4 BP 903 EP 911 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700030 PM 17023719 ER PT J AU Slone, S Janckila, A Martin, A Lear, S Yam, L AF Slone, Stephen Janckila, Anthony Martin, Alvin Lear, Sheron Yam, Lung TI Immunohistochemical demonstration of human tartrate-resistant acid phosphatase as a specific biomarker for inflammatory macrophages SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pathology CY OCT 19-22, 2006 CL Los Angeles, NV SP Amer Soc Clin Pathol C1 Univ Louisville, Dept Pathol & Lab Med, Louisville, KY 40292 USA. Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. Univ Louisville, Sch Med, Dept Med, Louisville, KY 40292 USA. US Dept Vet Affairs, Med Ctr, Special Hematol Lab, Louisville, KY 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 OCT PY 2006 VL 126 IS 4 BP 648 EP 648 PG 1 WC Pathology SC Pathology GA 085XY UT WOS:000240638900085 ER PT J AU Abdalla, AI Garcia-Godoy, F AF Abdalla, Ali I. Garcia-Godoy, Franklin TI Clinical evaluation of self-etch adhesives in Class V non-carious lesions SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID RESIN COMPOSITE RESTORATIONS; SHEAR BOND STRENGTH; HYBRID LAYER; DENTIN; SYSTEMS; ENAMEL; ACID; AGGRESSIVENESS; PERFORMANCE; MORPHOLOGY AB Purpose : To evaluate the clinical performance of two self-etching and one total-etch adhesives in Class V non-carious cervical lesions (NCCL). Methods: Two self-etching primers, Clearfil SE Bond and Hybrid Bond, and one total etch adhesive, Admira Bond, were placed in 195 NCCL. Restorations were evaluated at baseline, I and 2 years using the USPHS criteria. Results: No restoration was lost after I and 2 years for all materials. There was no significant difference between the baseline and 2-year results for Admira Bond and Clearfil SE Bond restorations. in contrast, Hybrid Bond restorations showed significant deterioration in marginal adaptation and cavosurface marginal discoloration after 2 years. Also, there was no significant difference between Admira Bond and Clearfil SE Bond at each recall period. C1 Tanta Univ, Fac Dent, Dept Restorat Dent, Tanta, Egypt. Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Ft Lauderdale, FL 33314 USA. Forsyth Inst, Boston, MA USA. RP Abdalla, AI (reprint author), Tanta Univ, Fac Dent, Dept Restorat Dent, Tanta, Egypt. EM aliebraheem01@yahoo.com NR 38 TC 15 Z9 16 U1 0 U2 1 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD OCT PY 2006 VL 19 IS 5 BP 289 EP 292 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 095EH UT WOS:000241290500008 PM 17073206 ER PT J AU Lin, J Zhang, SMM Wu, KN Willett, WC Fuchs, CS Giovannucci, E AF Lin, Jennifer Zhang, Shumin M. Wu, Kana Willett, Walter C. Fuchs, Charles S. Giovannucci, Edward TI Flavonoid intake and colorectal cancer risk in men and women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE colorectal neoplasms; flavones; flavonoids; flavonols ID PROSPECTIVE COHORT; COLON-CANCER; DIETARY FLAVONOIDS; TEA CONSUMPTION; RECTAL-CANCER; HEART-DISEASE; BIOAVAILABILITY; NETHERLANDS; VEGETABLES; HEALTH AB Dietary flavonoids can inhibit cancer development by protecting tissues against free oxygen radicals and inhibiting cell proliferation, but observational studies of flavonoid intake and colorectal cancer incidence are sparse. The authors prospectively evaluated the association between intake of flavonoids and colorectal cancer incidence in 71,976 women from the Nurses' Health Study and 35,425 men from the Health Professionals Follow-Up Study. Dietary intake was assessed in 1990, 1994, and 1998 by means of a food frequency questionnaire. The authors used Cox proportional hazards models with time-varying variables to estimate relative risks of colorectal cancer. Between 1990 and 2000, the authors documented 878 incident cases of colorectal cancer (498 in women and 380 in men). Total flavonoid intake was not inversely associated with colorectal cancer risk among women and men combined. The combined relative risk for the highest quintile of total flavonoid intake compared with the lowest was 1.19 (95% confidence interval: 0.94, 1.49; p for trend = 0.15). Higher intakes of individual flavonols, including quercetin, myricetin, and kaempferol, were also not related to a lower risk of colorectal cancer. These data provide little support for the hypothesis of an association between flavonoid intake and colorectal cancer risk, at least within the ranges of intakes consumed in the populations studied. C1 Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Lin, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med,Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM jhlin@rics.bwh.harvard.edu FU NCI NIH HHS [CA55075, CA87969]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 44 TC 57 Z9 59 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2006 VL 164 IS 7 BP 644 EP 651 DI 10.1093/aje/kwj296 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 086UH UT WOS:000240698000007 PM 16923774 ER PT J AU Gutierrez, A Lee, H Sands, BE AF Gutierrez, Alexandra Lee, Hang Sands, Bruce E. TI Outcome of surgical versus percutaneous drainage of abdominal and pelvic abscesses in Crohn's disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FEATURES AB OBJECTIVE: Abdominal and pelvic abscesses are a common complication of Crohn's disease. We studied the effect of the initial choice of therapy on time to resolution of abdominal and pelvic abscesses. METHODS: We recorded clinical, laboratory, and radiographic data on all adult patients with Crohn's disease and abdominal or pelvic abscesses treated at our institution from 1991 to 2001 and followed >= 1 yr. Univariate analysis identified variables associated with initial choice of drainage modality. These variables were included in a Cox regression model to identify factors independently associated with time to resolution. RESULTS: Of 66 episodes identified, surgery was the initial modality in 29 and percutaneous drainage in 37. Median time to resolution was not different between surgical drainage (25.0 days, range 0-240) and percutaneous drainage (21.5 days, range 0-182) (p = 0.084). Older age, longer duration of symptoms prior to drainage, no fistula identified radiographically, immune modulator use, no rebound tenderness, and admission to the medical service were factors associated with percutaneous drainage as initial modality. These factors, when incorporated in a Cox regression model, did not significantly affect the time to resolution. Days from onset of symptoms to radiographic diagnosis or drainage were independently associated with time to resolution of the abscess. CONCLUSION: Time to resolution of abdominal or pelvic abscesses in Crohn's disease is similar with percutaneous drainage and surgery. One-third of patients treated with percutaneous drainage required surgery within 1 yr. Earlier intervention for abdominal and pelvic abscesses is associated with shorter time to resolution. C1 Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. NR 8 TC 49 Z9 55 U1 0 U2 2 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 OCT PY 2006 VL 101 IS 10 BP 2283 EP 2289 DI 10.1111/j.1572-0241.2006.00757.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 089XL UT WOS:000240915100020 PM 17032194 ER PT J AU Lee, E Winter, ME Boro, MS AF Lee, Elena Winter, Michael E. Boro, Maureen S. TI Comparing two predictive methods for determining serum vancomycin concentrations at a Veterans Affairs medical center SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE antibiotics; blood levels; dosage; drugs, body distribution; equations; methodology; vancomycin; weight ID CREATININE CLEARANCE; RENAL-FUNCTION; THERAPY; PHARMACOKINETICS; PREVALENCE; OBESITY AB Purpose. Two predictive methods for determining serum vancomycin concentrations (SVCs) at a Veterans Affairs medical center were compared. Methods. The data for inpatients at the San Francisco Veterans Affairs Medical Center who received i.v. vancomycin and had vancomycin concentrations recorded in 2003 were included in this retrospective study. Creatinine clearance was estimated by the Cockcroft and Gault equation. Volume of distribution and creatinine clearance were calculated for each patient, using the Leonard and Boro method and the Rushing and Ambrose method. The Sheiner and Beal method for determining precision and bias was used to evaluate whether the two methods significantly differed in their ability to predict SVCs. Results. Of the 223 patients identified, 122 patients were included, and 212 SVCs were analyzed. The population was mostly male and had a mean age of 64.1 years. There were no significant differences in 95% confidence intervals for relative precision and relative bias between the two methods. In patients whose weight was within 120% of their ideal body weight (IBW), the Leonard and Boro, method was significantly more precise and less biased in predicting SVCs. In patients whose weight exceeded 120% of their IBW, the Rushing and Ambrose method was less biased and tended to be more precise, although the difference in precision was not significant. Conclusion. Both methods yielded similar predictability for SVCs in a veterans population. The Leonard and Boro method better predicted SVCs in patients weighing within 120% of their IBW, while the Rushing and Ambrose method appeared to be more appropriate for calculating vancomycin dosages in patients whose weight exceeded 120% of their IBW. C1 San Francisco Vet Affairs Med Ctr, Pharm Serv 119, San Francisco, CA 94121 USA. Kaiser Fdn Hosp, Richmond Med Ctr, Richmond, CA USA. Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. Univ Pacific, Sch Pharm & Hlth Sci, San Francisco, CA USA. RP Boro, MS (reprint author), San Francisco Vet Affairs Med Ctr, Pharm Serv 119, 4150 Clement St, San Francisco, CA 94121 USA. EM maureenboro@va.gov NR 13 TC 5 Z9 6 U1 2 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD OCT 1 PY 2006 VL 63 IS 19 BP 1872 EP 1875 DI 10.2146/ajhp060138 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 091TR UT WOS:000241051700017 PM 16990634 ER PT J AU Pichler, I Marroni, F Volpato, CB Gusella, JF Klein, C Casari, G De Grandi, A Pramstaller, PP AF Pichler, Irene Marroni, Fabio Volpato, Claudia Beu Gusella, James F. Klein, Christine Casari, Giorgio De Grandi, Alessandro Pramstaller, Peter P. TI Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETIC-HETEROGENEITY; SUSCEPTIBILITY LOCUS; RECONSTRUCTION; EPIDEMIOLOGY; CONFIRMATION; DEFINITION; HLODS; 14Q AB Restless legs syndrome (RLS) is a common neurological condition with three loci (12q, 14q, and 9p) described so far, although none of these genes has yet been identified. We report a genomewide linkage scan of patients with RLS (n = 37) assessed in a population isolate (n = 530) of South Tyrol ( Italy). Using both nonparametric and parametric analyses, we initially obtained suggestive evidence of a novel locus on chromosome 2q, with nominal evidence of linkage on chromosomes 5p and 17p. Follow-up genotyping yielded significant evidence of linkage (nonparametric LOD score 5.5, P <= .0000033; heterogeneity LOD score 5.1; alpha = 1.0) on chromosome 2q. Three families (S01, S05, and S016) were shown to descend from a common founder couple. A disease haplotype shared between family S01 and family S05 defines a candidate region of 8.2 cM; in addition, the single affected individual in family S016 shares three linked alleles at neighboring markers, which suggests a reduced candidate interval of only 1.6 cM. Two-point linkage analysis in this 10-generation pedigree provided significant evidence of a novel RLS locus in this region ( LOD score 4.1). These findings reemphasize the genetic heterogeneity of the disorder and strongly support the identification of a novel locus for RLS on chromosome 2q. C1 European Acad, Inst Med Genet, I-39100 Bolzano, Italy. Gen Reg Hosp, Dept Neurol, Bolzano, Italy. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Med Univ Lubeck, Dept Human Genet, D-23538 Lubeck, Germany. Vita Salute Univ, Milan, Italy. San Raffaele Sci Inst, I-20132 Milan, Italy. RP Pramstaller, PP (reprint author), European Acad, Inst Med Genet, Viale Druso 1, I-39100 Bolzano, Italy. EM peter.pramstaller@eurac.edu RI Pramstaller, Peter/C-2357-2008; OI CASARI, Giorgio/0000-0002-0115-8980; Marroni, Fabio/0000-0002-1556-5907 NR 34 TC 68 Z9 71 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2006 VL 79 IS 4 BP 716 EP 723 DI 10.1086/507875 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 089BV UT WOS:000240855900013 PM 16960808 ER PT J AU Zabetian, CP Hutter, CM Yearout, D Lopez, AN Factor, SA Griffith, A Leis, BC Bird, TD Nutt, JG Higgins, DS Roberts, JW Kay, DM Edwards, KL Samii, A Payami, H AF Zabetian, Cyrus P. Hutter, Carolyn M. Yearout, Dora Lopez, Alexis N. Factor, Stewart A. Griffith, Alida Leis, Berta C. Bird, Thomas D. Nutt, John G. Higgins, Donald S. Roberts, John W. Kay, Denise M. Edwards, Karen L. Samii, Ali Payami, Haydeh TI LRRK2 G2019S in families with Parkinson disease who originated from Europe and the Middle East: Evidence of two distinct founding events beginning two millennia ago SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM; COMMON FOUNDER; ASHKENAZI JEWS; GENETIC DRIFT; MUTATION; POPULATIONS; FREQUENT AB The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic determinant of Parkinson disease (PD) identified to date. It accounts for 1%-7% of PD in patients of European origin and 20%-40% in Ashkenazi Jews and North African Arabs with PD. Previous studies concluded that patients from these populations all shared a common Middle Eastern founder who lived in the 13th century. We tested this hypothesis by genotyping 25 microsatellite and single-nucleotide-polymorphism markers in 22 families with G2019S and observed two distinct haplotypes. Haplotype 1 was present in 19 families of Ashkenazi Jewish and European ancestry, whereas haplotype 2 occurred in three European American families. Using a maximum-likelihood method, we estimated that the families with haplotype 1 shared a common ancestor 2,250 (95% confidence interval 1,650 - 3,120) years ago, whereas those with haplotype 2 appeared to share a more recent founder. Our data suggest two separate founding events for G2019S in these populations, beginning at a time that coincides with the Jewish Diasporas. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin,Dept Neurol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Dept Neurol,Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA. New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY USA. Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Zabetian, CP (reprint author), Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin,Dept Neurol, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306; Kay, Denise/0000-0002-9928-2698 FU NIA NIH HHS [P30 AG008017]; NINDS NIH HHS [K08 NS044138, K08 NS044138-04, R01 NS036960] NR 30 TC 74 Z9 75 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2006 VL 79 IS 4 BP 752 EP 758 DI 10.1086/508025 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 089BV UT WOS:000240855900018 PM 16960813 ER PT J AU Bradley, KA Williams, EC Achtmeyer, CE Volpp, B Collins, BJ Kivlahan, DR AF Bradley, Katharine A. Williams, Emily C. Achtmeyer, Carol E. Volpp, Bryan Collins, Bonny J. Kivlahan, Daniel R. TI Implementation of evidence-based alcohol screening in the veterans health administration SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PRIMARY-CARE PATIENTS; AT-RISK DRINKING; BEHAVIORAL-COUNSELING INTERVENTIONS; RANDOMIZED CONTROLLED TRIAL; BRIEF PHYSICIAN ADVICE; GENERAL-PRACTITIONERS; PREVENTIVE-SERVICES; PUBLIC-HEALTH; USE DISORDERS; DRINKERS AB Background: Despite evidence-based guidelines, brief alcohol screening and counseling have not been routinely integrated into most primary care practices in the United States. Objective: To describe the results of the implementation of evidence-based alcohol screening by the Veterans Health Administration (VA) in 2004, as the first step toward implementation of brief alcohol counseling. Study Design: This observational study of outpatients from all 21 VA networks relied on the following 2 data sources from the VA Office of Quality and Performance: (1) Medical record reviews, designed to compare VA networks quarterly, evaluated whether established VA patients had documented screening for alcohol misuse and documented follow-up assessment for alcohol use disorders among those who screened positive for alcohol misuse (January-March 2005); and (2) Mailed patient satisfaction surveys from 2004, which oversampled patients new to the VA (response rate, > 70%), included the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questions and asked about past-year advice "to drink less or not to drink alcohol" from a VA provider. Results: Based on 10 115 medical record reviews, 93% (range, 89%-96% across networks) of outpatients were screened for alcohol misuse, and 25% (range, 11%-36%) screened positive. Among screen-positive patients, 42% (range, 5%-84%) had documented follow-up assessment, but absolute numbers of screen-positive patients evaluated were small (27-80 patients per network). Based on 235 481 patient surveys, the prevalence of alcohol misuse was 22% (range, 15%-27% across networks), and 28% (range, 20%-36%) of screen-positive patients reported receiving alcohol-related advice. Alcohol-related advice increased as AUDIT-C scores increased. Conclusion: The VA successfully implemented evidence-based alcohol screening, but the rate of follow-up among screen-positive patients remained low. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care, Seattle, WA USA. Univ Washington, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA No Calif Healthcare Syst, Martinez, CA USA. VA Off Qual & Performance, Washington, DC USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, 1100 Olive Way,Ste 1400, Seattle, WA 98101 USA. EM willi@u.washington.edu FU NIAAA NIH HHS [K23AA00313] NR 57 TC 107 Z9 107 U1 4 U2 5 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 OCT PY 2006 VL 12 IS 10 BP 597 EP 606 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 099TE UT WOS:000241618000004 PM 17026414 ER PT J AU Federman, AD Halm, EA Zhu, C Hochman, T Siu, AL AF Federman, Alex D. Halm, Ethan A. Zhu, Carolyn Hochman, Tsivia Siu, Albert L. TI Association of income and prescription drug coverage with generic medication use among older adults with hypertension SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID POTENTIAL SAVINGS; CHRONIC ILLNESSES; BENEFIT PLANS; COSTS; PHYSICIAN; CARE; UNDERUSE; SUBSTITUTION; OUTCOMES; COMMUNICATION AB Objective: To determine whether low-income seniors and those without prescription drug coverage are more likely to use generic cardiovascular drugs than more affluent and better insured adults. Study Design: Cross-sectional analysis. Methods: We used data from the 2001 Medicare Current Beneficiary Survey. Analyses included noninstitutionalized survey respondents over age 65 years with hypertension who used >= 1 multisource cardiovascular drugs (N = 1710). We examined the association of income and prescription coverage with use of generic versions of multisource drugs from 5 classes: angiotensin-converting enzyme (ACE) inhibitors, beta-adrenergic receptor antagonists (beta-blockers), calcium channel blockers, alpha-adrenergic receptor antagonists (alpha-blockers), and thiazide diuretics. Results: Rates of generic medication use were 88.5% (beta-blockers); 92.8% (thiazides); 58.7% (calcium channel blockers); 60.7% (ACE inhibitors); and 52.6% (alpha-blockers). In multivariate anaysis of generic medication use aggregated across the 5 drug classes, individuals with incomes below 200% of the federal poverty level were modestly more likely to use generic medications compared with seniors with incomes above 300% the poverty level. Seniors who lacked prescription coverage were more likely to use generics than those who had employer-sponsored coverage, although the association was of marginal statistical significance (relative risk = 1.29, 95% confidence interval = 1.00, 1.60). Conclusion: Seniors with low incomes or no prescription coverage were only somewhat more likely to use generic cardiovascular drugs than more affluent and insured seniors. These findings suggest that physicians and policy makers may be missing opportunities to reduce costs for Medicare and its economically disadvantaged beneficiaries. C1 Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY USA. Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, 1470 Madison Ave,Box 1087, New York, NY 10029 USA. EM alex.federman@mssm.edu FU NIA NIH HHS [K24 AG000918] NR 42 TC 19 Z9 19 U1 1 U2 1 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 OCT PY 2006 VL 12 IS 10 BP 611 EP 618 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 099TE UT WOS:000241618000005 PM 17026415 ER PT J AU Lichtman, JH Fathi, A Radford, MJ Lin, ZQ Loeser, CS Krumholz, HM AF Lichtman, Judith H. Fathi, Amir Radford, Martha J. Lin, Zhenqiu Loeser, Caroline S. Krumholz, Harlan M. TI Acute, severe noncardiac conditions in patients with acute myocardial infarction SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE acute myocardial infarction; mortality; risk factors ID TIMI RISK SCORE; COOPERATIVE CARDIOVASCULAR PROJECT; HEART-FAILURE; MORTALITY; HOSPITALIZATION; COMORBIDITY; DISEASE; TRIAL; THROMBOLYSIS; PREDICTORS AB PURPOSE: The study's purpose was to determine the prevalence and prognostic importance of acute, severe, noncardiac conditions present at the time of an acute myocardial infarction (AMI). METHODS: We identified consecutive patients with AMI who were discharged from Yale-New Haven Hospital between January 1, 1997, and June 30, 2000. Acute, noncardiac conditions that were present at admission were abstracted from patient records and graded by severity (imminent threat to life; other significant condition that would warrant admission). We examined the prognostic importance of these conditions on hospital mortality in multivariable logistic models. The study included 1145 patients with AMI, of whom 8.5% (n = 97) presented with an acute, life-threatening, noncardiac condition at admission and 19.5% (n = 223) presented with another significant noncardiac condition. RESULTS: Hospital mortality was 25.8% and 9.0%, respectively, for patients who presented with life- threatening and other significant noncardiac conditions, compared with 4.6% for patients without either of these conditions. In multivariable analysis, life- threatening noncardiac conditions were associated with increased hospital mortality after adjusting for demographic factors, medical history, clinical presentation, cardiac severity, and initial therapy ( odds ratio 2.5; 95% confidence interval [CI], 1.2- 5.2). No increased hospital mortality risk was found for other significant noncardiac conditions in the risk-adjusted analyses (odds ratio 1.0; 95% CI, 0.5-1.7). CONCLUSIONS: A subgroup of patients with AMI presented with a life- threatening noncardiac condition, which was associated with a marked increase in the risk of death during the hospitalization. Despite the excessive mortality risk associated with concomitant noncardiac conditions, this subset of patients with AMI are poorly described in current literature. (c) 2006 Elsevier Inc. All rights reserved. C1 Yale Univ, Sch Med, Sect Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Sch Med, Sect Chron Dis Epidemiol, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NYU, Med Ctr, Div Cardiol, Dept Med, New York, NY 10016 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Sect Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, 333 Cedar St,POB 208088, New Haven, CT 06520 USA. EM harlan.krumholz@yale.edu OI Radford, Martha/0000-0001-7503-9557 FU NCCDPHP CDC HHS [1 K01 DP000085-01] NR 20 TC 13 Z9 14 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 OCT PY 2006 VL 119 IS 10 BP 843 EP 850 DI 10.1016/j.amjmed.2006.03.040 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 086UX UT WOS:000240699600010 PM 17000215 ER PT J AU Mortensen, EM Restrepo, MI Anzueto, A Pugh, JA AF Mortensen, Eric M. Restrepo, Marcos I. Anzueto, Antonio Pugh, Jacqueline A. TI Antibiotic therapy and 48-hour mortality for patients with pneumonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE antibacterial agents; community-acquired infections; pneumonia ID COMMUNITY-ACQUIRED PNEUMONIA; BACTEREMIC PNEUMOCOCCAL PNEUMONIA; INITIAL ANTIMICROBIAL THERAPY; PROPENSITY SCORE; ELDERLY-PATIENTS; GUIDELINES; MANAGEMENT; OUTCOMES; ADULTS; INPATIENTS AB PURPOSE: Although numerous articles have demonstrated that recommended empiric antimicrobial regimens are associated with decreased mortality at 30 days, there is controversy over whether appropriate antibiotic selection has a beneficial impact on mortality within the first 48 to 96 hours after admission. Our aim was to determine whether the use of guideline-concordant antibiotic therapy is associated with decreased mortality within the first 48 hours after admission for patients with pneumonia. METHODS: A retrospective cohort study was conducted at two tertiary teaching hospitals in San Antonio, Texas. A propensity score was used to balance the covariates associated with the use of guideline-concordant antimicrobial therapy. A multivariable logistic regression model was used to assess the association between mortality within 48 hours and the use of guideline-concordant antibiotic therapy, after adjusting for potential confounders including the propensity score. RESULTS: Information was obtained on 787 patients with community-acquired pneumonia. The median age was 60 years, 79% were male, and 20% were initially admitted to the intensive care unit. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. Within the first 48 hours, 20 patients died. After adjustment for potential confounders, the use of guideline-concordant antimicrobial therapy (odds ratio 0.37, 95% confidence interval, 0.14-0.95) was significantly associated with decreased mortality at 48 hours after admission. CONCLUSION: Using initial empiric guideline-concordant antimicrobial therapy is associated with decreased mortality at 48 hours. Further research needs to investigate methods to ensure that patients with community-acquired pneumonia are treated with appropriate antimicrobial therapies. (c) 2006 Elsevier Inc. All rights reserved. C1 S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Div Gen Internal Med, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Div Pulm Crit Care Med, San Antonio, TX USA. RP Mortensen, EM (reprint author), UTHSCSA, VERDICT, ALMD, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM mortensene@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Mortensen, Eric/0000-0002-3880-5563 NR 27 TC 31 Z9 33 U1 0 U2 1 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 OCT PY 2006 VL 119 IS 10 BP 859 EP 864 DI 10.1016/j.amjmed.2006.04.017 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 086UX UT WOS:000240699600012 PM 17000217 ER PT J AU Frei, CR Restrepo, MI Mortensen, EM Burgess, DS AF Frei, Christopher R. Restrepo, Marcos I. Mortensen, Eric M. Burgess, David S. TI Impact of guideline-concordant empiric antibiotic therapy in community-acquired pneumonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE community-acquired pneumonia; antibiotics; in-hospital mortality; hospital length of stay; time-to-clinical stability; time-to-switch therapy ID INITIAL ANTIMICROBIAL THERAPY; HOSPITALIZED-PATIENTS; ATYPICAL COVERAGE; MANAGEMENT; ADULTS; DIAGNOSIS; SEVERITY; OUTCOMES; INPATIENTS; MORTALITY AB PURPOSE: We evaluated the impact of guideline-concordant empiric antibiotic therapy on time to clinical stability, time to switch therapy, length of hospital stay, and mortality among patients with community-acquired pneumonia. METHODS: This is a retrospective cohort study of all adult community-acquired pneumonia patients managed at 5 community hospitals from November 1, 1999 to April 30, 2000. Patients were stratified into guideline-concordant and discordant groups as defined by the 2001 American Thoracic Society and the 2003 Infectious Diseases Society of America guidelines. Time to clinical stability, time to switch therapy, length of hospital stay, and in-hospital mortality were evaluated in per-protocol and intention-to-treat stepwise regression models that included the outcome as the dependent variable, guideline-concordant antibiotic therapy as the independent variable, and Pneumonia Severity Index score as a covariate. RESULTS: Of the 631 evaluable patients, 357 (57%) received guideline-concordant empiric antibiotic therapy. Groups were similar with respect to age, sex, comorbidities, severity of illness, and processes of care. Guideline-concordant antibiotic therapy was associated with a significant decrease in time to switch therapy (P <=. 01), length of hospital stay (P <=. 01), and in-hospital mortality (P =. 04) for both per-protocol and intention-to-treat analyses. In addition, guideline-concordant antibiotic therapy was associated with a significant decrease in time to clinical stability for intention-to-treat analysis only (P =. 03). CONCLUSIONS: Among hospitalized community-acquired patients, guideline- concordant antibiotic therapy is associated with improved in-hospital survival and shorter time to clinical stability, time to switch therapy, and length of hospital stay. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Clin Pharm Programs, San Antonio, TX 78229 USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Burgess, DS (reprint author), Univ Texas, Hlth Sci Ctr, Clin Pharm Programs, MSC 6220,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM burgessd@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563 NR 30 TC 80 Z9 81 U1 0 U2 3 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 OCT PY 2006 VL 119 IS 10 BP 865 EP 871 DI 10.1016/j.amjmed.2006.02.014 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 086UX UT WOS:000240699600013 PM 17000218 ER PT J AU Anzueto, A AF Anzueto, Antonio TI Clinical course of chronic obstructive pulmonary disease: Review of therapeutic interventions SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; salmeterol; tiotropium ID FLUTICASONE PROPIONATE; MAINTENANCE THERAPY; COPD PATIENTS; TIOTROPIUM; SALMETEROL; EFFICACY; HEALTH; REHABILITATION; COMBINATION; FORMOTEROL AB Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease in which patients experience a progressive decline in lung function. Based on clinical evidence, the management of COPD should focus on (1) earlier diagnosis; (2) risk reduction through smoking cessation, decreased exposure to inhaled irritants, and immunization against respiratory pathogens; (3) symptom reduction with pharmacotherapy and pulmonary rehabilitation; (4) decreasing complications by reducing exacerbations and improving pulmonary function; and (5) improving health-related quality of life (HRQOL). Smoking cessation has been shown to slow lung function decline and to reduce mortality-including deaths due to lung cancer, other respiratory disease (including COPD), and cardiovascular disease. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) and the American Thoracic Society and European Respiratory Society (ATS/ERS) guidelines advocate interventions according to the severity of COPD and recommend initiation of maintenance long-acting bronchodilator therapy in patients with moderate disease. However, recent evidence from a post hoc analysis of randomized controlled trials of tiotropium suggests that initiation of long-acting bronchodilator therapy at earlier stages of disease may also provide improvements in lung function and HRQOL. The results of ongoing long-term studies may soon provide evidence that in addition to relieving symptoms and improving patient HRQOL, specific pharmacologic therapies may also alter the clinical course of COPD. (c) 2006 Elsevier Inc. All rights reserved. C1 Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. RP Anzueto, A (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu NR 25 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD OCT PY 2006 VL 119 IS 10 SU 1 BP S46 EP S53 DI 10.1016/j.amjmed.2006.08.007 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 086SH UT WOS:000240692800007 PM 16996899 ER PT J AU Kajiya, K Hirakawa, S Detmar, M AF Kajiya, Kentaro Hirakawa, Satoshi Detmar, Michael TI Vascular endothelial growth factor-A mediates ultraviolet B-induced impairment of lymphatic vessel function SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TRANSGENIC MICE; HUMAN-SKIN; VEGF-C; TOPICAL TRETINOIN; LYMPHANGIOGENESIS; ANGIOGENESIS; HYPERPLASIA; THROMBOSPONDIN-1; LYMPHEDEMA; OVEREXPRESSION AB UVB irradiation of the skin induces erythema, epidermal hyperplasia, vascular hyperpermeability, and edema formation. Previous studies have revealed that the cutaneous blood vasculature plays a critical role in the mediation of photodamage. In contrast, the role of lymphatic vessels, which play an essential role in the maintenance of tissue fluid balance, in the response to UVB irradiation has remained unknown. We report here that both acute and chronic UVB irradiation of murine skin results in prominent enlargement of lymphatic vessels. Surprisingly, these enlarged lymphatic vessels were functionally impaired and hyperpermeable, as detected by intravital lymphangiography. The expression levels of vascular endothelial growth factor (VEGF)-A but not of the known lymphangiogenesis factors VEGF-C or VEGF-D, were enhanced in UVB-irradiated epidermis. Targeted overexpression of VEGF-A in the epidermis of transgenic mice led to increased enlargement and leakage of lymphatic vessels after acute UVB irradiation, whereas systemic blockade of VEGF-A signaling largely prevented lymphatic vessel abnormalities and photodamage induced by UVB. Together, these findings identify lymphatic vessels as novel targets for UVB-induced cutaneous photodamage and suggest that VEGF-A mediates impairment of lymphatic vessel function, thereby contributing to the adverse effects of UVB irradiation on the skin. C1 ETH, Inst Pharmaceut Sci, Swiss Fed Inst Technol, CH-8093 Zurich, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Detmar, M (reprint author), ETH, Inst Pharmaceut Sci, Swiss Fed Inst Technol, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland. EM michael.detmar@pharma.ethz.ch FU NCI NIH HHS [CA92644, R01 CA086410, CA86410, P01 CA092644, R01 CA069184, CA69184] NR 39 TC 59 Z9 62 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 OCT PY 2006 VL 169 IS 4 BP 1496 EP 1503 DI 10.2353/ajpath.2006.060197 PG 8 WC Pathology SC Pathology GA 089HW UT WOS:000240872400034 PM 17003502 ER PT J AU Berfield, AK Hansen, KM Abrass, CK AF Berfield, Anne K. Hansen, Kim M. Abrass, Christine K. TI Rat glomerular mesangial cells require laminin-9 to migrate in response to insulin-like growth factor binding protein-5 SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE migration; integrins; extracellular matrix ID ALPHA-4 CHAIN; BASEMENT-MEMBRANE; IN-VITRO; G-DOMAIN; ENDOTHELIAL-CELLS; INTEGRIN; DYSTROGLYCAN; EXPRESSION; RECEPTOR; ADHESION AB Temporal and spatial differences in extracellular matrix play critical roles in cell proliferation, differentiation and migration. Different migratory stimuli use different substrates and receptors to achieve cell migration. To understand the mechanism of insulin-like growth factor binding protein-5 (IGFBP5)-induced migration in mesangial cells, the roles of integrins and substrates were examined. IGFBP-5 induced an increase in mRNA expression for laminin (LN) chains lama4, lamb2, and lamc1, suggesting that LN-9 might be required for migration. Antibodies to the LN alpha(4) and LN beta(2) chains, but not LN beta(1), blocked IGFBP-5-induced migration. Anti-sense morpholino oligonucleotide inhibition of expression of LN alpha(4) substantially reduced expression of LN-8/9 (alpha(4)beta(1)gamma(1)/alpha(4)beta(2)gamma(1), 411/421) and prevented IGFBP-5-induced migration. Anti-sense inhibition of lamb2 reduced expression of LN-9. Absence of LN-9 prevented IGFBP-5-induced migration, which was not preserved by continued expression of LN-8. The requirement for LN-9 was further supported by studies of T98G cells, which express predominantly LN-8. IGFBP-5 had little effect on migration in these cells, but increased migration when T98G cells were plated on LN-8/9. IGFBP-5-mediated mesangial cell migration was inhibited by antibodies that block attachment to alpha(6)beta(1)-integrins but was unaffected by antibodies and disintegrins that block binding to other integrins. Furthermore, in cells with anti-sense inhibited expression of LN-9, integrin alpha(6)beta(1) was no longer detected on the cell surface. These studies suggest the specificity of mechanisms of migration induced by specific stimuli and for the first time demonstrate a unique function for LN-9 in mediating IGFBP-5-induced migration. C1 Univ Washington, Dept Med, Sch Med, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Abrass, CK (reprint author), Univ Washington, Dept Med, Sch Med, S Lake Union,815 Mercer St, Seattle, WA 98109 USA. EM cabrass@u.washington.edu FU NIDDK NIH HHS [R01-DK49971-08] NR 66 TC 6 Z9 7 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 2006 VL 291 IS 4 BP C589 EP C599 DI 10.1152/ajpcell.00623.2005 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 084CM UT WOS:000240509400003 PM 16672690 ER PT J AU Krudys, KM Kahn, SE Vicini, P AF Krudys, Kevin M. Kahn, Steven E. Vicini, Paolo TI Population approaches to estimate minimal model indexes of insulin sensitivity and glucose effectiveness using full and reduced sampling schedules SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE two-stage; parameter estimation; minimal model; insulin sensitivity ID RESISTANCE; TOLERANCE; KINETICS; NIDDM AB The intravenous glucose tolerance test (IVGTT) interpreted with the minimal model provides individual indexes of insulin sensitivity (S-I) and glucose effectiveness (S-G). In population studies, the traditional approach, the standard two-stage (STS) method, fails to account for uncertainty in individual estimates, resulting in an overestimation of between-subject variability. Furthermore, in the presence of reduced sampling and/or insulin resistance, individual estimates may be unobtainable, biasing population information. Therefore, we investigated the use of two population approaches, the iterative two-stage (ITS) method and nonlinear mixed-effects modeling (NM), in a population (n = 235) of insulin-sensitive and insulin-resistant subjects under full (FSS, 33 samples) and reduced [RSS(240-min), 13 samples and RSS(180-min), 12 samples] IVGTT sampling schedules. All three population methods gave similar results with the FSS. Using RSS( 240), the three methods gave similar results for S-I, but S-G population means were overestimated. With RSS( 180), S-I and S-G population means were higher for all three methods compared with their FSS counterparts. NM estimated similar between-subject variability (19% S-G, 53% S-I) with RSS(180), whereas ITS showed regression to the mean for S-G (0.01% S-G, 56% S-I) and STS provided larger population variability in S-I (29% S-G, 91% S-I). NM provided individual estimates for all subjects, whereas the two-stage methods failed in 16-18% of the subjects using RSS(180) and 6-14% using RSS(240). We conclude that population approaches, specifically NM, are useful in studies with a sparsely sampled IVGTT (similar to 12 samples) of short duration (similar to 3h) and when individual parameter estimates in all subjects are desired. C1 Univ Washington, Dept Bioengn, Resource Facil Populat Kinet, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Vicini, P (reprint author), Univ Washington, Dept Bioengn, Resource Facil Populat Kinet, Box 352255, Seattle, WA 98195 USA. EM vicini@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NIBIB NIH HHS [P41 EB-001975]; NIDCR NIH HHS [T32 DE-07023]; NIDDK NIH HHS [DK-17047, DK-35816] NR 18 TC 12 Z9 13 U1 0 U2 0 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 OCT PY 2006 VL 291 IS 4 BP E716 EP E723 DI 10.1152/ajpendo.00346.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 086DQ UT WOS:000240654100005 PM 16954338 ER PT J AU Wang, LX Basa, NR Shaikh, A Luckey, A Heber, D St-Pierre, DH Tache, Y AF Wang, Lixin Basa, Nicole R. Shaikh, Almaas Luckey, Andrew Heber, David St-Pierre, David H. Tache, Yvette TI LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE insulin; food intake; gastric emptying; urocortin 1; prostaglandins; interleukin-1; lipopolysaccharide ID CORTICOTROPIN-RELEASING-FACTOR; INSULIN-INDUCED HYPOGLYCEMIA; GROWTH-HORMONE-SECRETION; PITUITARY-ADRENAL AXIS; STIMULATES FOOD-INTAKE; HELICOBACTER-PYLORI; BACTERIAL LIPOPOLYSACCHARIDE; STOMACH GHRELIN; GASTRIC-MUCOSA; IN-VIVO AB LPS injected intraperitoneally decreases fasted plasma levels of ghrelin at 3 h postinjection in rats. We characterized the inhibitory action of LPS on plasma ghrelin and whether exogenous ghrelin restores LPS-induced suppression of food intake and gastric emptying in fasted rats. Plasma ghrelin and insulin and blood glucose were measured after intraperitoneal injection of LPS, intravenous injection of IL-1 beta and urocortin 1, and in response to LPS under conditions of blockade of IL-1 or CRF receptors by subcutaneous injection of IL-1 receptor antagonist (IL-1Ra) or astressin B, respectively, and prostaglandin (PG) synthesis by intraperitoneal indomethacin. Food intake and gastric emptying were measured after intravenous injection of ghrelin at 5 h postintraperitoneal LPS injection. LPS inhibited the elevated fasted plasma ghrelin levels by 47.6 +/- 4.9%, 58.9 +/- 3.3%, 74.4 +/- 2.7%, and 48.9 +/- 8.7% at 2, 3, 5, and 7 h postinjection, respectively, and values returned to preinjection levels at 24 h. Insulin levels were negatively correlated to those of ghrelin, whereas there was no significant correlation between glucose and ghrelin. IL-1Ra and indomethacin prevented the first 3-h decline in ghrelin levels induced by LPS, whereas astressin B did not. IL-1 beta inhibited plasma ghrelin levels, whereas urocortin 1 had no influence. Ghrelin injected intravenously prevented an LPS-induced 87% reduction of gastric emptying and 61% reduction of food intake. These data showed that IL-1 and PG pathways are part of the early mechanisms by which LPS suppresses fasted plasma ghrelin and that exogenous ghrelin can normalize LPS-induced-altered digestive functions. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Ulcer Res & Educ, Digest Dis Res Ctr,Dept Med,Div Digest Dis, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada. RP Wang, LX (reprint author), CURE Bldg 115,Rm 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, P50-DK-64539, R01-DK-33061, R37-DK-33061-17S1] NR 63 TC 57 Z9 58 U1 0 U2 3 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 OCT PY 2006 VL 291 IS 4 BP G611 EP G620 DI 10.1152/ajpgi.00533.2005 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 082CN UT WOS:000240364400009 PM 16959954 ER PT J AU Alfonso-Jaume, MA Bergman, MR Mahimkar, R Cheng, S Jin, ZQ Karliner, JS Lovett, DH AF Alfonso-Jaume, Maria Alejandra Bergman, Marina R. Mahimkar, Rajeev Cheng, Sunfa Jin, Zhu Q. Karliner, Joel S. Lovett, David H. TI Cardiac ischemia-reperfusion injury induces matrix metalloproteinase-2 expression through the AP-1 components FosB and JunB SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE reperfusion injury; transcription factor; activator protein-1 ID GLOMERULAR MESANGIAL CELLS; NF-KAPPA-B; GELATINASE-A; GENE-EXPRESSION; TRANSCRIPTION FACTORS; NITRIC-OXIDE; MYOCARDIAL-ISCHEMIA; C-FOS; ACTIVATION; HEART AB Matrix metalloproteinase-2 (MMP-2) is a central component of the response to injury in the heart. During ischemia, MMP-2 influences ventricular performance and is a determinant of postinfarction remodeling. Elevation of MMP-2 during reperfusion after ischemia suggests that new protein is synthesized, but the molecular regulation of MMP-2 generation during ischemia-reperfusion (I/R) injury has not been studied. Using the MMP-2 promoter linked to a beta-galactosidase reporter in transgenic mice, we investigated the transcriptional regulation and cellular sources of MMP-2 in isolated, perfused mouse hearts subjected to acute global I/R injury. I/R injury induced a rapid activation of MMP-2 promoter activity with the appearance of beta-galactosidase antigen in cardiomyocytes, fibroblasts, and endothelial cells. Activation of intrinsic MMP-2 transcription and translation was confirmed by real-time PCR and quantitative Western blot analyses. MMP-2 transcription and translation were inhibited by perfusion with 1.0 mM hydroxyl radical scavenger N-(-2-mercaptopropionyl)-glycine. Nuclear extracts demonstrated increased abundance of two activator proteins-1 (AP-1) components JunB and FosB following I/ R injury. Immunohistochemical staining localized JunB and FosB proteins to the nuclei of all three cardiac cell types following I/ R injury, consistent with enhanced nuclear transport of these transcription factors. Chromatin immunoprecipitation (ChIP) of the AP-1 binding site in the intrinsic murine MMP-2 promoter yielded only JunB under control conditions, whereas ChIP following I/ R injury recovered both JunB and FosB, consistent with a change in occupancy from JunB homodimers in controls to JunB/FosB heterodimers following I/ R injury. We conclude that enhanced MMP-2 transcription and translation following I/R injury are mediated by induction, via oxidant stress, of discrete AP-1 transcription factor components. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94121 USA. Univ Wisconsin, Sch Med, Dept Med, William S Middleton Vet Affairs Med Ctr, Madison, WI USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. RP Lovett, DH (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM david.lovett@med.va.gov FU NHLBI NIH HHS [P01-HL-68738] NR 44 TC 49 Z9 50 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2006 VL 291 IS 4 BP H1838 EP H1846 DI 10.1152/ajpheart.00026.2006 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 084CP UT WOS:000240509700042 PM 16699069 ER PT J AU Zhu, XS Zhao, HL Graveline, AR Buys, ES Schmidt, U Bloch, KD Rosenzweig, A Chao, W AF Zhu, Xinsheng Zhao, Huailong Graveline, Amanda R. Buys, Emmanuel S. Schmidt, Ulrich Bloch, Kenneth D. Rosenzweig, Anthony Chao, Wei TI MyD88 and NOS2 are essential for Toll-like receptor 4-mediated survival effect in cardiomyocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE signal transduction; cardiac; apoptosis; inducible nitric oxide synthase ID NITRIC-OXIDE SYNTHASE; ISCHEMIA-REPERFUSION INJURY; CARDIAC MYOCYTE APOPTOSIS; FAILING HUMAN HEART; MYOCARDIAL-INFARCTION; DILATED CARDIOMYOPATHY; SERUM DEPRIVATION; S-NITROSYLATION; PROTEIN-KINASE; GROWTH-FACTOR AB Innate immune system such as Toll-like receptor 4 (TLR4) represents the first line of defense against infection. In addition to its pivotal role in host immunity, recent studies have suggested that TLR4 may play a broader role in mediating tissue inflammation and cell survival in response to noninfectious injury. We and other investigators have reported that cardiac TLR4 signaling is dynamically modulated in ischemic myocardium and that activation of TLR4 confers a survival benefit in the heart and in isolated cardiomyocytes. However, the signaling pathways leading to these effects are not completely understood. Here, we investigate the role of MyD88, an adaptor protein of TLR4 signaling, and inducible nitric oxide synthase (NOS2) in mediating TLR4-induced cardiomyocyte survival in an in vitro model of apoptosis. Serum deprivation induced a significant increase in the number of apoptotic cardiomyocytes as demonstrated by transferase-mediated dUTP nick-end labeling (TUNEL) assay, nuclear morphology, DNA laddering, and DNA-histone ELISA. Lipopolysaccharide (LPS), a TLR4 agonist, activated TLR4 signaling and led to significant reduction in apoptotic cardiomyocytes and improved cellular function of surviving cardiomyocytes with enhanced Ca2+ transients and cell shortening. We found that both TLR4 and MyD88 are required for the LPS-induced beneficial effects as demonstrated by improved survival and function in wild-type but not in TLR4(-/-) or MyD88(-/-) cardiomyocytes. Moreover, genetic deletion or pharmacological inhibition of NOS2 abolished survival and functional rescue of cardiomyocytes treated with LPS. Taken together, these data suggest that TLR4 protects cardiomyocytes from stress-induced injury through MyD88- and NOS2-dependent mechanisms. C1 Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Chao, W (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, GRJ-4-462,55 Fruit St, Boston, MA 02114 USA. EM wchao@partners.org FU NHLBI NIH HHS [HL-073363, HL-070896, HL-04336] NR 56 TC 38 Z9 40 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2006 VL 291 IS 4 BP H1900 EP H1909 DI 10.1152/ajpheart.00112.2006 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 084CP UT WOS:000240509700049 PM 16648192 ER PT J AU McClintock, DE Starcher, B Eisner, MD Thompson, BT Hayden, DL Church, GD Matthay, MA AF McClintock, Dana E. Starcher, Barry Eisner, Mark D. Thompson, B. Taylor Hayden, Doug L. Church, Gwynne D. Matthay, Michael A. CA National Heart Lung Blood Insti TI Higher urine desmosine levels are associated with mortality in patients with acute lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE acute respiratory distress syndrome; extracellular matrix; stretch injury ID OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; EXTRACELLULAR-MATRIX; CIGARETTE SMOKERS; CONTROLLED-TRIAL; CYSTIC-FIBROSIS; ELASTASE LOAD; EXCRETION; RADIOIMMUNOASSAY AB Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P = 0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/ kg predicted body weight group compared with the 6-ml/ kg predicted body weight group (P = 0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury. C1 Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Occupat & Environm Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Texas, Hlth Ctr, Dept Biochem, Tyler, TX USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA USA. Massachusetts Gen Hosp, Biostat Ctr, Boston, MA USA. RP McClintock, DE (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM dana.mcclintock@ucsf.edu OI Wiedemann, Herbert/0000-0002-4587-4401; Shanholtz, Carl/0000-0003-3938-178X FU NHLBI NIH HHS [R01 HL051856, N01HR46059, R37 HL051856-14, N01-HR-46059, P50-HL-74006, R01-HL-51856, R37 HL051856] NR 34 TC 30 Z9 32 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD OCT PY 2006 VL 291 IS 4 BP L566 EP L571 DI 10.1152/ajplung.00457.2005 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 082BF UT WOS:000240360800003 PM 16698854 ER PT J AU Yasumatsu, R Altiok, O Benarafa, C Yasumatsu, C Bingol-Karakoc, G Remold-O'Donnell, E Cataltepe, S AF Yasumatsu, Ryuji Altiok, Ozden Benarafa, Charaf Yasumatsu, Chie Bingol-Karakoc, Gulbin Remold-O'Donnell, Eileen Cataltepe, Sule TI SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE monocyte neutrophil elastase inhibitor; protease; serpin; premature ID SQUAMOUS-CELL CARCINOMA; CHRONIC LUNG-DISEASE; LOW-BIRTH-WEIGHT; PROTEINASE-INHIBITOR IMBALANCE; RESPIRATORY-DISTRESS SYNDROME; ALPHA-1-PROTEINASE INHIBITOR; PULMONARY INFLAMMATION; SERINE PROTEINASES; LEUKOCYTE ELASTASE; PREMATURE BABOONS AB Bronchopulmonary dysplasia (BPD) continues to be a major cause of morbidity in premature infants. An imbalance between neutrophil elastase and its inhibitors has been implicated in BPD. Serine protease inhibitor (SERPIN) B1 is an inhibitor of neutrophil proteases, including neutrophil elastase (NE) and cathepsin G (cat G). Recent studies suggest that SERPINB1 could provide protection in the airways by regulating excess protease activity associated with inflammatory lung disorders. In this study, we determined the distribution and ontogeny of SERPINB1 in the baboon lung and characterized the expression of SERPINB1 in baboon models of BPD. SERPINB1 expression was detected in the conducting airway and glandular epithelial cells in addition to neutrophils, macrophages, and mast cells. SERPINB1 mRNA and protein expression increased with advancing gestational age and in the new BPD model. In contrast, SERPINB1 expression levels were decreased in the old BPD model. Furthermore, SERPINB1 was detected as a high-molecular-mass (HMM) complex in lung tissue and bronchoalveolar lavage fluid samples from the BPD group. Analysis of the HMM complex by coimmunoprecipitation showed that these complexes were formed between SERPINB1 and NE or cat G. High-performance liquid chromatography (HPLC) ion trap mass spectrometry verified the presence of SERPINB1 in HMM complexes. Finally, NE activity level was compared between new and old baboon models of BPD and was found to be significantly lower in new BPD. Thus SERPINB1 upregulation in new BPD may be protective by contributing C1 Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Newborn Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, CBR Inst Biomed Res, Boston, MA USA. RP Cataltepe, S (reprint author), Childrens Hosp, Div Newborn Med, Enders 950,300 Longwood Ave, Boston, MA 02115 USA. EM sule.cataltepe@childrens.harvard.edu OI Benarafa, Charaf/0000-0002-2049-7769 FU NCRR NIH HHS [P510-RR-13986]; NHLBI NIH HHS [HL-66548, HL-04403, HL-075904, R01 HL066548] NR 54 TC 34 Z9 35 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD OCT PY 2006 VL 291 IS 4 BP L619 EP L627 DI 10.1152/ajplung.00507.2005 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 082BF UT WOS:000240360800010 PM 16617093 ER PT J AU Kobelt, P Goebel, M Stengel, A Schmidtmann, M van der Voort, IR Tebbe, JJ Veh, RW Klapp, BF Wiedenmann, B Wang, L Tache, Y Monnikes, H AF Kobelt, Peter Goebel, Miriam Stengel, Andreas Schmidtmann, Marco van der Voort, Ivo R. Tebbe, Johannes J. Veh, Ruediger W. Klapp, Burghard F. Wiedenmann, Bertram Wang, Lixin Tache, Yvette Moennikes, Hubert TI Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE c-fos; food intake ID CORTICOTROPIN-RELEASING-FACTOR; HYPOTHALAMIC ARCUATE NUCLEUS; GROWTH-HORMONE-SECRETION; AREA POSTREMA NUCLEUS; REDUCES FOOD-INTAKE; NEUROPEPTIDE-Y; RAT-BRAIN; SOLITARY TRACT; C-FOS; INTRAPERITONEAL INJECTION AB The interaction between ghrelin and bombesin or amylin administered intraperitoneally on food intake and brain neuronal activity was assessed by Fos-like immunoreactivity (FLI) in nonfasted rats. Ghrelin (13 mu g/kg ip) increased food intake compared with the vehicle group when measured at 30 min (g/kg: 3.66 +/- 0.80 vs. 1.68 +/- 0.42, P < 0.0087). Bombesin (8 mu g/kg) injected intraperitoneally with ghrelin (13 mu g/kg) blocked the orexigenic effect of ghrelin (1.18 +/- 0.41 g/kg, P < 0.0002). Bombesin alone (4 and 8 mu g/kg ip) exerted a dose-related nonsignificant reduction of food intake (g/kg: 1.08 +/- 0.44, P > 0.45 and 0.55 +/- 0.34, P > 0.16, respectively). By contrast, ghrelin-induced stimulation of food intake (g/kg: 3.96 +/- 0.56 g/kg vs. vehicle 0.82 +/- 0.59, P < 0.004) was not altered by amylin (1 and 5 mu g/kg ip) (g/kg: 4.37 +/- 1.12, P > 0.69, and 3.01 +/- 0.78, respectively, P > 0.37). Ghrelin increased the number of FLI-positive neurons/ section in the arcuate nucleus (ARC) compared with vehicle (median: 42 vs. 19, P < 0.008). Bombesin alone (4 and 8 mu g/kg ip) did not induce FLI neurons in the paraventricular nucleus of the hypothalamus (PVN) and coadministered with ghrelin did not alter ghrelin-induced FLI in the ARC. However, bombesin (8 mu g/kg) with ghrelin significantly increased neuronal activity in the PVN approximately threefold compared with vehicle and similar to 1.5-fold compared with the ghrelin group. Bombesin (8 mu g/kg) with ghrelin injected intraperitoneally induced Fos expression in 22.4 +/- 0.8% of CRF-immunoreactive neurons in the PVN. These results suggest that peripheral bombesin, unlike amylin, inhibits peripheral ghrelin induced food intake and enhances activation of CRF neurons in the PVN. C1 Free Univ Berlin, Dept Med, Div Hepatol Gastroenterol & Endocrinol, Charite,Fac Med, D-13353 Berlin, Germany. Free Univ Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, Charite, D-13353 Berlin, Germany. Free Univ Berlin, Inst Anat, Sect Electron Microscopy & Neuroanat, Charite, D-13353 Berlin, Germany. Univ Marburg, Dept Med, Div Gastroenterol & Endocrinol, Marburg, Germany. Univ Calif Los Angeles, Dept Med, Ctr Ulcer Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Educ Digest Dis Res Ctr, Ctr Neurol Sci,Digest Dis Div, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Monnikes, H (reprint author), Free Univ Berlin, Dept Med, Div Hepatol Gastroenterol & Endocrinol, Charite,Fac Med, Campus Virchow Klinikum,Augustenburger Pl 1, D-13353 Berlin, Germany. EM moennikes@web.de FU PHS HHS [R01 33061] NR 75 TC 14 Z9 14 U1 0 U2 0 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 OCT PY 2006 VL 291 IS 4 BP R903 EP R913 DI 10.1152/ajpregu.00681.2005 PG 11 WC Physiology SC Physiology GA 083LO UT WOS:000240457600007 PM 16644908 ER PT J AU Janech, MG Fitzgibbon, WR Ploth, DW Lacy, ER Miller, DH AF Janech, Michael G. Fitzgibbon, Wayne R. Ploth, David W. Lacy, Eric R. Miller, Donald H. TI Effect of low environmental salinity on plasma composition and renal function of the Atlantic stingray, a euryhaline elasmobranch SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE free water clearance; glomerular filtration rate; tubular urea reabsorption ID ACID-BASE-BALANCE; ST JOHNS RIVER; FRESH-WATER; SCYLIORHINUS-CANICULA; SQUALUS-ACANTHIAS; DASYATIS-SABINA; RAJA-ERINACEA; CARCHARHINUS-LEUCAS; UREA REABSORPTION; EXTERNAL MEDIUM AB Marine elasmobranchs maintain internal osmolality higher than their external environment, resulting in an osmotic gradient for branchial water uptake. This gradient is markedly increased in low-salinity habitats. The subsequent increase in water uptake presents a challenge to volume homeostasis. The Atlantic stingray is a marine elasmobranch that inhabits a remarkable range of environmental salinities. We hypothesized that the ability of these stingrays to regulate fluid volume in low-salinity environments is due primarily to a renal glomerular and tubular functional reserve. We tested this hypothesis by measuring renal excretory function after a rapid and sustained 50% reduction in the osmolality of the external medium. Atlantic stingrays were maintained in harbor water [control salinity (CS) similar to 850 mosmol/kgH(2)O] for 1 wk. Rays were then either transferred to diluted harbor water [low salinity (LS) similar to 440 mosmol/kgH(2)O] or maintained in CS for a further 24 h. Renal excretory function was markedly higher in the rays subjected to low salinity. Glomerular filtration rate was threefold higher and urine flow rate ninefold higher in the LS group. The clearance of solute-free water was greater, and solute-free water comprised a significantly larger proportion of the urine output for the stingrays transferred to dilute harbor water. We conclude that 1) the kidneys of Atlantic stingrays have a remarkable glomerular and tubular functional reserve, and 2) the marked increase in renal function attenuates the increase in fluid volume when these fish move into low-salinity habitats. C1 Med Univ S Carolina, Coll Charleston, Dept Med, Div Nephrol,Grice Marine Lab, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Fitzgibbon, WR (reprint author), Med Univ S Carolina, Coll Charleston, Dept Med, Div Nephrol,Grice Marine Lab, Charleston, SC 29425 USA. EM fitzgiwr@musc.edu OI Janech, Michael/0000-0002-3202-4811 NR 57 TC 9 Z9 10 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2006 VL 291 IS 4 BP F770 EP F780 DI 10.1152/ajprenal.00026.2006 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 081JD UT WOS:000240313000008 PM 16609153 ER PT J AU Faraone, SV Biederman, J Spencer, T Mick, E Murray, K Petty, C Adamson, JJ Monuteaux, MC AF Faraone, Stephen V. Biederman, Joseph Spencer, Thomas Mick, Eric Murray, Kate Petty, Carter Adamson, Joel J. Monuteaux, Michael C. TI Diagnosing adult attention deficit hyperactivity disorder: Are late onset and subthreshold diagnoses valid? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; SYMPTOMS; ADHD; COMORBIDITY; CHILDREN; DEFINITION; CRITERION; IMPACT AB Objective: Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish an onset before the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve DSM's diagnosis threshold. Method: The authors addressed the validity of DSM-IV's age-at-onset and symptom threshold criteria by comparing four groups of adults: 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria. The authors hypothesized that subjects with late-onset and subthreshold ADHD would show patterns of psychiatric comorbidity, functional impairment, and familial transmission similar to those seen in subjects with full ADHD. Results: Subjects with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Most children with late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and showed a different pattern of familial transmission than the other forms of ADHD. Conclusions: The data about the clinical features of probands and the pattern of transmission of ADHD among relatives found little evidence for the validity of subthreshold ADHD among such subjects, who reported a lifetime history of some symptoms that never met DSM-IV's threshold for diagnosis. In contrast, the results suggested that late-onset adult ADHD is valid and that DSM-IV's age-at-onset criterion is too stringent. C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01-MH-57934] NR 31 TC 182 Z9 184 U1 0 U2 7 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 OCT PY 2006 VL 163 IS 10 BP 1720 EP 1729 DI 10.1176/appi.ajp.163.10.1720 PG 10 WC Psychiatry SC Psychiatry GA 089UN UT WOS:000240906800015 PM 17012682 ER PT J AU Biederman, J Petty, C Fried, R Fontanella, J Doyle, AE Seidman, LJ Faraone, SV AF Biederman, Joseph Petty, Carter Fried, Ronna Fontanella, Jessie Doyle, Alysa E. Seidman, Larry J. Faraone, Stephen V. TI Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; ADHD; CHILDREN; PERFORMANCE; NEUROPSYCHOLOGY; SIBLINGS AB Objective: The association between deficits in executive functioning and functional outcomes was examined among adults with attention deficit hyperactivity disorder (ADHD). Method: Subjects were adults who did (N = 213) and did not (N = 145) meet DSM-IV criteria for ADHD. The authors defined having deficits in executive functioning as having at least two measures of executive functioning with scores 1.5 standard deviations below those of matched comparison subjects. Results: Significantly more adults with ADHD had deficits of executive functioning than comparison subjects. Deficits of executive functioning were associated with lower academic achievement, irrespective of ADHD status. Subjects with ADHD with deficits of executive functioning had a significantly lower socioeconomic status and a significant functional morbidity beyond the diagnosis of ADHD alone. Conclusions: Psychometrically defined deficits of executive functioning may help identify a subgroup of adults with ADHD at high risk for occupational and academic underachievement. More efforts are needed to identify cost-effective approaches to screen individuals with ADHD for deficits of executive functioning. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Syracuse, Dept Psychiat, Upstate Med Univ, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, 32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01-MH-57934] NR 39 TC 103 Z9 107 U1 1 U2 11 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 OCT PY 2006 VL 163 IS 10 BP 1730 EP 1738 DI 10.1176/appi.ajp.163.10.1730 PG 9 WC Psychiatry SC Psychiatry GA 089UN UT WOS:000240906800016 PM 17012683 ER PT J AU Haroutunian, V Katsel, P Dracheva, S Davis, KL AF Haroutunian, Vahram Katsel, Pavel Dracheva, Stella Davis, Kenneth L. TI The human homolog of the QKI gene affected in the severe dysmyelination "quaking" mouse phenotype: Downregulated in multiple brain regions in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BINDING PROTEINS; MESSENGER-RNA; MUTANT MICE; EXPRESSION; MYELIN; DYSFUNCTION AB Objective: The authors sought to understand the origins of oligodendrocyte/ myelin gene expression abnormalities in the brains of persons with schizophrenia. Method: Twelve cortical regions ( Brodmann's areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7, and 17) and three non-cortical regions ( caudate, hippocampus, and putamen) of 16 elderly schizophrenia patients and 14 matched comparison subjects were examined using 450 separate microarrays. The mRNA levels of QKI and its isoforms were then measured in a larger cohort by using quantitative real-time polymerase chain reaction (qPCR) in the cingulate cortex of schizophrenia subjects and matched comparison subjects. Results: Expression of QKI mRNA was decreased in seven cortical regions and the hippocampus in the schizophrenia subjects. QKI gene expression deficits detected by microarray were validated by qPCR in the cingulate cortex, where the expression of isoforms QKI-5, QKI-6, and QKI-7 were profoundly perturbed in schizophrenia. Conclusions: Since QKI plays a fundamental role in oligodendrocyte differentiation and in myelination, its underexpression may be pivotal to, and upstream of, other myelin-associated gene expression abnormalities in schizophrenia. Given the role of QKI in determination of oligodendrocyte fate, these results not only confirm oligodendrocyte-related gene expression abnormalities in schizophrenia but suggest that the physiology of glial progenitor cells may be altered in schizophrenia. C1 Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, Bronx, NY USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, Dept Psychiat, Rm 4F-33A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [MH-064673, MH-45212] NR 12 TC 62 Z9 62 U1 0 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 OCT PY 2006 VL 163 IS 10 BP 1834 EP 1837 DI 10.1176/appi.ajp.163.10.1834 PG 4 WC Psychiatry SC Psychiatry GA 089UN UT WOS:000240906800032 PM 17012699 ER PT J AU Benacerraf, BR AF Benacerraf, Beryl R. TI Inversion mode display of 3D sonography: Applications in obstetric and gynecologic imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE 3D sonography; pelvic imaging; sonography; volume imaging; women's imaging AB OBJECTIVE. Three-dimensional sonography involves volume acquisitions of sonographic data that can be displayed in a variety of ways, including surface rendering and multiplanar reconstruction. A new method of displaying sonographic volumes is called the inversion mode, which displays the cystic portions within the entire volume as echogenic areas. The gray-scale portion of the image becomes transparent, and the cystic areas become brightly visible in three dimensions. CONCLUSION. This article shows the applications for this method of volume sonography display and shows the importance of being able to visualize all of the cystic areas concurrently within a volume. C1 Diagnost Ultrasound Assoc, PC, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Assoc, PC, 333 Longwood Ave,Ste 400, Boston, MA 02115 USA. NR 5 TC 17 Z9 17 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 OCT PY 2006 VL 187 IS 4 BP 965 EP 971 DI 10.2214/AJR.05.1462 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 088EL UT WOS:000240794200024 PM 16985144 ER PT J AU Irrgang, JJ Anderson, AF Boland, AL Harner, CD Neyret, P Richmond, JC Shelbourne, KD AF Irrgang, James J. Anderson, Allen F. Boland, Arthur L. Harner, Christopher D. Neyret, Philippe Richmond, John C. Shelbourne, K. Donald CA Int Knee Documentation Comm TI Responsiveness of the International Knee Documentation Committee Subjective Knee Form SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE knee; patient-oriented outcomes; responsiveness ID HEALTH-STATUS; INDEX; PAIN AB Background and Purpose: The International Knee Documentation Committee Subjective Knee Form was developed to measure change in symptoms, function, and sports activity in patients treated for a variety of knee conditions. Although previous research has demonstrated reliability and validity of the form, its responsiveness has not been evaluated. The purpose of this study was to determine responsiveness of the International Knee Documentation Committee Subjective Knee Form. Study Design: Cohort study (diagnosis); Level of evidence, 1. Methods: Patients who participated in the original validation study for the International Knee Documentation Committee Subjective Knee Form completed the form and a 7-level global rating of change scale that ranged from greatly worse to greatly better after a mean of 1.6 years (range, 0.5-2.3 years). Analyses included calculation of the standardized response mean and mean change in International Knee Documentation Committee Subjective Knee Form score compared to the patient's perception of change on the global rating of change scale. In addition, a receiver operating characteristic curve was plotted to determine the change in score that best distinguished patients who improved from those who did not. Results: The overall standardized response mean was 0.94, which is considered large. With the exception of those who were slightly worse or unchanged, the mean change in the International Knee Documentation Committee Subjective Knee Form score compared to the patients' perceived global ratings of change was as expected (greatly worse, -15.1; somewhat worse, -8.4; slightly worse, 20.6; no change, 10.7; slightly better, 5.9; somewhat better, 18.1; greatly better, 38.7). The receiver operating characteristic curve analysis revealed that a change score of 11.5 points had the highest sensitivity, and a change score of 20.5 points had the highest specificity to distinguish between those who were or were not improved. Conclusion: The International Knee Documentation Committee Subjective Knee Form is a responsive measure of symptoms, function, and sports activity for patients with a variety of knee conditions. C1 Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tennessee Orthopaed Alliance, Nashville, TN USA. Univ Pittsburgh, Med Ctr Sports Med, Pittsburgh, PA 15213 USA. Hosp Crois Rousse, Lyon Caluire, France. New England Baptist Hosp, Boston, MA USA. Methodist Sports Med Ctr, Indianapolis, IN USA. RP Irrgang, JJ (reprint author), Univ Pittsburgh, Dept Orthopaed Surg, ATC,Room 911,Kaufman Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jirrgang@pitt.edu NR 16 TC 131 Z9 132 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD OCT PY 2006 VL 34 IS 10 BP 1567 EP 1573 DI 10.1177/0363546506288855 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 088TG UT WOS:000240833400002 PM 16870824 ER PT J AU Almyroudis, NG Sutton, DA Linden, P Rinaldi, MG Fung, J Kusne, S AF Almyroudis, N. G. Sutton, D. A. Linden, P. Rinaldi, M. G. Fung, J. Kusne, S. TI Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE mould; mucorales; solid organ transplantation; zygomycosis ID INVASIVE GASTROINTESTINAL ZYGOMYCOSIS; CARDIAC ALLOGRAFT RECIPIENT; CARE CANCER CENTER; PULMONARY MUCORMYCOSIS; FUNGAL-INFECTIONS; RENAL-TRANSPLANTATION; RHINOCEREBRAL MUCORMYCOSIS; LIVER-TRANSPLANTATION; AMPHOTERICIN-B; CUNNINGHAMELLA-BERTHOLLETIAE AB Zygomycetes are ubiquitous fungi that can cause invasive disease associated with high mortality. We report 10 solid organ transplant recipients with zygomycosis (incidence 2 per 1000) and reviewed 106 cases in the English-language literature. These included renal (n = 73), heart (n = 16), lung (n = 4), heart/lung (n = 2), liver (n = 19) and kidney/pancreas (n = 2) transplant recipients. All patients were receiving immunosuppression and the vast majority steroids. The clinical presentation included rhino-sino-orbital (n = 20), rhinocerebral (n = 16), pulmonary (n = 28), gastrointestinal (n = 13), cutaneous (n = 18), renal (n = 6) and disseminated disease (n = 15). Most frequently isolated genera were Rhizopus (73%) followed by Mucor (13%). The overall mortality was 49%. While rhino-sino-orbital disease had the best prognosis, rhinocerebral disease had high mortality (93%) comparable to disseminated disease. A favorable outcome was associated with limited, surgically accessible disease and early surgical intervention along with amphotericin B administration. C1 Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Dept Crit Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Dept Surg, Pittsburgh, PA USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Linden, P (reprint author), Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Dept Crit Care, Pittsburgh, PA 15260 USA. EM lindenpk@ccm.upmc.edu; Kusne.shimon@mayo.edu RI Fung, John/A-2679-2012 NR 104 TC 111 Z9 115 U1 0 U2 0 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 OCT PY 2006 VL 6 IS 10 BP 2365 EP 2374 DI 10.1111/j.1600-6143.2006.01496.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 082DD UT WOS:000240366000018 PM 16925570 ER PT J AU Mashour, GA AF Mashour, George A. TI Integrating the science of consciousness and anesthesia SO ANESTHESIA AND ANALGESIA LA English DT Review ID CORTICAL AREA MT; SEVOFLURANE ANESTHESIA; VEGETATIVE STATE; SPINAL-CORD; GENERAL-ANESTHETICS; BRAIN ACTIVITY; VISUAL-CORTEX; NITROUS-OXIDE; NEURONS; CONNECTIVITY AB The nature and mechanism of human consciousness is emerging as one of the most important scientific and philosophical questions of the 21(st) century. Disregarded as a subject of serious inquiry throughout most of the 20(th) century, it has now regained legitimacy as a scientific endeavor. The investigation of consciousness and the mechanisms of general anesthesia have begun to converge. In the present article I provide an introduction to the study of consciousness, describe the neural correlates of consciousness that may be targets of general anesthetics, and suggest an integrated approach to the science of consciousness and anesthesia. C1 Harvard Univ, Dept Anesthesia, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mashour, GA (reprint author), Harvard Univ, Dept Anesthesia, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM gmashour@partners.org NR 75 TC 59 Z9 59 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 2006 VL 103 IS 4 BP 975 EP 982 DI 10.1213/01.ane.0000232442.69757.4a PG 8 WC Anesthesiology SC Anesthesiology GA 087RL UT WOS:000240759800034 PM 17000815 ER PT J AU Goldhaber-Fiebert, S Grecu, L AF Goldhaber-Fiebert, Sara Grecu, Loreta TI Postoperative ST-segment elevation: was vasospasm caused by anaphylaxis or by its treatment with epinephrine? SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID CORONARY-ARTERY SPASM; MYOCARDIAL-INFARCTION; PATIENT; ANGINA AB Background: Anaphylaxis must be recognized and treated promptly to avoid significant morbidity and mortality. In this clinical setting, electrocardiographic changes can be multifactorial. Objective: To discuss vasospasm as a cause of myocardial ischemia and its possible triggering by anaphylaxis itself or by the administration of epinephrine. Methods: We describe a patient with multiple previous allergies who received intravenous epinephrine to treat suspected anaphylaxis. She immediately developed crushing chest pain with ST-segment elevations in the inferior leads. Throughout the discussion, we address differential diagnoses, physiologic features, and treatment. Results: Her symptoms and electrocardiographic changes were consistent with vasospasm, which resolved after treatment with sublingual nitroglycerin. However, the reaction was sufficient to cause an elevation in the troponin T level and, therefore, myocardial damage on the cellular level. Conclusions: Cardiovascular complications, including electrocardiographic changes, may be induced by anaphylactic mediators or by medications used for its treatment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Grecu, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM lgrecu@partners.org NR 20 TC 5 Z9 5 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. 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RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 39 BP S13 EP S13 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400040 ER PT J AU Camargo, CJ Ahn, C Clark, S Sullivan, AF AF Camargo, C. A., Jr. Ahn, C. Clark, S. Sullivan, A. F. TI Current status of US emergency departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 388 BP S116 EP S116 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400387 ER PT J AU Fix, ML Listwa, TM Nelson, SW Goldstein, JN Thomas, SH AF Fix, M. L. Listwa, T. M. Nelson, S. W. Goldstein, J. N. Thomas, S. H. TI Comparison of a radial artery compression device with invasive radial artery blood pressure monitoring SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 220 BP S68 EP S68 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400223 ER PT J AU Levine, M Thomas, S Geib, A Thomsen, T Pozner, C AF Levine, M. Thomas, S. Geib, A. Thomsen, T. Pozner, C. TI Serum glucose concentrations as a marker of severity in calcium channel blocker overdose SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Mt Auburn Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 262 BP S80 EP S80 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400264 ER PT J AU Manini, AF McAfee, AT Noble, VE Bohan, JS AF Manini, A. F. McAfee, A. T. Noble, V. E. Bohan, J. S. TI Risk stratification of emergency department patients with chest pain using C-reactive protein SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Harvard Affiliated Emergency Med Residency, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 89 BP S28 EP S28 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400090 ER EF