FN Thomson Reuters Web of Science™ VR 1.0 PT J AU De Bazelaire, C Rofsky, NM Duhamel, G Michaelson, MD George, D Alsop, DC AF De Bazelaire, C Rofsky, NM Duhamel, G Michaelson, MD George, D Alsop, DC TI Arterial spin labeling blood flow magnetic resonance imaging for the characterization of metastatic renal cell carcinoma SO ACADEMIC RADIOLOGY LA English DT Article DE MRI; arterial spin labelling; renal cell carcinoma; antiangiogenesis; blood flow ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; INVERSION-RECOVERY; LUNG-CANCER; PERFUSION; BRAIN; TUMOR; SIGNAL; WATER; ANGIOGENESIS AB Rationale and Objective. This study sought to assess the feasibility of arterial spin labeling (ASL) blood flow (BF) magnetic resonance imaging (MRI) for the study of metastatic renal cell carcinoma (RCC) in the body, where the respiratory, cardiac, and peristaltic motions present challenges when applying ASL. Materials and Methods. ASL was performed using a background-suppressed single-section flow-alternating inversion recovery (FAIR) preparation and a single-shot fast spin-echo imaging sequence on a 3.0-T whole body imager. Tumor BF was evaluated for 26 patients with RCC metastatic to the liver, bone, lung, or lymph nodes before VEGF receptor,inhibitor therapy. Two cases with tumor size change after treatment were also scanned I month after therapy. For validation, kidney cortex BF in five normal volunteers was measured with the same technique and compared with literature values. Results. ASL was successfully performed in all normal volunteers and in 20 of 26 patients. The six failures resulted from a systematic error, which can be avoided in future studies. For normal volunteers, measured kidney cortex BF was 275 14 mL/min/100 g, a value consistent with the literature. ASL determined tumor BF averaged across tumor volume and subjects was 194 mL/min/100 g (intersubject SD = 100), resulting in high perfusion signal and conspicuity of lesions. Bright signal was also seen in large vessels and occasionally in bowel. In the two cases studied I month after therapy, ASL perfusion changes were consistent with tumor size changes. Conclusion. With background suppression, ASL MRI is a feasible method for quantifying BF in patients with renal cell carcinoma. This technique may be useful for evaluating tumor response to antiangiogenic agents. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RP Alsop, DC (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM dalsop@bidmc.harvard.edu RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 NR 39 TC 76 Z9 76 U1 1 U2 6 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2005 VL 12 IS 3 BP 347 EP 357 DI 10.1016/j.acra.2004.12.012 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 907GK UT WOS:000227703800012 PM 15766695 ER PT J AU Elkashef, A Holmes, TH Bloch, DA Shoptaw, S Kampman, K Reid, MS Somoza, ER Ciraulo, D Rotrosen, J Leiderman, D Montgomery, A Vocci, F AF Elkashef, A Holmes, TH Bloch, DA Shoptaw, S Kampman, K Reid, MS Somoza, ER Ciraulo, D Rotrosen, J Leiderman, D Montgomery, A Vocci, F TI Retrospective analyses of pooled data from CREST I and CREST II trials for treatment of cocaine dependence SO ADDICTION LA English DT Article DE cocaine; pharmacotherapy; statistics ID INTERVIEW GUIDE; RATING-SCALE; SUCCESS; ABUSE AB Aim To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial (CREST). Pooling data from these small pilot trials into four major drug classes permitted data exploration for treatment and covariate effects with increased sample size. Design Small pilot trials were conducted to screen fifteen medications as prospective treatments for cocaine dependence. Studies included a flexible 2-week to 4-week screening/baseline period followed by an 8-week randomized treatment condition. Participants were randomized equally to one of up to three active medications or placebo. Setting Five Medications Development Research Units at the five academic centers of University of Cincinnati, New York University, University of Pennsylvania, University of California Los Angeles and Boston University. Participants The pooled data set consisted of 3 5 7 total subjects. Standardized inclusion and exclusion criteria were employed in subject selection to enhance consistency of cocaine-dependent study participants across all sites (see reports on individual trials in this supplement for details). All participants provided at least two urine samples that were positive for cocaine metabolite during a two-week period prior to being randomized. Intervention All subjects in these trials, those randomized to placebo and active medications, received active treatment in the form of evidence-based cognitive behavioral therapy. Measures Quantitative urine benzoylecgonine (BE), self-report of cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared between each class of medication and its matched-placebo group. Findings Regression analysis of pooled data did not identify any statistically significant differences between treatment and matched-placebo for any of the four classes. Exploration of the effects of baseline covariates indicated that gender and African American status were associated significantly with outcome. Female gender was consistently associated with poorer outcomes for medication and placebo groups, while the direction of association between African American status and outcome differed by treatment groups. Retention was also examined: dropout rates may have been somewhat higher for placebo than treatment. groups during the early active-treatment period. Classification trees were used to identify characteristics of subjects who were abstinent for at least two weeks during the eight-week trial; only 4.0% of females while 17.9% of males achieved this criterion. Conclusions Results presented here may prove useful for planning future clinical trials for therapies targeting cocaine dependence. C1 Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Biostat, Stanford, CA 94305 USA. NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Calif Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA USA. Friends Res Inst Inc, Los Angeles, CA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NYU, Sch Med, New York, NY USA. VA New York Harbor Healthcare Syst, Dept Psychiat, New York, NY USA. Cincinnati VA Med Ctr, Cincinnati, OH USA. Univ Cincinnati, Coll Med, CinARC, Cincinnati, OH USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, MDRU, Boston, MA 02118 USA. RP Holmes, TH (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Biostat, HRP Redwood Bldg, Stanford, CA 94305 USA. EM tholmes@stanford.edu FU NIDA NIH HHS [1 Y01 DA 50038] NR 19 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2005 VL 100 SU 1 BP 91 EP 101 DI 10.1111/j.1360-0443.2005.00986.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 907PB UT WOS:000227729200009 PM 15730353 ER PT J AU Kampman, KM Leiderman, D Holmes, T LoCastro, J Bloch, DA Reid, MS Shoptaw, S Montgomery, MA Winhusen, TM Somoza, EC Ciraulo, DA Elkashef, A Vocci, F AF Kampman, KM Leiderman, D Holmes, T LoCastro, J Bloch, DA Reid, MS Shoptaw, S Montgomery, MA Winhusen, TM Somoza, EC Ciraulo, DA Elkashef, A Vocci, F TI Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned SO ADDICTION LA English DT Article DE clinical trial; cocaine; pharmacotherapy ID DEPENDENCE; FLUOXETINE; THERAPY; ABUSERS AB Aims The Cocaine Rapid Efficacy Screening Trials (CREST) were designed by the National Institute on Drug Abuse Division of Treatment Research and Development (NIDA, DT RAD) to rapidly screen a number of medications potentially useful for the treatment of cocaine dependence. Design, Each CREST trial was designed to compare several medications in a single trial against an unmatched placebo. The placebo group was included in each trial to avoid the nearly universal positive response to medications seen in open-label trials. In addition, a common set of procedures and outcome measures were employed throughout to increase comparability of results obtained from different trials and from different times. Participants In all, 18 medications were screened in seven different trials, conducted in four different sites throughout the United States involving 398 cocaine-dependent patients. Findings Three medications were found to be promising enough to include in subsequent larger trials. Common statistical procedures for evaluating medications were developed to facilitate comparisons across sites and across time. A portion of the data were pooled and analyzed, which yielded some useful insights into cocaine dependence and its treatment. Finally, a review of individual trials together with the pooled analysis revealed several potential improvements for future screening trials. Conclusions Overall, the CREST trials proved to be useful for rapidly screening medications for treatment of cocaine dependence, but several modifications in design should be made before this framework is applied further. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Natl Inst Drug Abuse, Medicat Dev Div, Bethesda, MD USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, MDRU, Boston, MA USA. VA Med Ctr, Cincinnati VA UC NIDA MDRU, Cincinnati, OH USA. Univ Cincinnati, Coll Med, CinARC, Cincinnati, OH USA. NYU, Sch Med, New York, NY USA. VA New York Harbor Healthcare Syst, Dept Psychiat, New York, NY USA. Stanford Univ, Sch Med, Dept Hlth Res, Stanford, CA USA. Stanford Univ, Sch Med, Policy Div Biostat, Stanford, CA USA. Univ Calif Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA USA. Friends Res Inst Inc, Los Angeles, CA USA. RP Kampman, KM (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM kampman_k@mail.trc.upenn.edu OI Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [Y01 DA 30012] NR 14 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2005 VL 100 SU 1 BP 102 EP 110 DI 10.1111/j.1360-0443.2005.00987.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 907PB UT WOS:000227729200010 PM 15730354 ER PT J AU Vaillant, G AF Vaillant, G TI Secrets and lies: Comments on Dawson et al. SO ADDICTION LA English DT Editorial Material ID ALCOHOLICS C1 Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. RP Vaillant, G (reprint author), Brigham & Womens Hosp, Div Psychiat, 75 Francis St, Boston, MA 02115 USA. EM gvaillant@partners.or NR 3 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2005 VL 100 IS 3 BP 294 EP 294 DI 10.1111/j.1360-0443.2005.01018.x PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 902RJ UT WOS:000227373900007 PM 15733239 ER PT J AU Shipherd, JC Stafford, J Tanner, LR AF Shipherd, JC Stafford, J Tanner, LR TI Predicting alcohol and drug abuse in Persian Gulf War veterans: What role do PTSD symptoms play? SO ADDICTIVE BEHAVIORS LA English DT Article DE substance abuse; posttraumatic stress disorder; veterans ID POSTTRAUMATIC-STRESS-DISORDER; SCREENING-TEST AB This study is a prospective longitudinal examination of symptoms of drug and alcohol use (SUD) and PTSD symptoms in 1006 veterans in the 6 years (T3) following return from the Persian Gulf War (PGW). Both alcohol and drug use at T3 were significantly correlated with demographic variables and all three types of PTSD symptoms (reexperiencing, avoidance, and arousal) as measured at T2. Hierarchical regressions were conducted to examine the self-medication hypothesis, which was supported for drug use but not for alcohol use at T3. (c) 2004 Elsevier Ltd. All rights reserved. C1 Vet Adm Med Ctr Jamaica Plain, VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Shipherd, JC (reprint author), Vet Adm Med Ctr Jamaica Plain, VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM Jillian.Shipherd@med.va.gov NR 8 TC 51 Z9 53 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAR PY 2005 VL 30 IS 3 BP 595 EP 599 DI 10.1016/j.addbeh.2004.07.004 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 904XT UT WOS:000227532600021 PM 15718078 ER PT J AU Cully, JA Molinari, VA Snow, AL Burruss, J Kotrla, KJ Kunik, ME AF Cully, JA Molinari, VA Snow, AL Burruss, J Kotrla, KJ Kunik, ME TI Utilization of emergency center services by older adults with a psychiatric diagnosis SO AGING & MENTAL HEALTH LA English DT Article ID CONSULTATIONS AB Information regarding older adult emergency center (EC) patient characteristics remains limited, despite its increasing importance in health care delivery systems. This retrospective study encompasses all EC visits over an eight-year period (n = 825,682) to a large urban county hospital. Only participants with a primary psychiatric diagnosis were examined, and included a total of 53,894 adults, 18-64 years old and 1,478 adults, >= 65 years old. Despite an increasing aging population, EC visits for older adults with psychiatric disorders did not increase over time. Within the older adult sample, cognitive, psychotic, and bipolar disorders were associated with higher rates of admission to the hospital, while substance use, depressive, and anxiety disorders were associated with lower numbers of inpatient admissions. African-Americans were overrepresented in the EC and admitted to the hospital at higher rates, compared to other ethnic groups. Caucasian patients were the group most frequently diagnosed with a substance use disorder. In conclusion, differences in race, and diagnosis support the idea that such variables directly relate to utilization rates, presentation, and disposition within the EC. C1 Michael E DeBakey Vet Affairs Med Ctr, Vet Affairs HSR&D Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ S Florida, Louis de la Parte Florida Mental Hlth Inst, Dept Aging & Mental Hlth, Tampa, FL 33620 USA. Texas A&M Coll Med, Dept Psychiat & Behav Sci, Temple, TX USA. Cent Texas Vet Hlth Care Syst, Temple, TX USA. RP Cully, JA (reprint author), 2002 Holcombe 152, Houston, TX 77030 USA. EM jcully@bcm.tmc.edu NR 13 TC 6 Z9 6 U1 0 U2 2 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD MAR PY 2005 VL 9 IS 2 BP 172 EP 176 DI 10.1080/13607860412331336779 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 915AB UT WOS:000228268900012 PM 15804636 ER PT J AU Behler, C Shade, S Gregory, K Abrams, D Volberding, P AF Behler, C Shade, S Gregory, K Abrams, D Volberding, P TI Anemia and HIV in the antiretroviral era: Potential significance of testosterone SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-OF-LIFE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; HUMAN-BONE MARROW; INFECTED PATIENTS; TREATMENT OPTIONS; CHRONIC DISEASE; AIDS PATIENTS; THERAPY; MEN AB Anemia, the most common hematological disorder in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), is associated with decreased quality of life and survival. Hypogonadism is prevalent in advanced HIV disease, however, low testosterone levels have not been customarily implicated in HIV-associated anemia. This study was undertaken to determine whether there is a relationship between testosterone levels and androgen use with anemia in HIV, and to characterize other clinical correlates of HIV-associated anemia. This was a cross-sectional, observational study of 200 HIV-positive patients at a public hospital HIV clinic from July 2000 to August 2001. A written questionnaire detailed previous and current medication use, opportunistic infections, and malignancies. Hematological and virological parameters, testosterone, and erythropoietin levels were measured; CD4(+) T lymphocyte count and viral load nadir and peak levels were obtained from the computerized medical record. Anemia was defined as hemoglobin <13.5 g/dl in men and <11.6 g/dl in women. Twenty-four percent of women and 28% of men were anemic. Anemia was associated with lymphopenia (adjusted OR 4.0, 95% CI 1.36-11.80), high erythropoietin levels (adjusted OR 7.73, 95% CI 2.92-20.48), and low testosterone levels (adjusted OR 3.27, 95% CI 1.01-10.60). Anemia was negatively associated with female sex (adjusted OR 0.30, 95% CI 0.11-0.85), current antiretroviral therapy (adjusted OR 0.43, 95% CI 0.20-0.95), current androgen use (adjusted OR 0.20, 95% CI 0.05-0.84), and macrocytosis (adjusted OR 0.23, 95% CI 0.09-0.61). Low testosterone levels may have a positive association and supplemental androgens a negative association with anemia in HIV disease. C1 Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94143 USA. RP Behler, C (reprint author), Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, Box 0654, San Francisco, CA 94143 USA. EM behlerc@itsa.ucsf.edu FU NIAID NIH HHS [P30 AI 27763-11] NR 35 TC 4 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2005 VL 21 IS 3 BP 200 EP 206 DI 10.1089/aid.2005.21.200 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 913WT UT WOS:000228187000002 PM 15795525 ER PT J AU Wayne, PM Scarborough, DM Krebs, DE Parker, SW Wolf, SL Asmundson, L McGibbon, CA AF Wayne, PM Scarborough, DM Krebs, DE Parker, SW Wolf, SL Asmundson, L McGibbon, CA TI Tai Chi for vestibulopathic balance dysfunction: A case study SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Article ID QUALITY-OF-LIFE; VESTIBULAR REHABILITATION; CONTROLLED-TRIAL; OLDER ADULTS; EXERCISE; STABILITY; OUTCOMES; HISTORY C1 New England Sch Acupuncture, Dept Res, Watertown, MA USA. Fac Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA USA. MGH Biomot Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MGH, Otoneurol & Gait Balance Disorder Unit, Dept Neurol, Boston, MA USA. Emory Univ, Sch Med, Dept Rehabil Med, Ctr Res Complementary & Alternat Med Neurodegener, Atlanta, GA 30322 USA. RP Wayne, PM (reprint author), New England Sch Acupuncture, Dept Res, Watertown, MA USA. RI Wolf, Steven/F-6588-2010 OI Wolf, Steven/0000-0002-9446-8995 FU NCCIH NIH HHS [R21AT00553] NR 43 TC 5 Z9 6 U1 0 U2 3 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD MAR-APR PY 2005 VL 11 IS 2 BP 60 EP 66 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 906GI UT WOS:000227628300006 PM 15819449 ER PT J AU Schwartz, GG AF Schwartz, GG TI Statins in acute coronary syndromes: The sooner, the better? SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID C-REACTIVE PROTEIN; AVERAGE CHOLESTEROL LEVELS; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; CONTROLLED TRIAL; HEART-DISEASE; SIMVASTATIN; PRAVASTATIN; EVENTS; INFLAMMATION C1 VA Med Ctr, Cardiol Sect, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM gregory.schwartz@med.va.gov NR 26 TC 0 Z9 0 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 MAR PY 2005 VL 149 IS 3 BP 377 EP 380 DI 10.1016/j.ahj.2004.09.043 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 917RV UT WOS:000228487800001 PM 15864223 ER PT J AU Smith, CS Cannon, CP McCabe, CH Murphy, SA Bentley, J Braunwald, E AF Smith, CS Cannon, CP McCabe, CH Murphy, SA Bentley, J Braunwald, E TI Acute Ischemic Heart Disease - Early initiation of lipid-lowering therapy for acute coronary syndromes improves compliance with guideline recommendations: Observations from the Orbofiban in Patients with Unstable Coronary Syndromes (OPUS-TIMI 16) trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ARTERY-DISEASE; SECONDARY PREVENTION; NATIONAL REGISTRY; AMERICAN-COLLEGE; UNITED-STATES; CHOLESTEROL; CARE; HYPERLIPIDEMIA; UNDERTREATMENT AB Background Lipid-lowering is effective in the prevention of cardiovascular morbidity and mortality in patients with coronary artery disease, but effective strategies for improving the implementation of these therapies are needed. Methods In the 10 288 patients in the OPUS-TIMI 16 trial, patients were stratified by use of lipid-lowering therapy during index hospitalization and were compared for use of lipid-lowering therapy at follow-up as well as for clinical outcomes. Results Lipid-lowering therapy was used in 38% of patients during the index hospitalization, of which 94% were statins. At 10 months, 88% of patients who were discharged on lipid-lowering medications remained on these drugs. Conversely, only 34% of patients not discharged on lipid-lowering medications were receiving them at 10 months. Forty-one percent of patients with prior history of hyperlipidemia requiring treatment were not discharged on lipid-lowering therapy, and of these, only 51% were subsequently started on a lipid-lowering medication as an outpatient despite clear indications. Patients treated as inpatients with lipid-lowering therapy had a lower mortality rate at 10 months adjusted by propensity analysis (3.1% vs 5.1%, P <.0001) than patients not treated with lipid-lowering therapy. Conclusion In patients with acute coronary syndromes, the initiation of lipid-lowering therapy in the inpatient setting increases the rate of its subsequent use at 10 months, making this an important method of ensuring appropriate secondary prevention. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Nottingham Clin Res Grp, Nottingham, England. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 34 TC 25 Z9 27 U1 0 U2 4 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 MAR PY 2005 VL 149 IS 3 BP 444 EP 450 DI 10.1016/j.ahj.2004.06.033 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 917RV UT WOS:000228487800011 PM 15864232 ER PT J AU Rebeiz, AG Johanson, P Green, CL Crater, SW Roe, MT Langer, A Giugliano, RP Lincoff, AM Newby, LK Harrington, RA Topol, EJ Califf, RM Wagner, GS Krucoff, MW AF Rebeiz, AG Johanson, P Green, CL Crater, SW Roe, MT Langer, A Giugliano, RP Lincoff, AM Newby, LK Harrington, RA Topol, EJ Califf, RM Wagner, GS Krucoff, MW TI Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical trials) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY PATENCY; SUCCESSFUL REPERFUSION; PREDICTION; STANDARD; MARKERS AB We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with greater than or equal to50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutoneous coronary intervention can be performed. (C)2005 by Excerpta Medica Inc. C1 Duke Clin Res Inst, Durham, NC 27715 USA. Canadian Heart Res Ctr, Toronto, ON, Canada. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Rebeiz, AG (reprint author), Duke Clin Res Inst, 508 Fulton St,Room A3006, Durham, NC 27715 USA. EM kruco001@mc.duke.edu OI Topol, Eric/0000-0002-1478-4729 NR 12 TC 14 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2005 VL 95 IS 5 BP 611 EP 614 DI 10.1016/j.amjcard.2004.10.038 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 899PH UT WOS:000227156400012 PM 15721101 ER PT J AU Sun, BC Emond, JA Camargo, CA AF Sun, BC Emond, JA Camargo, CA TI Direct medical costs of syncope-related hospitalizations in the United States SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK STRATIFICATION; EMERGENCY AB Little is known about the costs of syncope-related admissions in the United States. A nationally representative sample of hospital discharges and reported charges was analyzed, and costs were estimated using Medicare cost-to-charge ratios. A conservative estimate of total annual costs for syncope-related hospitalizations was $2.4 billion (95% confidence interval [CI] $2.2 to $2.6 billion), with a mean cost of $5,400 (95% CI $5,100 to $5,600) per hospitalization. Efforts to safely decrease syncope-related admissions may result in substantial costs savings. (C) 2005 by Excerpta Medica Inc. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Sun, BC (reprint author), Robert Wood Johnson Clin Scholars Program, 911 Broxton Plaza,3rd Floor, Los Angeles, CA 90024 USA. NR 20 TC 128 Z9 132 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2005 VL 95 IS 5 BP 668 EP 671 DI 10.1016/j.amjcard.2004.11.013 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 899PH UT WOS:000227156400029 PM 15721118 ER PT J AU Terry, KL De Vivo, I Titus-Ernstoff, L Sluss, PM Cramer, DW AF Terry, KL De Vivo, I Titus-Ernstoff, L Sluss, PM Cramer, DW TI Genetic variation in the progesterone receptor gene and ovarian cancer risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE haplotypes; ovarian neoplasms; polymorphism; single nucleotide; receptors; progesterone ID FRAGMENT-LENGTH-POLYMORPHISM; CARCINOMA CELL-LINES; ORAL-CONTRACEPTIVES; NO ASSOCIATION; MIFEPRISTONE; APOPTOSIS; WOMEN; POPULATION; INSERTION; ESTROGEN AB Evidence suggests a role for progesterone in ovarian cancer development. Progesterone exerts its effect on target cells by interacting with its receptor. Thus, genetic variations that may cause alterations in the biologic functions of the progesterone receptor can potentially contribute to individual susceptibility to ovarian cancer. Using a population-based, case-control study, the authors genotyped four polymorphisms in the progesterone receptor gene (+44C/T, +331G/A, G393G, V660L) and inferred haplotypes in 987 ovarian cancer cases and 1,034 controls living in New Hampshire and eastern Massachusetts (May 1992-November 2002). Odds ratios and 95% confidence intervals were calculated to evaluate associations with ovarian cancer. No associations were observed between the +44C/T, +331G/A, and G393G polymorphisms and ovarian cancer. However, an inverse association was observed between the V660L variant and ovarian cancer (odds ratio = 0.70, 95% confidence interval: 0.57, 0.85). Associations remained after adjustment for potential confounders. Five haplotypes occurred with greater than 5% frequency, and the haplotype carrying the V660L variant had a significant association with ovarian cancer (odds ratio = 0.76, 95% confidence interval: 0.62, 0.92). Associations were similar after stratifying by ovarian cancer histologies and risk factors. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Norris Cotton Canc Ctr, Lebanon, NH USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Lebanon, NH USA. Dartmouth Coll Sch Med, Dept Med, Lebanon, NH USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Terry, KL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM kterry@hsph.harvard.edu FU NCI NIH HHS [CA10607-01, CA54419-10, R01 CA054419, R03 CA106079] NR 36 TC 45 Z9 46 U1 0 U2 0 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 MAR 1 PY 2005 VL 161 IS 5 BP 442 EP 451 DI 10.1093/aje/kwi064 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 899DX UT WOS:000227126200005 PM 15718480 ER PT J AU Kilbourne, AM Reynolds, CF Good, CB Sereika, SM Justice, AC Fine, MJ AF Kilbourne, AM Reynolds, CF Good, CB Sereika, SM Justice, AC Fine, MJ TI How does depression influence diabetes medication adherence in older patients? SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 01-04, 2003 CL HONOLULU, HI SP Amer Assoc Geriatr Psychiat ID ANTIHYPERTENSIVE MEDICATIONS; PHARMACY RECORDS; ALCOHOL-CONSUMPTION; REPORTED ADHERENCE; THERAPY; NONCOMPLIANCE; VALIDATION; IMPACT; CARE; PREVALENCE AB Objective: Using various measures (electronic monitoring, patient/provider report, pharmacy data), the authors assessed the association between depression and diabetes medication adherence among older patients with Type 2 diabetes. Methods: Patients completed a baseline survey on depression ( Patient Health Questionnaire) and were given electronic monitoring caps (EMCs) to use with their oral hypoglycemic medication. At the time of the patient baseline survey, providers completed a survey on their patients' overall medication adherence. Upon returning the caps after 30 days, patients completed a survey on their overall medication adherence. EMC adherence was defined as percent of days out of 30 with correct number of doses. Using pharmacy refill data from the patient baseline through 1 year later, they defined adherence as the percentage of days with adequate medication, based on days' supply across refill periods. Results: Of 203 patients ( mean age: 67 years), 10% ( N = 19) were depressed. Depressed patients were less likely to self-report good adherence and had a lower median percentage of days with adequate medication coverage ( on the basis of pharmacy refill data). After adjustment for alcohol use, cognitive impairment, age, and other medication use, depression was still negatively associated with adequate adherence, according to patient report and pharmacy data. Depression showed no associated with adherence on the basis of provider or EMC data. Conclusions: Depression was independently associated with inadequate medication adherence on the basis of patient self-report and pharmacy data. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Neurosci, Pittsburgh, PA USA. Intervent Res Ctr Study Late Life Mood Disorders, Pittsburgh, PA USA. Univ Pittsburgh, Sch Nursing, Ctr Res Chron Disorders, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. W Haven VA Med Ctr, West Haven, CT USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr C, Pittsburgh, PA 15240 USA. EM Amy.Kilbourne@med.va.gov NR 42 TC 26 Z9 26 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2005 VL 13 IS 3 BP 202 EP 210 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 900JH UT WOS:000227210700005 PM 15728751 ER PT J AU Kilbourne, AM Cornelius, JR Han, XY Haas, GL Salloum, I Conigliaro, J Pincus, HA AF Kilbourne, AM Cornelius, JR Han, XY Haas, GL Salloum, I Conigliaro, J Pincus, HA TI General-medical conditions in older patients with serious mental illness SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID BIPOLAR DISORDER; SCHIZOPHRENIA; COMORBIDITY; COSTS AB Objective: The burden of medical comorbidities was compared between older (greater than or equal to 60 years) and younger patients with serious mental illness. Methods: Patients (N = 8,083) diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder in 2001 were identified from VA facilities in the mid-Atlantic region. Medical comorbidities were identified by an ICD-9 based clinical classification algorithm. Results: Older, versus younger, patients were more likely to be diagnosed with cardiovascular or pulmonary conditions, and less likely to be diagnosed with substance-use disorders or hepatic conditions. Conclusions: More aggressive detection and management of general-medical comorbidities in older patients with serious mental illness is paramount. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot 151C, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RAND Corp, Pittsburgh, PA USA. Univ Pittsburgh, Hlth Inst, Pittsburgh, PA USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot 151C, Univ Dr C, Pittsburgh, PA 15240 USA. EM Amy.Kilbourne@med.va.gov NR 10 TC 55 Z9 55 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2005 VL 13 IS 3 BP 250 EP 254 DI 10.1176/appi.ajgp.13.3.250 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 900JH UT WOS:000227210700011 PM 15728757 ER PT J AU Barbeau, EM Goldman, R Roelofs, C Gagne, J Harden, E Conlan, K Stoddard, A Sorensen, G AF Barbeau, EM Goldman, R Roelofs, C Gagne, J Harden, E Conlan, K Stoddard, A Sorensen, G TI A new channel for health promotion: Building trade unions SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE prevention research; intervention design; qualitative survey; labor union; smoking control; diet; behavior change; cancer prevention; health disparities ID QUALITATIVE RESEARCH; VEGETABLE INTAKE; DISPARITIES; SMOKING; WORKING; WORKERS; TOBACCO; GENDER; FRUIT AB Purpose. Labor unions are a largely unevaluated channel for health promotion interventions for working class populations, who are at increased risk for smoking and poor diet. We conducted qualitative and quantitative research to understand the meaning and function Of union membership in workers' lives and applied this information to health promotion intervention design. Methods. Cross-sectional data included a survey conducted with a nationally representative sample of unionized construction workers (n = 1109; 44% response rate), and 16 focus groups (n = 88) conducted in multiple regions around the country. Results. The vast majority of survey respondents held strongly positive views of their union. Focus group findings revealed the meaning of the union in members' daily lives, how members view information from the union, and their perceptions of the union's limitations. Conclusions. The findings provide a compelling rationale for considering unions as a channel for health promotion interventions. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Brown Univ, Mem Hosp Rhode Isl, Brown Med Sch, Dept Family Med, Pawtucket, RI 02860 USA. Laborers Hlth & Safety Fund N Amer, Washington, DC USA. New England Res Inst, Watertown, MA 02172 USA. RP Barbeau, EM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,SM268, Boston, MA 02115 USA. EM Elizabeth_Barbeau@dfci.harvard.edu FU NCI NIH HHS [5 R01 CA84387-04] NR 25 TC 17 Z9 17 U1 0 U2 1 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAR-APR PY 2005 VL 19 IS 4 BP 297 EP 303 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 903TY UT WOS:000227449700005 PM 15768924 ER PT J AU Dave, S Honney, S Raymond, J Flume, PA AF Dave, S Honney, S Raymond, J Flume, PA TI An unusual presentation of cystic fibrosis in an adult SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE cystic fibrosis (CF); adult; metabolic alkalosis; diagnosis; hypokalemia ID METABOLIC ALKALOSIS; CHLORIDE DEFICIENCY; DIAGNOSIS; COMPLICATION; MUTATIONS; DISEASE AB The diagnosis of cystic fibrosis (CF) generally is made within the first few years of life, although some cases will not be diagnosed until adulthood. For most patients the diagnosis is suggested by typical CF-related symptoms such as chronic respiratory infection or maldigestion. The authors describe an adult patient with newly diagnosed CF whose presenting abnormalities consisted of hypokalemia and metabolic alkalosis. These are known complications of CF but are not common presenting features that lead to the diagnosis of CF. The authors discuss their patient's presentation and review his metabolic manifestations of CF. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Pediat, Charleston, SC 29425 USA. RP Dave, S (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, 96 Jonathan Lucas St,812-CSB, Charleston, SC 29425 USA. EM dave@musc.edu NR 21 TC 9 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2005 VL 45 IS 3 BP E41 EP E44 DI 10.1053/j.ajkd2004.11.009 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 909PT UT WOS:000227873000023 PM 15754262 ER PT J AU Linder, JA Huang, ES Steinman, MA Gonzales, R Stafford, RS AF Linder, JA Huang, ES Steinman, MA Gonzales, R Stafford, RS TI Fluoroquinolone prescribing in the United States: 1995 to 2002 SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE fluoroquinolones; antibiotics; physicians' practice patterns ID COMMUNITY-ACQUIRED PNEUMONIA; UNCOMPLICATED ACUTE BRONCHITIS; GROUP-A STREPTOCOCCI; ACUTE OTITIS-MEDIA; ANTIBIOTIC USE; ERYTHROMYCIN RESISTANCE; ANTIMICROBIAL THERAPY; ESCHERICHIA-COLI; ADULTS; GUIDELINES AB PURPOSE: To measure changes in the rate and type of fluoroquinolones prescribed in the United States from 1995 to 2002. METHODS: We performed a longitudinal analysis of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey of adult visits to physicians in ambulatory clinics and emergency departments throughout the United States from 1995 to 2002. The main outcomes were fluoroquinolone prescribing rates and prescribing in accordance with Food and Drug Administration approval as of December 2002. RESULTS: Between 1995 and 2002, fluoroquinolones became the most commonly prescribed class of antibiotics to adults in the United States. Fluoroquinolone prescribing rose threefold, from 7 million visits in 1995 to 22 million visits in 2002 (P < 0.0001). Fluoroquinolone prescribing increased as a proportion of overall antibiotic prescribing (from 10% to 24%; P < 0.0001) and as a proportion of the U.S. population (from 39 to 106 prescriptions per 1000 adults; P < 0.001). These increases were due to the use of newer fluoroquinolones with activity against Streptococcus pneumoniae. Forty-two percent of fluoroquinolone prescriptions were for nonapproved diagnoses. Among patients receiving antibiotics, nonapproved fluoroquinolone prescribing increased over time (odds ratio = 1.18 per year; 95% confidence interval: 1.13 to 1.24). CONCLUSION: Fluoroquinolone prescribing increased threefold in outpatient clinics and emergency departments in the United States from 1995 to 2002. Fluoroquinolones became the most commonly prescribed class of antibiotics to adults in 2002. Nonapproved fluoroquinolone prescribing was common and increased over time. Such prescribing patterns are likely to be followed by an increasing prevalence of fluoroquinolone-resistant bacteria. (c) 2005 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. Stanford Prevent Res Ctr, Program Prevent Outcomes & Practices, Stanford, CA USA. RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med, 1620 Tremont St,BC-3-2X, Boston, MA USA. FU AHRQ HHS [K08 HS014563, R01 HS11313]; BHP HRSA HHS [5T32PE11001-12]; NIA NIH HHS [K23 AG021963] NR 51 TC 153 Z9 156 U1 1 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2005 VL 118 IS 3 BP 259 EP 268 DI 10.1016/j.amjmed.2004.09.015 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 906PJ UT WOS:000227653900012 PM 15745724 ER PT J AU Houston, TK Allison, JJ Person, S Kovac, S Williams, OD Kiefe, CI AF Houston, TK Allison, JJ Person, S Kovac, S Williams, OD Kiefe, CI TI Post-myocardial infarction smoking cessation counseling: Associations with immediate and late mortality in older Medicare patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE myocardial infarctions; tobacco cessation; directive counseling; inpatients; mortality ID ACUTE MYOCARDIAL-INFARCTION; COOPERATIVE CARDIOVASCULAR PROJECT; CORONARY-ARTERY DISEASE; HEART-DISEASE; HOSPITALIZED-PATIENTS; QUALITY IMPROVEMENT; RANDOMIZED TRIAL; SUDDEN-DEATH; APACHE-II; CARE UNIT AB PURPOSE: To assess the difference in immediate (30 and 60 days after admission) and late (2-year) mortality between those who received inpatient post-myocardial infarction smoking cessation counseling and those who did not receive counseling METHODS: We conducted an observational study of a national random sample of inpatients front 2971 U.S. acute care hospitals participating in the Cooperative Cardiovascular Project in 1994-95. Medicare beneficiaries who were Current smokers over age 65, admitted with a documented acute myocardial infarction, and who were discharged to home were included (n = 16 743). Our main outcome measures were early (30-, 60-day) and late (1-, 2-year) mortality. RESULTS: Smoking cessation counseling was documented during their index hospitalization for 41 % of patients. Compared with those not counseled, those who received inpatient counseling had lower 30-day (2.0% vs. 3.0%), 60-day (3.7% vs. 5.6%), and 2-year mortality (25.0% vs. 30%) (logrank P < 0.0001). After adjustment for demographic characteristics, comorbid conditions, APACHE score, and receipt of treatments including aspirin, reperfusion, beta-blockers, and angiotensin-converting enzyme inhibitors, those receiving counseling were less likely to die within I year, but the effect was lost between I and 2 years [hazard ratio (HR) = 0.99 (0.91- 1.10)]. The greatest reduction in relative hazard (19%) was seen within 30 days [HR = 0.81 (95% confidence interval 0.65-0.99)]. CONCLUSION: Immediate and long-term mortality rates were lower among those receiving inpatient smoking cessation Counseling. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL 35294 USA. RP Houston, TK (reprint author), Univ Alabama, Dept Med, Div Prevent Med, 1530 3rd Ave S,FOT 720B, Birmingham, AL 35294 USA. EM tkhouston@uabmc.edu RI Houston, Thomas/F-2469-2013; OI Allison, Jeroan/0000-0003-4472-2112 NR 44 TC 37 Z9 37 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2005 VL 118 IS 3 BP 269 EP 275 DI 10.1016/j.amjmed.2004.12.007 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 906PJ UT WOS:000227653900013 PM 15745725 ER PT J AU Watensky, RP Weinstein, MC Kimmel, AD Seage, GR Losina, E Sax, PE Zhang, H Smith, HE Freedberg, KA Paltiel, AD AF Watensky, RP Weinstein, MC Kimmel, AD Seage, GR Losina, E Sax, PE Zhang, H Smith, HE Freedberg, KA Paltiel, AD TI Routine human immunodeficiency virus testing: An economic evaluation of current guidelines SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE HIV/AIDS; HIV EIA; testing; cost-effectiveness ID COMBINATION ANTIRETROVIRAL THERAPY; PRIMARY HIV-1 INFECTION; COST-EFFECTIVENESS; EMERGENCY-DEPARTMENT; UNITED-STATES; SEROPREVALENCE RATES; CONTROLLED-TRIAL; PLUS INDINAVIR; CELL COUNTS; CARE AB BACKGROUND: The Centers for Disease Control and Prevention guidelines recommend human immunodeficiency virus (HIV) counseling, testing, and referral for all patients in hospitals with an HIV prevalence of >= 1%. The 1% screening threshold has not been critically examined since HIV became effectively treatable in 1995. Our objective was to evaluate the clinical effect and cost-effectiveness of current guidelines and of alternate HIV prevalence thresholds. METHODS: We performed a cost-effectiveness analysis using a computer simulation model of HIV screening and disease as applied to inpatients in U.S. hospitals. RESULTS: At an undiagnosed inpatient HIV prevalence of 1% and an overall participation rate of 33%, HIV screening increased mean quality-adjusted life expectancy by 6.13 years per 1000 inpatients, with a cost-effectiveness ratio of $35 400 per quality-adjusted life-year (QALY) gained. Expansion of screening to settings with a prevalence as low as 0.1% increased the ratio to $64 500 per QALY gained. Increasing counseling and testing costs from $53 to $103 per person still yielded a cost-effectiveness ratio below $100 000 per QALY gained at a prevalence of undiagnosed infection of 0.1%. CONCLUSION: Routine inpatient HIV screening programs are not only cost-effective but would likely remain so at a prevalence of undiagnosed HIV infection 10 times lower than recommended thresholds. The current HIV counseling, testing, and referral guidelines should now be implemented nationwide as a way of linking infected patients to life-sustaining care. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. RP Watensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. OI Walensky, Rochelle P./0000-0002-8795-379X NR 68 TC 0 Z9 0 U1 3 U2 5 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 MAR PY 2005 VL 118 IS 3 BP 292 EP 300 DI 10.1016/j.amjmed.2004.07.055 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 906PJ UT WOS:000227653900016 ER PT J AU Voskas, D Jones, N Van Slyke, P Sturk, C Chang, W Haninec, A Babichev, YY Tran, J Master, Z Chen, S Ward, N Cruz, M Jones, J Kerbel, RS Jothy, S Dagnino, L Arbiser, J Klement, G Dumont, DJ AF Voskas, D Jones, N Van Slyke, P Sturk, C Chang, W Haninec, A Babichev, YY Tran, J Master, Z Chen, S Ward, N Cruz, M Jones, J Kerbel, RS Jothy, S Dagnino, L Arbiser, J Klement, G Dumont, DJ TI A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; HEMATOPOIETIC STEM-CELLS; OVEREXPRESSING ANGIOPOIETIN-1; DIFFERENTIAL EXPRESSION; PRECURSOR CELLS; BLOOD-VESSELS; UP-REGULATION; TUMOR-GROWTH; T-CELLS AB Psoriasis is a common, persistent skin disorder characterized by recurrent erythematous lesions thought to arise as a result of inflammatory cell infiltration and activation of keratinocyte proliferation. Unscheduled angiogenic growth has also been proposed to mediate the pathogenesis of psoriasis although the cellular and molecular basis for this response remains unclear. Recently, a role for the angiopoietin signaling system in psoriasis has been suggested by studies that demonstrate an up-regulation of the tyrosine kinase receptor Tie2 (also known as Tek) as well as angiopoietin-1 and angiopoietin-2 in human psoriatic lesions. To examine temporal expression of Tie2, we have developed a binary transgenic approach whereby expression of Tie2 can be conditionally regulated by the presence of tetracycline analogs in double-transgenic mice. A psoriasis-like phenotype developed in double-transgenic animals within 5 days of birth and persisted throughout adulthood. The skin of affected mice exhibited many cardinal features of human psoriasis including epidermal hyperplasia, inflammatory cell accumulation, and altered dermal angiogenesis. These skin abnormalities resolved completely with tetracycline-mediated suppression of transgene expression, thereby illustrating a complete dependence on Tie2 signaling for disease maintenance and progression. Furthermore, the skin lesions in double-transgenic mice markedly improved after administration of the immunosuppressive anti-psoriatic agent cyclosporine, thus demonstrating the clinical significance of this new model. C1 Sunnybrook & Womens Res Inst, Div Mol & Cellular Biol, Toronto, ON M4N 3M5, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Case Western Reserve Univ, Dept Anat, Cleveland, OH 44106 USA. St Michaels Hosp, Dept Lab Med & Pathol, Toronto, ON M5B 1W8, Canada. Univ Western Ontario, Dept Physiol, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Pharmacol & Paediat, London, ON N6A 3K7, Canada. Child Hlth Res Inst, London, ON, Canada. Lawson Hlth Res Inst, London, ON, Canada. Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Dumont, DJ (reprint author), Sunnybrook & Womens Res Inst, Div Mol & Cellular Biol, 2075 Bayview Ave,Res Bldg,S-227, Toronto, ON M4N 3M5, Canada. EM dan.dumont@swri.ca OI Ward, Nicole L./0000-0003-1907-2621 FU NHLBI NIH HHS [R01 HL063224, HL63224-01] NR 57 TC 48 Z9 50 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 2005 VL 166 IS 3 BP 843 EP 855 DI 10.1016/S0002-9440(10)62305-X PG 13 WC Pathology SC Pathology GA 901ND UT WOS:000227288300021 PM 15743796 ER PT J AU Schacht, V Dadras, SS Johnson, LA Jackson, DG Hong, YK Detmar, M AF Schacht, V Dadras, SS Johnson, LA Jackson, DG Hong, YK Detmar, M TI Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-C; METASTATIC SPREAD; CUTANEOUS MELANOMA; I CELLS; LYMPHANGIOGENESIS; PROMOTES; CLONING; INDUCTION; ANTIGEN; LYVE-1 AB The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning. However, research into the biological importance of podoplanin has been hampered by the lack of a generally available antibody against the human protein, and its expression in normal-tissues and in human malignancies has remained unclear. We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses. We found that, in addition to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal reticular cells and follicular dendritic cells of lymphoid organs. These findings were confirmed in normal mouse tissues with anti-podoplanin antibody 8.1.1. Podoplanin was also strongly expressed by granulosa cells in normal ovarian follicles, and by ovarian dysgerminomas and granulosa cell tumors. Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied. These findings suggest a potential role of podo-planin in tumor progression, and they also identify the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers. C1 Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Charlestown, MA USA. John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. RP Detmar, M (reprint author), Swiss Fed Inst Technol, Inst Pharmaceut Sci, Wolfgang Pauli Str 10,HCI H303, CH-8093 Zurich, Switzerland. EM michael.detmar@pharma.ethz.ch FU NCI NIH HHS [5T32CA09216, CA69184, CA86410, CA92644, P01 CA092644, R01 CA069184, R01 CA086410, T32 CA009216] NR 36 TC 402 Z9 433 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 2005 VL 166 IS 3 BP 913 EP 921 DI 10.1016/S0002-9440(10)62311-5 PG 9 WC Pathology SC Pathology GA 901ND UT WOS:000227288300027 PM 15743802 ER PT J AU Gallagher, RM AF Gallagher, RM TI Rational integration of pharmacologic behavioral and rehabilitation strategies in the treatment of chronic pain SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Review DE biopsychosocial; chronicity; chronic pain; pain conditions; pain management; pain medicine; persistent pain; rational polypharmacy; treatment planning ID LOW-BACK-PAIN; FUNCTIONAL RESTORATION; FOLLOW-UP; COGNITIVE INTERVENTION; PSYCHOLOGICAL-FACTORS; WORKERS COMPENSATION; OPIOID THERAPY; LUMBAR FUSION; PRIMARY-CARE; MANAGEMENT AB Historically, the concept of a mind-body duality in medicine, which supports a biomedical approach to pain management, has impeded the development of adequate treatments for persistent pain conditions and diseases. Although usually there is an initiating pathophysiologic nociceptive cause of pain, over time, the conditioning of neurophysiologic and affective systems by environmental and internal events can promote chronicity and frustrate the efforts of physicians to attenuate nociceptive processes. A full elucidation of the environmental and psychological factors contributing to pain and suffering may prove difficult using a traditional biomedical approach. Prevention of chronicity, by early identification and treatment of pain generators and the pain response to tissue injury and by recognition of those general factors that contribute to risk for chronicity (e.g., depressive illness, poor pain control), is crucial for any healthcare system that wishes to reduce the morbidity and costs of persistent pain. Goal-directed, outcomes-focused biopsychosocial treatment plans that efficiently integrate physical, behavioral, and medical approaches more frequently achieve better pain control and improved function. The following article presents a general overview of evidence for effectiveness of these approaches and some central principles of integrated treatment planning. C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia Vet Affairs Off,Pain Management Serv, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia Vet Affairs Off,Pain Management Serv, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 84 TC 10 Z9 10 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAR PY 2005 VL 84 IS 3 SU S BP S64 EP S76 DI 10.1097/01.PHM.0000154910.01200.0B PG 13 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 900KQ UT WOS:000227214200007 PM 15722785 ER PT J AU Gallagher, RM AF Gallagher, RM TI Pain science and rational polypharmacy - An historical perspective SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Editorial Material DE chronic pain; pharmacology; history C1 Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAR PY 2005 VL 84 IS 3 SU S BP S1 EP S3 DI 10.1097/01.PHM.0000154909.96213.60 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 900KQ UT WOS:000227214200001 PM 15722779 ER PT J AU Cohen, DM AF Cohen, DM TI SRC family kinases in cell volume regulation SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Review DE hypotonicity; transient receptor potential; hypertonicity; ion transport; tyrosine kinase ID EPIDERMAL-GROWTH-FACTOR; K-CL COTRANSPORTER; ACTIVATED PROTEIN-KINASE; OSMOTIC RESPONSE ELEMENT; RECEPTOR TYROSINE KINASES; GATED POTASSIUM CHANNEL; COLLECTING DUCT CELLS; MICE LACKING TRPV4; FACTOR HB-EGF; SIGNAL-TRANSDUCTION AB SRC family kinases are a group of nine cytoplasmic protein tyrosine kinases essential for many cell functions. Some appear to be ubiquitously expressed, whereas others are highly tissue specific. The ability of members of the SRC family to influence ion transport has been recognized for several years. Mounting evidence suggests a broad role for SRC family kinases in the cell response to both hypertonic and hypotonic stress, and in the ensuing regulatory volume increase or decrease. In addition, members of this tyrosine kinase family participate in the mechanotransduction that accompanies cell membrane deformation. Finally, at least one SRC family member operates in concert with the p38 MAPK to regulate tonicity-dependent gene transcription. C1 Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Div Nephrol, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM cohend@ohsu.edu NR 159 TC 54 Z9 57 U1 0 U2 0 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 MAR PY 2005 VL 288 IS 3 BP C483 EP C493 DI 10.1152/ajpcell.00452.2004 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 894ME UT WOS:000226795100001 PM 15692147 ER PT J AU Sugita, H Kaneki, M Sugita, M Yasukawa, T Yasuhara, S Martyn, JAJ AF Sugita, H Kaneki, M Sugita, M Yasukawa, T Yasuhara, S Martyn, JAJ TI Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article ID FOXO TRANSCRIPTION FACTORS; AKT KINASE-ACTIVITY; OBESE ZUCKER RATS; UBIQUITIN LIGASES; PROTEIN-SYNTHESIS; GENE-EXPRESSION; MYOTUBE HYPERTROPHY; SIGNAL-TRANSDUCTION; GLUCOSE-TRANSPORT; THERMAL-INJURY AB The molecular bases underlying burn- or critical illness-induced insulin resistance still remain unclarified. Muscle protein catabolism is a ubiquitous feature of critical illness. Akt/PKB plays a central role in the metabolic actions of insulin and is a pivotal regulator of hypertrophy and atrophy of skeletal muscle. We therefore examined the effects of burn injury on insulin-stimulated Akt/PKB activation in skeletal muscle. Insulin-stimulated phosphorylation of Akt/PKB was significantly attenuated in burned compared with sham-burned rats. Insulin-stimulated Akt/PKB kinase activity, as judged by immune complex kinase assay and phosphorylation status of the endogenous substrate of Akt/PKB, glycogen synthase kinase-3beta (GSK-3beta), was significantly impaired in burned rats. Furthermore, insulin consistently failed to increase the phosphorylation of p70 S6 kinase, another downstream effector of Akt/PKB, in rats with burn injury, whereas phosphorylation of p70 S6 kinase was increased by insulin in controls. The protein expression of Akt/PKB, GSK-3beta, and p70 S6 kinase was unaltered by burn injury. However, insulin-stimulated activation of ERK, a signaling pathway parallel to Akt/PKB, was not affected by burn injury. These results demonstrate that burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle and suggest that attenuated Akt/PKB activation may be involved in deranged metabolism and muscle wasting observed after burn injury. C1 Shriners Hosp Children, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Martyn, JAJ (reprint author), 55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01-DK-058127]; NIGMS NIH HHS [R01-GM-055082, R01 GM055082, R01-GM-61411, GM-21700, R01-GM-31569] NR 57 TC 56 Z9 60 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 MAR PY 2005 VL 288 IS 3 BP E585 EP E591 DI 10.1152/ajpendo.00321.2004 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 894MD UT WOS:000226795000015 PM 15536206 ER PT J AU Furukawa, O Hirokawa, M Zhang, LN Takeuchi, T Bi, LC Guth, PH Engel, E Akiba, Y Kaunitz, JD AF Furukawa, O Hirokawa, M Zhang, LN Takeuchi, T Bi, LC Guth, PH Engel, E Akiba, Y Kaunitz, JD TI Mechanism of augmented duodenal HCO3- secretion after elevation of luminal CO2 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE bicarbonate; duodenum; carbon dioxide; carbonic anhydrase; cyclooxygenase; epithelial cells; sodium hydrogen exchanger 1; sodium hydrogen exchanger 3; sodium bicarbonate cotransporter 1 ID MUCOSAL ALKALINE SECRETION; APICAL CL-/HCO3-EXCHANGER; BICARBONATE SECRETION; CARBONIC-ANHYDRASE; CYSTIC-FIBROSIS; GASTROINTESTINAL-TRACT; RAT; ACID; CFTR; TRANSPORT AB The proximal duodenum is exposed to extreme elevations of PCO2 because of the continuous mixture of secreted HCO3- with gastric acid. These elevations (up to 80 kPa) are likely to place the mucosal cells under severe acid stress. Furthermore, we hypothesized that, unlike most other cells, the principal source of CO2 for duodenal epithelial cells is from the lumen. We hence examined the effect of elevated luminal PCO2 on duodenal HCO3- secretion (DBS) in the rat. DBS was measured by the pH-stat method. For CO2 challenge, the duodenum was superfused with a high PCO2 solution. Intracellular pH (pH(i)) of duodenal epithelial cells was measured by ratio microfluorometry. CO2 challenge, but not isohydric solutions, strongly increased DBS to approximately two times basal for up to 1 h. Preperfusion of the membrane-permeant carbonic anhydrase inhibitor methazolamide, or continuous exposure with indomethacin, fully inhibited CO2-augmented DBS. Dimethyl amiloride (0.1 mM), an inhibitor of the basolateral sodium-hydrogen exchanger 1, also inhibited CO2-augumented DBS, although S-3226, a specific inhibitor of apical sodium-hydrogen exchanger 3, did not. DIDS, an inhibitor of basolateral sodium-HCO3- cotransporter, also inhibited CO2-augemented DBS, as did the anion channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid. CO2 decreased epithelial cell pHi, followed by an overshoot after removal of the CO2 solution. We conclude that luminal CO2 diffused in the duodenal epithelial cells and was converted to H+ and HCO3- by carbonic anhydrase. H+ initially exited the cell, followed by secretion of HCO3-. Secretion was dependent on a functioning basolateral sodium/proton exchanger, a functioning basolateral HCO3- uptake mechanism, and submucosal prostaglandin generation and facilitated hydration of CO2 into HCO3- and H+. C1 Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA USA. Univ Calif Irvine, Dept Med, Div Gastroenterol, Irvine, CA 92717 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Rm 217,Bldg 114, Los Angeles, CA 90073 USA. EM jake@ucla.edu NR 46 TC 23 Z9 25 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2005 VL 288 IS 3 BP G557 EP G563 DI 10.1152/ajpgi.00344.2004 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 895AM UT WOS:000226833100020 PM 15499081 ER PT J AU Xu, Y Gen, M Lu, L Fox, J Weiss, SO Brown, RD Perlov, D Ahmad, H Zhu, PL Greyson, C Long, CS Schwartz, GG AF Xu, Y Gen, M Lu, L Fox, J Weiss, SO Brown, RD Perlov, D Ahmad, H Zhu, PL Greyson, C Long, CS Schwartz, GG TI PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nuclear receptor; thiazolidinedione; energy metabolism; cytokine; ventricular function ID NECROSIS-FACTOR-ALPHA; RECEPTOR-GAMMA; ISCHEMIA/REPERFUSION INJURY; PEROXISOME PROLIFERATION; MITOCHONDRIAL-FUNCTION; ANTIDIABETIC AGENT; SKELETAL-MUSCLE; GENE-EXPRESSION; INFARCT SIZE; YOUNG-PIGS AB PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs. Am J Physiol Heart Circ Physiol 288: H1314-H1323, 2005. First published November 4, 2004; doi:10.1152/ajpheart. 00618.2004.-Peroxisome proliferator-activated receptor (PPAR)-gamma modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-gamma activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-gamma activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both alpha-tocopherol and thiazolidinedione moieties, whether PPAR-gamma activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone ( 75 mg(.)kg(-1) (.) day(-1)), rosiglitazone (3 mg (.) kg(-1 .) day(-1)), or alpha-tocopherol (73 mg (.) kg(-1) (.) day(-1), equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-gamma, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or alpha-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an alpha-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-gamma activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its alpha-tocopherol moiety. These findings, in conjunction with prior rat studies, suggest interspecies differences in the response to PPAR-gamma activation in the heart. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, Cardiol Sect, 111B,1055 Clermont St, Denver, CO 80220 USA. EM Gregory.Schwartz@med.va.gov FU NHLBI NIH HHS [R01 HL049944, R01 HL068606, R01 HL049944-09, HL-68606, HL-49944, R56 HL049944] NR 60 TC 32 Z9 34 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 MAR PY 2005 VL 288 IS 3 BP H1314 EP H1323 DI 10.1152/ajpheart.00618.2004 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 896CB UT WOS:000226911100044 PM 15528232 ER PT J AU Teran, FJ Johnson, RA Stevenson, BK Peyton, KJ Jackson, KE Appleton, SD Durante, W Johnson, FK AF Teran, FJ Johnson, RA Stevenson, BK Peyton, KJ Jackson, KE Appleton, SD Durante, W Johnson, FK TI Heme oxygenase-derived carbon monoxide promotes arteriolar endothelial dysfunction and contributes to salt-induced hypertension in Dahl salt-sensitive rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE salt-sensitive hypertension; vascular tone; arterioles; blood pressure ID NITRIC-OXIDE SYNTHASE; GRACILIS MUSCLE ARTERIOLES; ANGIOTENSIN-II; VENTRICULAR HYPERTROPHY; GUANYLYL CYCLASE; L-ARGININE; VASODILATION; INHIBITION; EXPRESSION; VASOCONSTRICTION AB Vascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). Heme-derived CO inhibits nitric oxide synthase and promotes endothelium-dependent vasoconstriction. After 4 wk of high-salt diet, Dahl salt-sensitive (Dahl-S) rats display hypertension, increased vascular HO-1 expression, and attenuated vasodilator responses to ACh that can be completely restored by acute treatment with an inhibitor of HO. In this study, we examined the temporal development of HO-mediated endothelial dysfunction in isolated pressurized first-order gracilis muscle arterioles, identified the HO product responsible, and studied the blood pressure effects of HO inhibition in Dahl-S rats on a high-salt diet. Male Dahl-S rats (5-6 wk) were placed on high-salt (8% NaCl) or low-salt (0.3% NaCl) diets for 0-4 wk. Blood pressure increased gradually, and responses to an endothelium-dependent vasodilator, ACh, decreased gradually with the length of high-salt diet. Flow-induced dilation was abolished in hypertensive Dahl-S rats. Acute in vitro pretreatment with an inhibitor of HO, chromium mesoporphyrin (CrMP), restored endothelium-dependent vasodilation and abolished the differences between groups. The HO product CO prevented the restoration of endothelium-dependent dilation by CrMP. Furthermore, administration of an HO inhibitor lowered blood pressure in Dahl-S rats with salt-induced hypertension but did not do so in low-salt control rats. These results suggest that hypertension and HO-mediated endothelial dysfunction develop gradually and simultaneously in Dahl-S rats on high-salt diets. They also suggest that HO-derived CO underlies the impaired endothelial dysfunction and contributes to hypertension in Dahl-S rats on high-salt diets. C1 Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA. Tulane Univ, Hlth Sci Ctr, Tulane Hyperten & Renal Ctr Excellence, New Orleans, LA 70112 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Johnson, FK (reprint author), Tulane Univ, Hlth Sci Ctr, Dept Physiol, 1430 Tulane Ave,SL39, New Orleans, LA 70112 USA. EM Fruzsi123@aol.com FU NCRR NIH HHS [P20 RR 017659]; NHLBI NIH HHS [R01 HL 64577, R01 HL 76187, R01 HL 59976] NR 46 TC 34 Z9 36 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 MAR PY 2005 VL 288 IS 3 BP R615 EP R622 DI 10.1152/ajpregu.00123.2004 PG 8 WC Physiology SC Physiology GA 895AJ UT WOS:000226832800010 PM 15528397 ER PT J AU Feliers, D Duraisamy, S Barnes, JL Ghosh-Choudhury, G Kasinath, BS AF Feliers, D Duraisamy, S Barnes, JL Ghosh-Choudhury, G Kasinath, BS TI Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE protein expression; polysomes; nephropathy ID MESSENGER-RNA; PROTEIN-SYNTHESIS; DIABETIC-NEPHROPATHY; SIGNALING PATHWAY; FACTOR-BETA; RETINAL NEOVASCULARIZATION; VEGF EXPRESSION; INITIATION; PHOSPHORYLATION; RECEPTOR AB Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II. Am J Physiol Renal Physiol 288: F521-F529, 2005. First published November 30, 2004; doi:10.1152/ ajprenal.00271.2004.-ANG II regulates growth factor expression in the kidney. We investigated whether ANG II regulated vascular endothelial growth factor (VEGF) synthesis in proximal tubular epithelial (MCT) cells. ANG II (1 nM) increased VEGF protein expression within 5 min, the effect lasting for 30 min. There was no change in VEGF mRNA levels or mRNA stability, and transcription inhibitors did not affect ANG II-induced VEGF expression. Regulation of VEGF translation was investigated. Polyribosomal analysis revealed selective enrichment of heavy ribosomes (polysomes) with VEGF mRNA transcripts compared with light ribosomes in ANG II-treated cells, although distribution of GAPDH was unaltered. In vitro translation of total RNA from polysomal fractions showed selective increase in VEGF protein synthesis in ANG II-treated cells. Preincubation with LY-294002, a PI 3-kinase inhibitor, or expression of dominant-negative Akt prevented ANG II-stimulated increase in VEGF translation. ANG 11 increased phosphorylation of eukaryouic initiation factor 4E and its binding protein 4E-BP1, critical events that regulate the initiation phase of protein translation. ANG 11 failed to increase VEGF mRNA translation in cells stably expressing the phosphorylation mutant of 4E-BP1. Our data illustrate that a rapid increase in VEGF protein expression by ANG 11 is regulated at the initiation phase of translation of VEGF mRNA in renal epithelial cells. Regulation of VEGF translation by ANG 11 represents a novel pathway of renal response to injury. C1 Univ Texas, Hlth Sci Ctr, Dept Med Nephrol, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU NIDDK NIH HHS [R01-DK-55815, R01-DK-50190] NR 52 TC 34 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2005 VL 288 IS 3 BP F521 EP F529 DI 10.1152/ajprenal.00271.2004 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 898IK UT WOS:000227070300012 PM 15572520 ER PT J AU Kern, RS Green, MF Mitchell, S Kopelowicz, A Mintz, J Liberman, RP AF Kern, RS Green, MF Mitchell, S Kopelowicz, A Mintz, J Liberman, RP TI Extensions of errorless learning for social problem-solving deficits in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 42nd Meeting of the American-College-of-Neuropsychopharmacology CY DEC 07-11, 2003 CL San Juan, PR SP Amer Coll Neuropsychopharmacol ID MEMORY; PERFORMANCE; REHABILITATION; INDIVIDUALS; IMPAIRMENT; DEMENTIA; SKILLS; TRIAL AB Objective: There is a clear need to develop psychosocial rehabilitation methods that compensate for neurocognitive deficits common to persons with severe and persistent mental illness. Errorless learning, a compensatory training intervention, has been successful in teaching entry-level job tasks. However, errorless learning's applicability to broader, more complex functions is unknown. The present study tested the extension of errorless learning for deficits in social problem-solving skills in patients with schizophrenia. Method: Sixty clinically stable outpatients with schizophrenia or schizoaffective disorder were stratified by gender and level of memory impairment before being randomly assigned to one of two training programs: errorless learning or symptom management. Groups were matched for training time, format and structure of training, and types of teaching aids used. Social problem-solving ability, measured by the Assessment of Interpersonal Problem-Solving Skills, was assessed at baseline, within 2 days of training completion, and after 3 months. Dependent measures were the scores for the receiving, processing, and sending skills areas from the Assessment of Interpersonal Problem-Solving Skills. Results: A repeated-measures analysis of covariance was conducted for each dependent measure with baseline Assessment of Interpersonal Problem-Solving Skills score entered as a covariate. For all three skills, there was a significant training group effect favoring errorless learning. Durability of errorless learning training effects extended to the 3-month follow-up assessment for processing and sending skills but not receiving skills. Conclusions: Results support the extension of errorless learning to complex functions such as social problem-solving skills in the rehabilitation of persons with schizophrenia. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. San Fernando Mental Hlth Ctr, Mission Hills, CA USA. Dept Vet Affairs VISN 22 Mental Illness Res Educ, Mission Hills, CA USA. RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Syst MIRECC 210, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rkern@ucla.edu OI kopelowicz, alex/0000-0002-1728-4105 NR 37 TC 50 Z9 54 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2005 VL 162 IS 3 BP 513 EP 519 DI 10.1176/appi.ajp.162.3.513 PG 7 WC Psychiatry SC Psychiatry GA 904UP UT WOS:000227523500014 PM 15741468 ER PT J AU Onitsuka, T Nestor, PG Gurrera, RJ Shenton, ME Kasai, K Frumin, M Niznikiewicz, MA McCarley, RW AF Onitsuka, T Nestor, PG Gurrera, RJ Shenton, ME Kasai, K Frumin, M Niznikiewicz, MA McCarley, RW TI Association between reduced extraversion and right posterior fusiform gyrus gray matter reduction in chronic schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID VOLUME REDUCTION; RECOGNITION AB Objective: The authors examined the association between volume of the fusiform gyrus, a region involved in face processing, and the personality trait of extraversion in patients with schizophrenia. Method: Male patients (N = 24) and age-matched male comparison subjects (N = 26) completed NEO Five-Factor Inventory personality measures of extraversion and underwent high-spatial-resolution magnetic resonance imaging of anterior and posterior fusiform gyrus gray matter. Results: Low extraversion scores were significantly correlated with gray matter volume reductions in the right posterior fusiform gyrus for patients but not comparison subjects. Conclusions: Reduced right posterior fusiform gyrus volume may contribute to disease-related social disturbances, characterized by both low extraversion and reduced sensitivity to human faces. C1 Harvard Med Sch, VA Boston Healthcare Syst, Brockton Div, Dept Psychiat,Lab Neurosci,Clin Neurosci Div, Boston, MA USA. Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, MRI Div, Boston, MA 02115 USA. RP Shenton, ME (reprint author), Harvard Med Sch, Boston VA Healthcare Syst, Brockton Div, Dept Psychiat 116A, 904 Belmont St, Brockton, MA 02301 USA. EM martha_shenton@hms.harvard.edu; robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [R01 MH-40799, K02 MH-01110, K02 MH001110, K02 MH001110-10, R01 MH-50747, R01 MH040799, R01 MH050740, R01 MH050740-07] NR 8 TC 21 Z9 21 U1 1 U2 2 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 MAR PY 2005 VL 162 IS 3 BP 599 EP 601 DI 10.1176/appi.ajp.162.3.599 PG 3 WC Psychiatry SC Psychiatry GA 904UP UT WOS:000227523500025 PM 15741479 ER PT J AU Pan, J Barbeau, EM Levenstein, C Balbach, ED AF Pan, J Barbeau, EM Levenstein, C Balbach, ED TI Smoke-free airlines and the role of organized labor: A case study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID TOBACCO INDUSTRY; UNIONS AB Labor unions play an important role in debates about smoke-free worksites. We investigated the role of flight attendants and their unions in creating smoke-free air travel. We used case study methodology to search tobacco industry documents and labor union periodicals and to interview key informants (i.e., people identified as having first-hand information and experience in the campaign to make airlines smoke free). We then compared findings across these data sources. Tobacco industry strategies against the establishment of smoke-free worksites failed in the case of airlines, largely because of the efforts of flight attendants and their unions. Other factors contributed to the failure but likely would have been insufficient to derail industry efforts without strong stands by the flight attendants. This case illustrates the potential for successful partnerships between unions and tobacco control policy advocates when developing smoke-free worksite policies. C1 Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Soc, Boston, MA USA. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. RP Pan, J (reprint author), Tufts Univ, Community Hlth Program, 112 Packard Ave, Medford, MA 02155 USA. EM jocelyn.pan@tufts.edu FU NCI NIH HHS [5R01 CA095964-03, R01 CA095964] NR 48 TC 13 Z9 13 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2005 VL 95 IS 3 BP 398 EP 404 DI 10.2105/AJPH.2004.040592 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 918AR UT WOS:000228511100016 PM 15727966 ER PT J AU Levy, MM Baylor, MS Bernard, GR Fowler, R Franks, TJ Hayden, FG Helfand, R Lapinsky, SE Martin, TR Niederman, MS Rubenfeld, GD Slutsky, AS Stewart, TE Styrt, BA Thompson, BT Harabin, AL AF Levy, MM Baylor, MS Bernard, GR Fowler, R Franks, TJ Hayden, FG Helfand, R Lapinsky, SE Martin, TR Niederman, MS Rubenfeld, GD Slutsky, AS Stewart, TE Styrt, BA Thompson, BT Harabin, AL TI Clinical issues and research in respiratory failure from severe acute respiratory syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; infectious disease ID CRITICALLY-ILL PATIENTS; MECHANICALLY VENTILATED PATIENTS; INTENSIVE-CARE UNIT; SARS-ASSOCIATED CORONAVIRUS; COMMUNITY-ACQUIRED PNEUMONIA; ACUTE LUNG INJURY; DISTRESS-SYNDROME; INTERFERON-ALPHA; GASTROESOPHAGEAL-REFLUX; VENOUS THROMBOEMBOLISM AB The National Heart, Lung, and Blood Institute, along with the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases, convened a panel to develop recommendations for treatment, prevention, and research for respiratory failure from severe acute respiratory syndrome (SARS) and other newly emerging infections. The clinical and pathological features of acute lung injury (ALI) from SARS appear indistinguishable from ALI from other causes. The mainstay of treatments for ALI remains supportive. Patients with ALI from SARS who require mechanical ventilation should receive a lung protective, low tidal volume strategy. Adjuvant treatments recommended include prevention of venous thromboembolism, stress ulcer prophylaxis, and semirecumbent positioning during ventilation. Based on previous experience in Canada, infection control resources and protocols were recommended. Leadership structure, communication, training, and morale are an essential aspect of SAIRS management. A multicenter, placebo-controlled trial of corticosteroids for late SARS is justified because of widespread clinical use and uncertainties about relative risks and benefits. Studies of combined pathophysiologic endpoints were recommended, with mortality as a secondary endpoint. The group recommended preparation for studies, including protocols, ethical considerations, Web-based registries, and data entry systems. C1 NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. Brown Univ, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Univ Virginia, Dept Internal Med, Charlottesville, VA USA. Ctr Dis Control & Prevent, Resp & Enter Viruses Branch, Atlanta, GA USA. VA Puget Sound Med Ctr, Div Pulm & Crit Care Med, Seattle, WA USA. Winthrop Univ Hosp, Dept Med, Mineola, NY 11501 USA. Univ Washington, Harborview Med Ctr, Dept Pulm & Crit Care Med, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Sunnybrook & Womens Coll Hlth Sci Ctr, Interdept Div Crit Care Med, Toronto, ON, Canada. Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. Mt Sinai Hosp, Dept Crit Care Med, Toronto, ON M5G 1X5, Canada. Univ Hlth Network, Toronto, ON, Canada. St Michaels Hosp, Dept Med, Toronto, ON M5B 1W8, Canada. St Michaels Hosp, Dept Crit Care, Toronto, ON M5B 1W8, Canada. RP Harabin, AL (reprint author), NHLBI, Div Lung Dis, NIH, 6,701 Rockledge Dr,Room 10018, Bethesda, MD 20892 USA. EM harabin@nih.gov RI Slutsky, Arthur/A-6013-2008; Lapinsky, Stephen/C-4624-2015 OI Slutsky, Arthur/0000-0002-6063-3876; Lapinsky, Stephen/0000-0002-6930-0306 NR 84 TC 25 Z9 26 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2005 VL 171 IS 5 BP 518 EP 526 DI 10.1164/rccm.200405-621WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 900EF UT WOS:000227197500016 PM 15591472 ER PT J AU Qin, M Escuadro, B Sharma, S Batra, RK AF Qin, M Escuadro, B Sharma, S Batra, RK TI Gene transfer mediated by native versus fibroblast growth factor-retargeted adenoviral vectors into lung cancer cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE CAR; FGF2; gene therapy; lungcancer; molecular conjugates ID FACTOR RECEPTORS; REDUCED TOXICITY; FGF RECEPTORS; DELIVERY; EXPRESSION; TROPISM; CARCINOMAS; EFFICIENCY; PATHWAYS; ANTIBODY AB We compared native Adenoviral (Ad) vectors to a basic Fibroblast Growth Factor-retargeted Adenovirus (FGF2-Ad) for gene delivery into a diverse panel of lung cancer cells in vitro and xenografts in vivo. Cells were first evaluated for vector-specific receptor expression. Marked variations of surface coxsackie-adenovirus receptor (CAR), but relatively similar levels of a v integrin and FGF receptor expression were evident. Transduction efficiency by Ad directly correlated (R = 0.77, 95% CI 0.28-0.94, P = 0.0085) with CAR, but not with a v integrin expression. Transduction efficiency by FGF2-Ad did not correlate with the measured FGF receptor expression. Blocking studies indicated that gene transfer by FGF2-Ad occurred by a CAR-independent pathway, and could be inhibited by free FGF in a dose-dependent manner. Ad-antiserum inhibited FGF2-Ad gene transfer, suggesting that the Ad-component was needed for post-entry DNA-delivery. Soluble heparin sulfate proteoglycans (HSPG) or a v integrin blockers marginally decreased FGF2-Ad transduction. Both Ad and FGF2-Ad equally transduced CAR-positive non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells. By contrast, FGF2-Ad had a distinct transduction advantage in CAR-deficient NSCLC cells. This improvement in transduction of CAR-deficient cells by FGF2-Ad persisted in vivo. These data justify the need for an improved FGF2-Ad vector for clinical use in CAR-deficient lung cancer. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rbatra@ucla.edu OI Batra, Raj K./0000-0002-1126-543X FU NCI NIH HHS [R01 CA078654-03, R01 CA 78654]; PHS HHS [1P50 90388] NR 36 TC 7 Z9 7 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 2005 VL 32 IS 3 BP 211 EP 217 DI 10.1165/rcmb.2004-0226OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 900DS UT WOS:000227196200006 PM 15626775 ER PT J AU Busaba, NY de Oliveira, LV Kieff, DL AF Busaba, NY de Oliveira, LV Kieff, DL TI Correlation between preoperative clinical diagnosis and histopathological findings in patients with rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the Triological-Society CY JAN 23-25, 2004 CL New York, NY SP Triol Soc ID NASAL POLYPS; PARANASAL SINUSES; SARCOIDOSIS; AMYLOIDOSIS; NOSE AB Background: P e diagnosis of chronic rhinosinusitis (CRS) or chronic rhinosinusitis with polyposis (CRSP) is typically, clinical and based on the combination of medical history, physical examination, and imaging. The recommendation to perform surgery; and the type of surgery; is tailored to the diagnosis. The objective of this study is to determine the accuracy of preoperative clinical CRS or CRSP diagnosis in patienis who underwent endoscopic sinus surgery. Methods: This is a retrospective review of a case series of 380 consecutive patients who underwent endoscopic sinus surgery for the preoperative clinical diagnosis of CRS or bilateral CRSP. Data regarding symptoms, nasal endoscopy, computed tomography findings, preoperative diagnosis, and postoperative histopathology results were collected. Results: The preoperative diagnoses were CRS (n = 180) and 0 CRSP (it = 206). Two of the 180 patients (1.1%) with the preoperative diagnosis of CRS had a different postoperative histopathological diagnosis. The histopathology in both patients showed noncaseating granulomata, leading to a diagnosis of sarcoidosis. Nine of the 200 patients (4.5%) with the preoperative diagnosis of CRSP had a different postoperative histopathological diagnosis. Of these nine patients, five had inverted papilloma (bilaterally in one instance); one had adenocarcinoma; one had squamous-cell carcinoma; one had chronic invasive granulomatous fungal sinusitis; and one had sinonasal sarcoidosis. Conclusion: The preoperative clinical diagnosis can be inaccurate in patienis with CRS and bilateral CRSP. The misdiagnosis is more common in CRSP, including patients with recurrent polyposis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 7 Z9 9 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD MAR-APR PY 2005 VL 19 IS 2 BP 153 EP 157 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 925KF UT WOS:000229051300007 PM 15921214 ER PT J AU Yeh, E Slanetz, P Kopans, DB Rafferty, E Georgian-Smith, D Moy, L Halpern, E Moore, R Kuter, I Taghian, A AF Yeh, E Slanetz, P Kopans, DB Rafferty, E Georgian-Smith, D Moy, L Halpern, E Moore, R Kuter, I Taghian, A TI Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CARCINOMA IN-SITU; GD-DTPA; INDUCTION CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; PATHOLOGICAL CORRELATION; SUSCEPTIBILITY GENE; ENHANCING LESIONS; LOBULAR CARCINOMA; CLIP PLACEMENT; HIGH-RISK AB OBJECTIVE. The objective of our study was to determine the relative accuracy of mammography, sonography, and MRI in predicting residual tumor after neoadjuvant chemotherapy for breast cancer as compared with the gold standards of physical examination and pathology. SUBJECTS AND METHODS. Forty-one women with stage IIB-III palpable breast cancer were prospectively enrolled in a study investigating the effects of sequential single-agent chemotherapy (doxorubicin followed by paclitaxel or vice versa) on tumor imaging. The study cohort consisted of the first 31 patients (age range, 31-65 years; mean, 45 years) who completed the protocol. All underwent physical examination, mammography, sonography, and MRI before and after receiving each neoadjuvant chemotherapeutic drug. Imaging studies were reviewed by two radiologists using conventional lexicons for lesion analysis, and the findings were compared with clinical response and pathology results. RESULTS. Complete, partial, and stable clinical response as defined by clinical examination was seen in 15, 14, and two of the 31 patients, respectively. Agreement rates about the degree of response were 32%, 49%, and 55%, respectively, for mammography, sonography, and MRI compared with clinical evaluation and did not differ statistically. Agreement about the rate of response as measured by clinical examination, mammography, sonography, and MRI compared with the gold standard (pathology) was 19%, 26%, 35%, and 71%, respectively. Of the four, MRI agreed with the gold standard significantly more often (P < 0.002 for all three paired comparisons with MRI). When there was disagreement with the gold standard, none of the four exhibited a significant tendency to either under- or overestimate. CONCLUSION. MRI appears to provide the best correlation with pathology-better than physical examination, mammography, and sonography - in patients undergoing neoadjuvant chemotherapy. However, MRI may overestimate (6%) or underestimate (23%) residual disease in approximately 29% of the patients (95% confidence interval, 14-48%). C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. St Elizabeths Med Ctr, Brighton, MA USA. NYU Med Ctr, New York, NY 10016 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Yeh, E (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,ACC-219, Boston, MA 02114 USA. EM eyeh@partners.org OI Slanetz, Priscilla/0000-0003-1248-5116 NR 63 TC 168 Z9 192 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2005 VL 184 IS 3 BP 868 EP 877 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 901MH UT WOS:000227286100025 PM 15728611 ER PT J AU Hathout, GM Bhidayasiri, R AF Hathout, GM Bhidayasiri, R TI Midbrain ataxia: An introduction to the mesencephalic locornotor region and the pedunculopontine nucleus SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PARKINSONS-DISEASE; LOCOMOTOR REGION; DECEREBRATE CAT; PROJECTIONS; STIMULATION; FAILURE; NEURONS; MONKEY; LEVEL AB OBJECTIVE. Although gait ataxia is usually associated with cerebellar lesions, we review a less familiar cause. We present three patients with dorsal midbrain lesions and correlate these presentations with recent findings in the functional anatomy of the midbrain. CONCLUSION. We suggest that these lesions involve a well-studied but generally unfamiliar area of the dorsal midbrain known as the mesencephalic locomotor region. More specifically, we hypothesize that involvement of the pedunculopontine nucleus, a major component of the mesencephalic locomotor region, may be at least partially responsible for producing midbrain ataxia. C1 W Los Angeles Vet Affairs Med Ctr, Dept Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, PADRECC, Los Angeles, CA 90073 USA. RP Hathout, GM (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Radiol, 11301 Wilshire Blvd,Bldg 500, Los Angeles, CA 90073 USA. EM ghathout@ucla.edu OI Bhidayasiri, Roongroj/0000-0002-6901-2064 NR 20 TC 30 Z9 32 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2005 VL 184 IS 3 BP 953 EP 956 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 901MH UT WOS:000227286100037 PM 15728623 ER PT J AU Lim, R Jaramillo, D Poussaint, TY Chang, YC Korf, B AF Lim, R Jaramillo, D Poussaint, TY Chang, YC Korf, B TI Superficial neurofibroma: A lesion with unique MRI characteristics in patients with neurofibromatosis type 1 SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PERIPHERAL-NERVE SHEATH; PLEXIFORM NEUROFIBROMA; DIFFUSE NEUROFIBROMA; TUMORS; MANAGEMENT AB OBJECTIVE. Our aim was to test the hypothesis that in neurofibromatosis type I (NF1), superficial plexiform neurofibromas have different MRI characteristics than deep plexiform neurofibromas. SUBJECTS AND METHODS. Sixty-six patients (median age, 15 years) with superficial plexiform neurofibromas were compared with 56 patients with deep plexiform neurofibromas (median age, 12 years). All patients underwent axial STIR and coronal or sagittal STIR images. RESULTS. Superficial neurofibromas were more likely to be asymmetric (p = 0.004) and extend to the skin surface) < 0.001). Lesion borders were poorly defined with similar frequency in both superficial and deep groups (77% vs 68%, p = 0.31). The morphology of superficial neurofibromas was more likely diffuse (64% vs 11% p < 0.001), whereas deep neurofibromas were more likely nodular or fascicular. Of neurofibromas that were nodular or fascicular in morphology, superficial lesions had a smaller maximal fascicle-nodule diameter (mean, 10.3 mm) than deep lesions (mean, 13.4 mm) (p = 0.013). Signal characteristics of deep neurofibromas were more likely to be targetlike (75%) compared with superficial neurofibromas (21%) (p < 0.001). Superficial neurofibromas had a smaller mean volume than deep neurofibromas (180 vs 444 cm(3), p = 0.002). CONCLUSION. Unlike the typical targetlike lesions along the course of major nerves seen in deep plexiform lesions, superficial plexiform neurofibromas in NF1 tend to be asymmetric, have nontargetlike signal intensity, lack nodular or fascicular morphology, and are likely to involve skin. C1 Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02150 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. RP Jaramillo, D (reprint author), Childrens Hosp Philadelphia, Dept Radiol, 34th St & Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM jaramillo@email.chop.edu NR 17 TC 31 Z9 37 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 EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2005 VL 184 IS 3 BP 962 EP 968 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 901MH UT WOS:000227286100039 PM 15728625 ER PT J AU vanSonnenberg, E Shankar, S Parker, L Cheung, L Morrison, PR Silverman, SG Igelhart, D AF vanSonnenberg, E Shankar, S Parker, L Cheung, L Morrison, PR Silverman, SG Igelhart, D TI Palliative radiofrequency ablation of a fungating, symptomatic breast lesion SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CARCINOMA; CANCER C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiol, Boston, MA 02115 USA. Univ Massachusetts, Mem Med Ctr, Worcester, MA 01655 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Med,Div Breast Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Surg, Boston, MA 02115 USA. RP vanSonnenberg, E (reprint author), Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. EM ericvansonnenberg@yahoo.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2005 VL 184 IS 3 SU S BP S126 EP S128 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 904UI UT WOS:000227522800045 PM 15728004 ER PT J AU Hornick, JL Lauwers, GY Odze, RD AF Hornick, JL Lauwers, GY Odze, RD TI Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE bile duct adenoma; hamartoma; pancreatic cancer; liver tumors; immunohistochemistry ID HEPATOCELLULAR-CARCINOMA; CARCINOEMBRYONIC ANTIGEN; HER-2/NEU EXPRESSION; PROSTATE-CANCER; MARKER; MESOTHELIN; P53; CHOLANGIOCARCINOMA; CYTOKERATIN-20; NEOPLASMS AB Not uncommonly, bile duct adenomas (BDAs) and hamartomas (BDHs) of the liver may be difficult to distinguish from metastatic well-differentiated ductal adenocarcinoma of the pancreas. However, this distinction is critical for proper staging and patient management. The primary purpose of this Study was to determine if a panel of immunohistochemical stains can help distinguish BDA or BDH from metastatic pancreatic adenocarcinoma in the liver. Routinely processed tissue sections from 25 BDA, 10 BDH, 25 metastatic pancreatic adenocarcinomas to the liver and 6 cases each of metastatic colorectal, breast, and lung adenocarcinomas were immunohistochemically stained for CK7, CK8/CK18, CK19, CK20, p53, p63, TAG-72, monoclonal CEA (mCEA), polyclonal CEA (pCEA), HER-2/neu, AMACR (alpha-methylacyl-CoA racemase), Dpc4 (Smad4), and mesothelin. The slides were evaluated in a blinded fashion, and the results were compared between the benign and malignant lesions. Significantly more (P<0.05) metastatic pancreatic adenocarcinomas were positive for CK20 (76%), p53 (60%), TAG-72 (88%), mCEA (92%), HER2/neu (40%), and mesothelin (64%) and showed loss of Dpc4 (44%), in comparison to BDA (CK20, 40%; p53, 0%; TAG-72, 0%; mCEA, 0%, HER2/neu, 12%; mesothelin, 0%; loss of Dpc4, 0%) or BDH (CK20, 10%; p53, 0%; TAG-72, 0%; mCEA, 10%; HER2/neu, 0%; mesothelin 0%; loss of Dpc4, 0%). Of these antibodies, p53, TAG-72, mCEA, loss of Dpc4, and mesothelin had the highest specificity for pancreatic adenocarcinoma, with mCEA having the highest sensitivity (92%). No significant differences were observed in the degree of CK7, CK8/CK18, CK19, or pCEA expression between the three types of lesions. Although none of the BDA or BDH was positive for either p63 or AMACR, two of the metastatic pancreatic adenocarcinomas (8%) were positive for each of these peptides (P>0.05). For nonpancreatic adenocarcinomas, mCEA showed a reasonably high sensitivity and 100% specificity in the differential diagnosis versus BDA. Immunohistochemical expression of p53, TAG-72, mCEA, mesothelin, and loss of Dpc4 can help distinguish metastatic pancreatic adenocarcinoma in the liver from BDA or BDH. Although p63 and AMACR are also specific for pancreatic adenocarcinoma, their low sensitivity limits their use in clinical practice. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Odze, RD (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM rodze@partners.org NR 45 TC 46 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2005 VL 29 IS 3 BP 381 EP 389 DI 10.1097/01.pas.0000149710.01559.fe PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 902IW UT WOS:000227349300013 PM 15725808 ER PT J AU Fleshman, RL Wasman, JK Bodner, DG Young, RH MacLennan, GT AF Fleshman, RL Wasman, JK Bodner, DG Young, RH MacLennan, GT TI Mesodermal adenosarcoma of the testis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE mesodermal; adenosarcoma; testis ID CLINICOPATHOLOGICAL ANALYSIS; MULLERIAN ADENOSARCOMA; SEMINAL-VESICLE; TUMORS AB Biphasic neoplasms with a benign to atypical epithelial component and a usually low-grade malignant stromal component have been reported in various sites, probably being best known for their occurrence in the uterine corpus (mullerian adenosarcoma). We report a tumor of this type that occurred in the testis of a 76-year-old man and, to our knowledge, is the first mesodermal adenosarcoma reported at this site. The patient had scrotal swelling for many years with a pronounced increase in the swelling over the past 2 years. A large complex solid-cystic testicular tumor was evident on ultrasound, and examination of a radical orchiectomy specimen showed a 6.5-cm mass. On microscopic examination, the neoplasm had a phyllodes-like appearance with bland cuboidal to flattened epithelium covering polypoid fronds, and lining glands and cysts. The stroma varied from cellular, particularly where it condensed around the glands and cysts, to hypocellular and hyalinized. It was immunoreactive for muscle specific actin, CD10, and to a lesser degree, desmin. This case expands the known sites where mesodermal adenosarcoma may occur. The histogenesis is speculative, but possible options are discussed. C1 Case Western Reserve Univ, Inst Pathol, Dept Pathol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Inst Pathol, Dept Urol, Cleveland, OH USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP MacLennan, GT (reprint author), Case Western Reserve Univ, Inst Pathol, Dept Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. EM gtm2@cwru.edu NR 9 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2005 VL 29 IS 3 BP 420 EP 423 DI 10.1097/01.pas.0000152132.66116.47 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA 902IW UT WOS:000227349300019 PM 15725814 ER PT J AU Streblow, DN Kreklywich, CN Smith, P Soule, JL Meyer, C Yin, M Beisser, P Vink, C Nelson, JA Orloff, SL AF Streblow, DN Kreklywich, CN Smith, P Soule, JL Meyer, C Yin, M Beisser, P Vink, C Nelson, JA Orloff, SL TI Rat cytomegalovirus-accelerated transplant vascular sclerosis is reduced with mutation of the chemokine-receptor R33 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE chemokine receptor; cytomegalovirus; transplant vascular sclerosis (TVS); transplant vasculopathy ID PROTEIN-COUPLED RECEPTOR; CHRONIC REJECTION; MURINE CYTOMEGALOVIRUS; ALLOGRAFT ARTERIOSCLEROSIS; HERPESVIRUS SAIMIRI; CELL-PROLIFERATION; CARDIAC ALLOGRAFTS; AORTIC ALLOGRAFTS; HEART-TRANSPLANTS; VIRAL-INFECTION AB Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Deltar33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 x 10(5) pfu RCMV or RCMV-Deltar33 on postoperative day (POD) 1. Grafts from RCMV-Deltar33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Deltar33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Deltar33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-receptor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration. C1 Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97239 USA. Univ Maastricht, Dept Med Microbiol, Maastricht, Netherlands. RP Streblow, DN (reprint author), Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. EM streblow@ohsu.edu FU NHLBI NIH HHS [HL 66238-01, HL71695, HL65754] NR 46 TC 44 Z9 46 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2005 VL 5 IS 3 BP 436 EP 442 DI 10.1111/j.1600-6143.2004.00711.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 896UB UT WOS:000226958200006 PM 15707397 ER PT J AU Kalman, D Morissette, SB George, TP AF Kalman, D Morissette, SB George, TP TI Co-morbidity of smoking in patients with psychiatric and substance use disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; METHADONE-MAINTENANCE PATIENTS; COGNITIVE-BEHAVIORAL THERAPY; TREATING CIGARETTE-SMOKING; PURSUIT EYE-MOVEMENTS; MAJOR DEPRESSION; CESSATION TREATMENT; ALCOHOL DEPENDENCE; NICOTINE DEPENDENCE; SCHIZOPHRENIC-PATIENTS AB This article reviews cigarette smoking in patients with psychiatric disorders (PD) and substance use disorders (SUD). Rates of smoking are approximately 23% in the US population but approximately two- to four-fold higher in patients with PD and IUD. Many remaining smokers have had repeated smoking cessation failures, possibly due to the presence of co-morbid PD and SUDS. There is modest, evidence-based support for effective treatment interventions for nicotine addiction in PD and SUD. Further research is needed to increase our understanding of nicotine addiction in PD and SUD and develop more effective treatment interventions. C1 Yale Univ, Sch Med,Dept Psychiat, Div Subst Abuse,Program Res Smokers Mental Illnes, Subst Abuse Ctr,Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, Anxiety Disorders Clin & Psychol Serv, Boston, MA USA. RP George, TP (reprint author), Yale Univ, Sch Med,Dept Psychiat, Div Subst Abuse,Program Res Smokers Mental Illnes, Subst Abuse Ctr,Connecticut Mental Hlth Ctr, Room S-109,34 Park St, New Haven, CT 06519 USA. EM tony.george@yale.edu FU NIDA NIH HHS [R29 DA011713, K02 DA016611, K02-DA-16611, K23 DA016376, K23-DA-16376, R01 DA013672, R01 DA014039, R01 DA015757, R01-DA-13672, R01-DA-14039, R01-DA-15757, R29-DA-11713] NR 164 TC 276 Z9 280 U1 5 U2 18 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR-APR PY 2005 VL 14 IS 2 BP 106 EP 123 DI 10.1080/10550490590924728 PG 18 WC Substance Abuse SC Substance Abuse GA 922CY UT WOS:000228814700002 PM 16019961 ER PT J AU Wilens, TE Hahesy, AL Biederman, J Bredin, E Tanguay, S Kwon, A Faraone, SV AF Wilens, TE Hahesy, AL Biederman, J Bredin, E Tanguay, S Kwon, A Faraone, SV TI Influence of parental SUD and ADHD on ADHD in their offspring: Preliminary results from a pilot-controlled family study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HIGH-RISK CHILDREN; COCAINE ABUSERS; SUBSTANCE-ABUSERS; PSYCHOPATHOLOGY; ALCOHOLISM; ADOLESCENTS; ACHIEVEMENT; PREVALENCE AB As part of a pilot-controlled family-based study of the children of parents with and without substance use disorders (SUD), the influence of parental SUD and ADHD on the risk for ADHD in offspring was evaluated. Using structured psychiatric interviews, 96 families, (183 youth; mean age 11.6 years) were assessed. To evaluate the effect of parental ADHD and SUD, the offspring were stratified into four groups based on parental status. children of parents with neither ADHD nor SUD, children of parents with SUD only, children of parents with ADHD only, and children of parents with both ADHD and SUD. Using generalized estimating equation models, parental SUD and ADHD were used to predict ADHD in the offspring. The rate of children with ADHD increased among children of parents with neither disorder (3%), children of parents with SUD (13%), children of parents with ADHD (25%), and children of parents with both ADHD and SUD (50%) (p =.001). Children of parents with ADHD or ADHD plus SUD were more likely to have ADHD in comparison to children of parents with neither diagnosis (P < 0.05). Children of parents with ADHD plus SUD were at greater risk of ADHD in comparison to children of parents with SUD only (p = 0.01). Despite the small sample size, the results of this study seem to suggest that the offspring of SUD or ADHD parents are at elevated risk for ADHD compared to controls. The offspring of parents with both ADHD and SUD appear to be at the highest risk for ADHD, highlighting the need for careful screening of this group of youth for ADHD. Replication studies clarifying the nature and strength of the association are necessary. C1 Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Pediat Psychopharmacol Res YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [DA14419, DA-R2911315, DA11929, DA12945]; NIMH NIH HHS [MH-K2001175A] NR 42 TC 15 Z9 15 U1 1 U2 31 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR-APR PY 2005 VL 14 IS 2 BP 179 EP 187 DI 10.1080/10550490590924872 PG 9 WC Substance Abuse SC Substance Abuse GA 922CY UT WOS:000228814700007 PM 16019966 ER PT J AU Law, B Hsiao, JK Bugge, TH Weissleder, R Tung, CH AF Law, B Hsiao, JK Bugge, TH Weissleder, R Tung, CH TI Optical zymography for specific detection of urokinase plasminogen activator activity in biological samples SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE optical zymography; urokinase; fluorescence; probe ID COLON-CARCINOMA CELLS; MATRIX METALLOPROTEINASES; PROTEOLYTIC ACTIVITY; POLYACRYLAMIDE GELS; PROTEASE ACTIVITY; CATHEPSIN-D; COLLAGENASE; INHIBITORS; INVASION; CHARACTERIZE AB Zymography techniques are routinely used to quantify proteolytic activity. In the current study, we describe an optical zymographic procedure that specifically detects urokinase-type plasminogen activator (uPA) activity in biological samples. The method employs a synthetic polymeric uPA fluorescent probe, which is copolymerized in sodium dodecyl sulfate (SDS)-polyacrylamide gel. Following electrophoresis and renaturation, enzymatic digestions of the substrate in 50 mM of Tris buffer at pH 7.4 generates fluorescence emission at 695 nm. The enzymatic activities can be analyzed directly by conventional gel imaging systems with a detection limit of 40 pg. This protocol is fast (hours) and does not require staining and destaining steps. The procedure is independent of plasminogen and, therefore, can efficiently distinguish the active two-chain uPA from its proenzyme. Densitometry analysis demonstrated a highly correlative relationship (r(2)=0.999) between the amount of uPA (over the range of 0.1-8.0 ng) and the average intensity of the fluorescent band. We were able to directly measure uPA activities in different cancer cell lines. This newly developed technique could be expanded to nearly all proteases, including the ones that cannot be analyzed by traditional zymography. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Natl Inst Dent & Craniofacial Res, Proteases Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R01-CA99385, N01-CO17016, P50-CA86355] NR 36 TC 15 Z9 16 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 1 PY 2005 VL 338 IS 1 BP 151 EP 158 DI 10.1016/j.ab.2004.11.039 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 900OA UT WOS:000227223000018 PM 15707946 ER PT J AU Lecamwasam, HS Hess, D Brown, R Kwolek, CJ Bigatello, LM AF Lecamwasam, HS Hess, D Brown, R Kwolek, CJ Bigatello, LM TI Diaphragmatic paralysis after endovascular Stent grafting of a thoracoabdominal aortic aneurysm SO ANESTHESIOLOGY LA English DT Article ID REPAIR; OPERATIONS; PRESSURE C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Resp Care Serv, Div Pulm & Crit Care Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Bigatello, LM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Resp Care Serv, Div Pulm & Crit Care Med, 55 Fruit St, Boston, MA 02114 USA. EM lbigatello@partners.org NR 14 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2005 VL 102 IS 3 BP 690 EP 692 DI 10.1097/00000542-200503000-00032 PG 3 WC Anesthesiology SC Anesthesiology GA 901IW UT WOS:000227277200031 PM 15731612 ER PT J AU Gordon, JA AF Gordon, JA TI The science of common sense: Integrating health and human services in the hospital emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency, Boston, MA 02115 USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Clin 115, Boston, MA 02114 USA. EM jgordon3@partners.org NR 9 TC 2 Z9 2 U1 2 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2005 VL 45 IS 3 BP 251 EP 252 DI 10.1016/j.annemergmed.2004.10.037 PG 2 WC Emergency Medicine SC Emergency Medicine GA 902MC UT WOS:000227360200004 PM 15726046 ER PT J AU Kline, JA Novobilski, AJ Kabrhel, C Richman, PB Courtney, DM AF Kline, JA Novobilski, AJ Kabrhel, C Richman, PB Courtney, DM TI Derivation and validation of a Bayesian network to predict pretest probability of venous thromboembolism SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID SUSPECTED PULMONARY-EMBOLISM; EMERGENCY-DEPARTMENT; CLINICAL-MODEL; D-DIMER; UTILITY; LIKELIHOOD; DIAGNOSIS; CRITERIA; US AB Study objective: A Bayesian network can estimate a numeric pretest probability of venous thromboembolism on the basis of values of clinical variables. We determine the accuracy with which a Bayesian network can identify patients with a low pretest probability of venous thromboembolism, defined as less than or equal to 2%. Methods: Using commercial software, we derived a population of Bayesian networks from 25 input variables collected on 3,145 emergency department (ED) patients with suspected venous thromboembolism who underwent standardized testing, including pulmonary vascular imaging, and 90-day follow-up (11.0% of patients were venous thromboembolism positive). The best-fit Bayesian network was selected using a genetic algorithm. The selected Bayesian network was tested in a validation population of 1,423 ED patients prospectively evaluated for venous thromboembolism, including 90-day follow-up (8.0% were venous thromboembolism positive). The Bayesian network probability estimate was normalized to a score of 0% to 100%. Results: Of 1,423 patients in the validation cohort, 711 (50%; 95% confidence interval [CI] 47% to 52%) had a score less than or equal to 2% that predicted a low pretest probability. Of these 711 patients, 700 (98.5%; 95% CI 97.2% to 99.2%) had no venous thromboembolism at follow-up. Conclusion: A Bayesian network, derived and independently validated in ED populations, identified half of the validation cohort as having a low pretest probability (less than or equal to 2%); 98.5% of these patients were correctly classified by the network. C1 Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28323 USA. Univ Tennessee, Dept Comp Sci, Chattanooga, TN USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Mayo Clin Phoenix, Dept Emergency Med, Scottsdale, AZ USA. Northwestern Mem Hosp, Div Emergency Med, Chicago, IL USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, POB 32861, Charlotte, NC 28323 USA. EM jkline@carolina.rr.com OI Kabrhel, Christopher/0000-0002-8699-7176 NR 23 TC 17 Z9 17 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2005 VL 45 IS 3 BP 282 EP 290 DI 10.1016/j.annemergmed.2004.08.036 PG 9 WC Emergency Medicine SC Emergency Medicine GA 902MC UT WOS:000227360200009 PM 15726051 ER PT J AU Singer, AJ Camargo, CA Lampell, M Lewis, L Nowak, R Schafermeyer, RW O'Neil, B AF Singer, AJ Camargo, CA Lampell, M Lewis, L Nowak, R Schafermeyer, RW O'Neil, B TI A call for expanding the role of the emergency physician in the care of patients with asthma SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID INHALED CORTICOSTEROIDS; PROSPECTIVE MULTICENTER; HOSPITAL ADMISSION; EDUCATION-PROGRAM; CONTROLLED-TRIAL; MANAGEMENT; CHILDREN; THERAPY; VISITS; METAANALYSIS C1 SUNY Stony Brook, Dept Emergency Med, Stony Brook, NY 11794 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Univ Rochester, Dept Emergency Med, Sch Med, Pittsford, NY USA. Washington Univ, Dept Emergency Med, St Louis, MO USA. Case Western Reserve Univ, Dept Emergency Med, Grosse Pointe Pk, MI USA. Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. RP Singer, AJ (reprint author), SUNY Stony Brook, Dept Emergency Med, HSC L3-058, Stony Brook, NY 11794 USA. EM adam.singer@stonybrook.edu NR 45 TC 11 Z9 11 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2005 VL 45 IS 3 BP 295 EP 298 DI 10.1016/j.annemergmed.2004.09.024 PG 4 WC Emergency Medicine SC Emergency Medicine GA 902MC UT WOS:000227360200011 PM 15726053 ER PT J AU Delaunoit, T Alberts, SR Sargent, DJ Green, E Goldberg, RM Krook, J Fuchs, C Ramanathan, RK Williamson, SK Morton, RF Findlay, BP AF Delaunoit, T Alberts, SR Sargent, DJ Green, E Goldberg, RM Krook, J Fuchs, C Ramanathan, RK Williamson, SK Morton, RF Findlay, BP TI Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741 SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; colorectal cancer; resection ID MULTICENTER RANDOMIZED-TRIAL; LIVER METASTASES; HEPATIC METASTASES; NEOADJUVANT CHEMOTHERAPY; SURGICAL RESECTION; 1ST-LINE TREATMENT; PULMONARY METASTASES; LUNG METASTASES; FOLINIC ACID; FLUOROURACIL AB Background: Fluorouracil (5-FU), oxaliplatin and irinotecan combinations improve time to tumor progression (TTP), objective response and overall survival (OS) in patients with metastatic colorectal cancer (MCRC). Here we identify and describe patients treated on Intergroup study N9741 who initially had inoperable MCRC, but who obtained sufficient chemotherapeutic benefit to allow removal of their metastatic disease. Patients and methods: Patient research records in study arms (A) irinotecan/5-FU/Ieucovorin (LV) (IFL, n=264), (F) oxaliplatin/5-FU/LV (FOLFOX4, n=267) and (G) oxaliplatin/irinotecan (IROX, n=265) were reviewed. TTP and median OS were calculated. Results: Twenty-four (3.3%) of 795 randomized patients underwent curative metastatic disease resection [hepatectomy, 16; radiofrequency-ablation (RFA), six; lung resection, two]. Twenty-two out of 24 (92%) resected patients received an oxaliplatin-based regimen (FOLFOX4, 11; IROX, 11). Seven patients (29.2%) remain disease-free; relapses occurred mainly in the resected organ. Median OS in resected patients is 42.4 months, and median TTP is 18.4 months. All six patients treated with RFA have recurred. Four out of five (80%) patients who received chemotherapy following resection are disease-free. Conclusions: Resection of metastatic disease after chemotherapy is possible in a small but important subset of patients with MCRC, particularly after receiving an oxaliplatin-based chemotherapy regimen, with encouraging OS and TTP observed in these highly selected patients. C1 Mayo Clin & Mayo Fdn, Canc Ctr Stat, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Oncol, Rochester, MN 55905 USA. Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. Duluth Clin, Duluth, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Iowa Oncol Res Assoc CCOP, Des Moines, IA USA. Natl Canc Inst Canada, St Catharines, ON, Canada. RP Sargent, DJ (reprint author), Mayo Clin & Mayo Fdn, Canc Ctr Stat, Kahler 1A,200 1st St SW, Rochester, MN 55905 USA. EM sargent.daniel@mayo.edu RI Goldberg , Richard/M-1311-2013 FU NCI NIH HHS [CA25224] NR 34 TC 100 Z9 105 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2005 VL 16 IS 3 BP 425 EP 429 DI 10.1093/annone/mdi092 PG 5 WC Oncology SC Oncology GA 905KQ UT WOS:000227567400013 PM 15677624 ER PT J AU Feng, J Bianchi, C Li, JY Sellke, FW AF Feng, J Bianchi, C Li, JY Sellke, FW TI Bradykinin preconditioning preserves coronary microvascular reactivity during cardioplegia-reperfusion SO ANNALS OF THORACIC SURGERY LA English DT Article ID ISCHEMIA-REPERFUSION; RABBIT HEART; RAT-HEART; PROTECTION; MYOCARDIUM; INJURY; ENDOTHELIUM; ADENOSINE; PATHWAYS AB Background. Alterations of microvascular reactivity reduce myocardial perfusion after ischemic cardioplegia. We hypothesized that bradykinin preconditioning (BKPC) would preserve endothelium-dependent microvascular responses and improve myocardial function after cardioplegic ischemia-reperfusion. Methods. Rabbit hearts were perfused with Krebs-Henseleit buff er (KHB). The hearts were arrested for 60 minutes with moderately cold (25degreesC) crystalloid cardioplegia (MCCP, n = 8) or with cold (0degrees to 4degreesC) crystalloid cardioplegia (CCCP) (n = 6). The BKPC hearts received a 10-minute coronary infusion of 10(-8) M BK-enriched KHB, followed by a 5-minute recovery period, and then were arrested for 60 minutes with MCCP (BKPC + MCCP, n = 8) or with CCCP (BKPC + CCCP, n = 6). The hearts were reperfused for 30 minutes with KHB. Six control hearts were perfused with KHB for 90 minutes without cardioplegia-ischemia. Left ventricle performance was measured, and in vitro relaxation responses of precontracted coronary arterioles (internal diameter, 80 to 150 mum) were obtained in a pressurized no-flow state. Results. Ischemic arrest with MCCP or CCCP markedly reduced endothelium-dependent relaxation to adenosine 5'-diphosphate, substance P, and calcium ionophore (A23187). Both MCCP and CCCP significantly enhanced contractile responses to U46619 (10(-7) M), a thromboxane A(2) analogue, compared with control (p < 0.05). In contrast, BKPC significantly improved the recovery of endothelium-dependent relaxation to adenosine 5'-diphosphate, substance P, and A23187 compared with MCCP or CCCP, respectively. BKPC reduced the contractile responses to U46619 compared with MCCP or CCCP. BKPC also improved postischemic performance compared with MCCP or CCCP alone (p < 0.05). Conclusions. BKPC preserves endothelium-dependent microvascular responses and prevents the hypercontractility to U46619. These effects may provide increased coronary perfusion and prevent arteriolar spasm after open heart surgery. They suggest that BK preconditions the coronary microvasculature during cardiovascular surgery. C1 Harvard Univ, BIDMC, Div Cardiovasc Surg, Dept Surg,Sch Med, Boston, MA 02215 USA. RP Sellke, FW (reprint author), Harvard Univ, BIDMC, Div Cardiovasc Surg, Dept Surg,Sch Med, LMOB 2A,110 Francis St, Boston, MA 02215 USA. EM fsellke@caregroup.harvard.edu RI bianchi, cesario/H-6238-2012 FU NHLBI NIH HHS [HL-46716, HL-69024] NR 30 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2005 VL 79 IS 3 BP 911 EP 916 DI 10.1016/j.athorascur.2004.09.017 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 903GR UT WOS:000227414400024 PM 15734404 ER PT J AU Crawford, SA Fiebelkorn, KR Patterson, JE Jorgensen, JH AF Crawford, SA Fiebelkorn, KR Patterson, JE Jorgensen, JH TI International clone of Neisseria meningitidis serogroup A with tetracycline resistance due to tet(B) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PENICILLIN; DISEASE; SUSCEPTIBILITY; GENES; SPAIN AB Thirteen Neisseria meningitidis clinical isolates from Africa, Asia, and the United States for which the tetracycline MICs were elevated (greater than or equal to8 mug/ml) were examined for 14 recognized resistance genes. Only the drug efflux mechanism encoded by tet(B) was detected. All isolates were in serogroup A, belonged to complex ST-5, and were closely related by pulsed-field gel electrophoresis analysis. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA. RP Jorgensen, JH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Jorgensen@uthscsa.edu NR 20 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2005 VL 49 IS 3 BP 1198 EP 1200 DI 10.1128/AAC.49.3.1198-1200.2005 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 902FJ UT WOS:000227339500049 PM 15728926 ER PT J AU Yan, X Shen, H Wang, LP Jiang, HJ Wu, XQ Wang, J Hu, D Wolf, D Yang, Z Dao, M Ni, PH Zhang, CS AF Yan, X Shen, H Wang, LP Jiang, HJ Wu, XQ Wang, J Hu, D Wolf, D Yang, Z Dao, M Ni, PH Zhang, CS TI External Qi and Qi water of Yan Xin life science technology (YXLST) potently inhibit-HIV-1 replication SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 18th International Conference on Antiviral Research CY APR 11-14, 2005 CL Barcelona, SPAIN SP Int Soc Antiviral Res C1 New Med Sci res Inst, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Boston, MA USA. Univ Connecticut, Storrs, CT USA. McMaster Univ, Hamilton, ON, Canada. RI Dao, Ming/B-1602-2008; Hu, Dan/D-9642-2015 NR 0 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 2005 VL 65 IS 3 BP A47 EP A48 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 911GF UT WOS:000227989900042 ER PT J AU McNeill, MR Matthews, CT Hula, WD Doyle, PJ Rubinsky, HJ Fossett, TRD AF McNeill, MR Matthews, CT Hula, WD Doyle, PJ Rubinsky, HJ Fossett, TRD TI A dual-task tool for quantifying normal comprehension of aphasic connected speech production: A constructive replication SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Clinical Aphasiology Conference CY 2004 CL Park City, TX ID DIVIDED-ATTENTION; RESOURCE-ALLOCATION; MULTIPLE RESOURCES; MANUAL TRACKING; PERFORMANCE; INDIVIDUALS; SENSITIVITY; DIFFICULTY; LANGUAGE; STIMULI AB Background: Deficits of attention or its control secondary to brain damage have been proposed as all or part of the underlying mechanisms for the linguistic impairments that characterise aphasia (Clark & Robin, 1995; Granier, Robin, Shapiro, Peach, & Zimba, 2000; McNeil, 1982, 1988; McNeil, Odell, & Tseng, 1991; Murray, Holland, & Beeson, 1997a; Tseng, McNeil, & Milenkovic, 1993). McNeil, Doyle, Hula, Rubinsky, Fossett, and Matthews (2004) developed a set of tasks to quantify the difficulty that normal listeners have in understanding the language production of persons with varying amounts of aphasia. In their dual-task study, a significant decrement was found in the visual-manual tracking accuracy of normal older individuals while concurrently listening to the connected language of a person with moderate, as compared to mild, aphasia. No performance costs were observed on the listening tasks across three tracking difficulty levels. Possible reasons for the unidirectional performance cost were speculated and the present study was designed to investigate one of them. Aims: Using the same story comprehension task used in the previous study and the same visual-manual tracking task, but increased in difficulty, this study sought to investigate whether the increased demands of the tracking task were sufficient to elicit a concurrent cost on story comprehension performance. Methods & Procedures: A total of 24 normal participants performed the tracking and story comprehension tasks concurrently and in isolation. Story retell performance was evaluated within subjects across two tracking difficulty levels (easy and hard) and tracking performance was evaluated between subjects across three story difficulty levels (no story, mild difficulty, and moderate difficulty). Outcomes & Results: Tracking performance varied significantly across story task difficulty in the easy tracking condition, with participants demonstrating better tracking performance in the mild story condition than in either the moderate story or no story conditions. None of the comparisons made with the harder tracking condition reached significance. There was no effect of tracking difficulty on story comprehension as measured by subsequent story retell performance. Conclusions: The findings from this study replicate the findings from the McNeil et al. (2004) study that these dual-tasks show a reliable cost of story difficulty on concurrent tracking performance. Contrary to predictions, no effect of tracking difficulty on story retell performance was found, despite the increased tracking difficulty used compared to the previous study. While this finding does diminish the probability that insufficient tracking task difficulty was the source of the unidirectional costs in the previous study, it leaves a number of alternative explanations for the findings viable and unaddressed. C1 Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP McNeill, MR (reprint author), Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. EM meneil+@pitt.edu NR 42 TC 3 Z9 3 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAR-MAY PY 2005 VL 19 IS 3-5 BP 473 EP 484 DI 10.1080/02687030444000895 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 931IL UT WOS:000229478900022 ER PT J AU Ahn, A Yang, CH Wax, A Popescu, G Fang-Yen, C Badizadegan, K Dasari, RR Feld, MS AF Ahn, A Yang, CH Wax, A Popescu, G Fang-Yen, C Badizadegan, K Dasari, RR Feld, MS TI Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer SO APPLIED OPTICS LA English DT Article AB Harmonic phase-dispersion microscopy (PDM) is a new imaging technique in which contrast is provided by differences in refractive index at two harmonically related wavelengths. We report a new configuration of the harmonic phase-dispersion microscope in a Mach-Zehnder geometry as an instrument for imaging biological samples. Several improvements on the earlier design are demonstrated, including a single-pass configuration and acousto-optic modulators for generating the heterodyne signals without mechanical arm scanning. We demonstrate quantitative phase-dispersion images of test structures and biological samples. (C) 2005 Optical Society of America. C1 MIT, GR Harrison Spect Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ahn, A (reprint author), MIT, GR Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM minwah@mit.edu RI Wax, Adam/A-4760-2008; OI Wax, Adam/0000-0002-1827-5112; Fang-Yen, Christopher/0000-0002-4568-3218 FU NCRR NIH HHS [P41-RR02594-18] NR 4 TC 13 Z9 14 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD MAR 1 PY 2005 VL 44 IS 7 BP 1188 EP 1190 DI 10.1364/AO.44.001188 PG 3 WC Optics SC Optics GA 903XT UT WOS:000227459600010 PM 15765698 ER PT J AU Reger, MA Martin, DJ Cole, SL Strauss, G AF Reger, MA Martin, DJ Cole, SL Strauss, G TI The relationship between plasma viral load and neuropsychological functioning in HIV-1 infection SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE HIV; viral load; HIV RNA; cognition; neuropsychological functioning ID IMMUNODEFICIENCY-VIRUS INFECTION; CEREBROSPINAL-FLUID; RNA LEVELS; TYPE-1 RNA; DEMENTIA; ENCEPHALITIS; PATHOGENESIS; IMPAIRMENT; AIDS AB Plasma viral load is helpful in monitoring systemic HIV infection but the relationship between plasma viral load and CNS functioning remains unclear. Equivocal results have been reported on the relationship between plasma viral load and cognitive functioning. The present study tested cognitive functions with a standardized neuropsychological battery consisting of 28 test scores. Participants (N = 140) were grouped into undetectable (<400 copies), low (401-10,000 copies), or moderate (10,001-100,000 copies) viral load groups. Statistical analyses (MANOVA and MANCOVA) revealed no differences in neuropsychological test performance between the viral load groups. Fairly healthy patients with moderate plasma viral loads do not appear to show increased neuropsychological dysfunction. CSF viral load may be more helpful in evaluating cognitive correlates of HIV encephalitis. (C) 2004 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Sch Med, Res & Educ Inst,Dept Psychiat & Biobehav Sci, Torrance, CA 90509 USA. RP Martin, DJ (reprint author), Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Sch Med, Res & Educ Inst,Dept Psychiat & Biobehav Sci, 1000 W Carson St,Box 488, Torrance, CA 90509 USA. EM djmartin@ucla.edu FU NIMH NIH HHS [1 R01 MH62966-01A1]; PHS HHS [5 H97 HA00054] NR 17 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR PY 2005 VL 20 IS 2 BP 137 EP 143 DI 10.1016/j.acn.2004.03.009 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 903AU UT WOS:000227398600001 PM 15708723 ER PT J AU Goldstein, G Shemansky, WJ Allen, DN AF Goldstein, G Shemansky, WJ Allen, DN TI Cognitive function in schizoaffective disorder and clinical subtypes of schizophrenia SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE schizophrenia; mood disorder; cognitive heterogeneity ID HETEROGENEITY AB Cognitive studies of patients with Schizoaffective Disorder typically indicate that the cognitive function of these patients resembles that of patients with Schizophrenic Disorder more than it does patients with nonpsychotic Mood Disorder. In this study patients with Schizoaffective Disorder were compared with patients with Paranoid, Undifferentiated and Residual clinical subtypes on a number of measures of cognitive function. Multivariate analyses of variance indicated that the cognitive function of Schizoaffective and Paranoid patients had more intact cognitive function that did Undifferentiated and Residual patients. Application of cluster analysis indicated that there were relative high percentages of Schizoaffective and Paranoid patients in a "Neuropsychologically Normal" cluster. It was concluded that Schizoaffective Disorder as well as other clinical subtypes of schizophrenia are cognitively heterogeneous, and it was suggested that a subgroup of patients with Schizoaffective Disorder may not differ in cognitive ability from patients with nonpsychotic Mood Disorder. (C) 2004 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Res 151R, Pittsburgh, PA 15206 USA. Univ Nevada, Las Vegas, NV 89154 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Res 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM ggold@nb.net NR 10 TC 37 Z9 38 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR PY 2005 VL 20 IS 2 BP 153 EP 159 DI 10.1016/j.acn.2004.03.008 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 903AU UT WOS:000227398600003 PM 15708725 ER PT J AU Shin, LM Wright, CI Cannistraro, PA Wedig, MM McMullin, K Martis, B Macklin, ML Lasko, NB Cavanagh, SR Krangel, TS Orr, SP Pitman, RK Whalen, PJ Rauch, SL AF Shin, LM Wright, CI Cannistraro, PA Wedig, MM McMullin, K Martis, B Macklin, ML Lasko, NB Cavanagh, SR Krangel, TS Orr, SP Pitman, RK Whalen, PJ Rauch, SL TI A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; SCRIPT-DRIVEN IMAGERY; FACIAL EXPRESSIONS; ANTERIOR CINGULATE; PHYSIOLOGICAL-RESPONSES; SYMPTOM PROVOCATION; LOUD TONES; ANXIETY DISORDERS AB Background: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). Objectives: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD. Design: Case-control study. Setting: Academic medical center. Participants: Volunteer sample of 13 men with PTSD (PTSD group) and 13 trauma-exposed men without PTSD (control group). Main Outcome Measures: We used functional magnetic resonance imaging (fMRI) to study blood oxygen- ation level-dependent signal during the presentation of emotional facial expressions. Results: The PTSD group exhibited exaggerated amygdala responses and diminished medial prefrontal cortex responses to fearful vs happy facial expressions. In addition, in the PTSD group, blood oxygenation level-dependent signal changes in the amygdala were negatively correlated with signal changes in the medial prefrontal cortex, and symptom severity was negatively related to blood oxygenation level-dependent signal changes in the medial prefrontal cortex. Finally, relative to the control group, the PTSD group tended to exhibit diminished habituation of fearful vs happy responses in the right amygdala across functional runs, although this effect did not exceed our a priori statistical threshold. Conclusions: These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortex responsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Brigham Behav Neurol Grp, Dept Neurol, Boston, MA 02115 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Vet Affairs Res Serv, Manchester, NH USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM lisa.shin@tufts.edu FU NIMH NIH HHS [MH-60219, MH-64806] NR 59 TC 488 Z9 504 U1 4 U2 52 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2005 VL 62 IS 3 BP 273 EP 281 DI 10.1001/archpsyc.62.3.273 PG 9 WC Psychiatry SC Psychiatry GA 902YC UT WOS:000227391600005 PM 15753240 ER PT J AU Tabatabai, G Baehring, J Hochberg, FH AF Tabatabai, G Baehring, J Hochberg, FH TI Primary amyloidoma of the brain parenchyma SO ARCHIVES OF NEUROLOGY LA English DT Article ID OF-THE-LITERATURE; CENTRAL-NERVOUS-SYSTEM; GASSERIAN GANGLION; CEREBRAL AMYLOIDOMA; LIGHT-CHAIN; SKULL BASE; TUMOR; CT; CNS AB A myloidoma can occur within the brain parenchyma. Periventricular amyloidomas developed in a man aged 69 years as gadolinium-enhancing lesions on magnetic resonance imaging. The lesions were composed of amyloid AL lambda with congophilia resistant to potassium permanganate. There was no evidence of systemic amyloidosis or an underlying inflammatory or neoplastic disorder. C1 Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA. EM fhochberg@partners.org RI Tabatabai, Ghazaleh/A-6365-2015 OI Tabatabai, Ghazaleh/0000-0003-3702-923X NR 28 TC 15 Z9 19 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2005 VL 62 IS 3 BP 477 EP 480 DI 10.1001/archneur.62.3.477 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 903SN UT WOS:000227446000020 PM 15767515 ER PT J AU Seddon, JM Cote, J Page, WF Aggen, SH Neale, MC AF Seddon, JM Cote, J Page, WF Aggen, SH Neale, MC TI The US twin study of age-related macular degeneration - Relative roles of genetic and environmental influences SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; DIETARY-FAT; CLASSIFICATION-SYSTEM; FAMILIAL AGGREGATION; MONOZYGOTIC TWINS; RISK-FACTORS; VITAMIN-C; MACULOPATHY; ASSOCIATION; DISEASE AB Context: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older individuals in many parts of the world. The relative importance of genes and environment in the etiology of this major public health problem is not well understood. Objective: To investigate the impact of genetic and environmental factors. Participants: Living twins in the National Academy of Sciences-National Research Council World War 11 Veteran Twin Registry born between 1917 and 1927. Methods: Twins were surveyed for the known presence of macular degeneration. Enrolled twins underwent a standardized examination and fundus photography. Age-related macular degeneration evaluation was completed for 840 elderly male twins, 2 10 monozygotic and 181 dizygotic complete twin pairs, both concordant and discordant for presence or absence of AMD, and 58 singletons. A bivariate twin model incorporating initial screening ascertainment and age effects was employed to partition variation in liability to AMD and signs of maculopathy into additive genetic, common environment, and unique environment components. Main Outcome Measure: Heritability of AMD grade and signs of maculopathy based on clinical examination and fundus photographs. Results: Of the 840 twins, 331 had no signs of maculopathy and 241 had early signs, while 162 had intermediate AMD and 106 had advanced AMD. Heritability (additive genetic) estimates were significant for overall AMD grade (0.46) and for intermediate (0.67) and advanced (0.71) AMD. Significant unique environmental proportions of variance were also observed for these AMD variables (0.37, 0.19, and 0.24, respectively). Shared or common environmental contributions were not significant (0.05-0.17). For specific macular drusen and retinal pigment epithelial characteristics, significant genetic (0.26-0.71) and unique environmental (0.28-0.64) proportions of variance were detected. Conclusions: Genetic factors play a substantial role in the etiology of AMD and associated macular characteristics, explaining 46% to 71% of the variation in the overall severity of the disease. Environmental factors unique to each twin also contribute to the occurrence of this disease. This quantification of relative genetic and environmental contributions to the development of AMD should guide future research on this important cause of blindness. C1 Massachusetts Eye & Ear Infirm, Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Natl Acad Sci, Natl Res Council, Vet Twin Registry World War 2, Washington, DC 20418 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. RP Seddon, JM (reprint author), Massachusetts Eye & Ear Infirm, Epidemiol Unit, 243 charles St, Boston, MA 02114 USA. EM Johanna_Seddon@meei.harvard.edu RI Neale, Michael/B-1418-2008 FU NEI NIH HHS [EY10012]; NIMH NIH HHS [MH65322, MH01458] NR 56 TC 207 Z9 215 U1 3 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2005 VL 123 IS 3 BP 321 EP 327 DI 10.1001/archopht.123.3.321 PG 7 WC Ophthalmology SC Ophthalmology GA 903SV UT WOS:000227446800002 PM 15767473 ER PT J AU Palmer-Toy, DE Wang, E Winter, WE Soldin, SJ Klee, GG Howanitz, JH Elin, RJ AF Palmer-Toy, DE Wang, E Winter, WE Soldin, SJ Klee, GG Howanitz, JH Elin, RJ TI Comparison of pooled fresh frozen serum to proficiency testing material in College of American Pathologists surveys - Cortisol and immunoglobulin E SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CLINICAL-CHEMISTRY; ACCURACY AB Context.-The College of American Pathologists (CAP) provides proficiency testing (PT) surveys to laboratories around the world. Objectives.-To compare diagnostic assay methods for serum/plasma cortisol and immunoglobulin (Ig) E in terms of their bias and precision, to determine how well CAP PT specimens simulate human serum, and to reassess proficiency test grading criteria in light of these findings. Design.-A participant-blinded, prospective trial. One vial of pooled fresh frozen serum (FFS) and 4 different admixtures of PT material (PTM) were sent to laboratories participating in PT surveys. Participants.-Laboratories providing cortisol (>1000) or IgE (>230) results among the subscribers to the CAP surveys, Ligand (General) 2003, set K/KN-A and Chemistry 2003, set C-C. Main Outcome Measures.-The main outcome measures were (1) bias among laboratories using the same method (peer groups), defined relative to the median of method means (MedMM); (2) imprecision as measured by the SD and coefficient of variation (CV) about each method mean; and (3) total error across laboratories for the FFS cortisol results, defined as [Bias Relative to Reference Method] + 2 SD. Results.-Cortisol method biases, relative to MedMM, ranged from -22% to 9% for the FFS challenge and from -24% to 36% for comparable PTM challenges. The method biases, relative to the reference method, ranged from -3% to 19% for the FFS challenge. The cortisol method CVs ranged from 4.2% to 13.6% for the FFS challenge and from 4.7% to 12.7% for comparable PTM challenges. Total error across laboratories ranged from 1.4 to 6.9 mug/dL (39 to 190 nmol/L) for the FFS challenge. Immunoglobulin E method biases, relative to MedMM, ranged from -8% to 9% for the FFS challenge and from -7% to 5% for comparable PTM challenges. The IgE method CVs ranged from 3.6% to 6.7% for the FFS challenge and from 3.4% to 9.8% for comparable PTM challenges. Conclusions.-The bias for cortisol results was less with FFS than with PTM, but imprecision was comparable. The FFS MedMM was 8.5% higher than the reference value. Fresh frozen serum and PTM bias and imprecision for IgE methods were each less than 10%. Because some of the methods demonstrated greater bias when analyzing PTM than FFS, peer group grading of both these analytes is appropriate. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. Coll Amer Pathologists, Northfield, IL USA. Univ Florida, Shands Hosp, Dept Pathol, Gainesville, FL USA. Georgetown Univ, Sch Med, Childrens Natl Med Ctr, Dept Lab Med, Washington, DC USA. Mayo Clin, Dept Lab Med, Rochester, MN USA. Univ Louisville, Dept Pathol, Louisville, KY 40292 USA. Univ Hosp Brooklyn, State Univ New York Hlth Sci Ctr, Dept Pathol, Brooklyn, NY USA. RP Palmer-Toy, DE (reprint author), Harvard Partners Ctr Genet & Genom, 65 Landowne St,3rd Floor, Cambridge, MA 02139 USA. EM dept@alum.mit.edu NR 9 TC 10 Z9 12 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2005 VL 129 IS 3 BP 305 EP 309 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 903SL UT WOS:000227445800005 PM 15737022 ER PT J AU Steele, BW Wang, E Palmer-Toy, DE Killeen, AA Elin, RJ Klee, GG AF Steele, BW Wang, E Palmer-Toy, DE Killeen, AA Elin, RJ Klee, GG TI Total long-term within-laboratory precision of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone assays based on a College of American Pathologists fresh frozen serum study - Do available methods meet medical needs for precision? SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DRUG-MONITORING SURVEY; CLINICAL-CHEMISTRY; VARIABILITY; ACCURACY AB Context.-It is important that the total long-term precision of laboratory methods meet the medical needs of the patients being served. Objectives.-To determine the long-term within- and between-laboratory variation of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone measurements using commonly available methods and to determine if these variations are within accepted medical needs. Design.-Two vials of pooled frozen serum were mailed 6 months apart to laboratories participating in 2 separate College of American Pathologists surveys. The data from those laboratories that analyzed an analyte in both surveys were used to determine for each method the total variance and the within- and between-laboratory components. Setting.-The study included the A mailing of the 2003 College of American Pathologists Ligand Survey and the C mailing of the Chemistry Survey. Main Outcome Measures.-For each analyte, total variance was partitioned into within- and between-laboratory components for each analytic method. The within-laboratory variations were then compared with imprecision criteria based on biological variation. Participants.-The laboratories that reported results on the same analyte using the same method in both surveys. Results.-For each analyte, the median of the long-term within-laboratory variances of each peer group was 78% to 95% of its total-survey variance, and the median long-term within-laboratory coefficients of variation varied from 5.1% to 7.6%. The number of methods that met within-laboratory imprecision goals based on biological criteria were 5 of 5 for cortisol; 5 of 7 for ferritin; 0 of 7 for thyroxine and free thyroxine; and 8 of 8 for thyroid-stimulating hormone. Conclusions.-For all analytes tested, the total within-laboratory component of variance was the major source of variability in this study. In addition, there are several methods, especially for thyroxine and free thyroxine, that may not meet analytic goals in terms of their imprecision. C1 Univ Miami, Sch Med, Dept Pathol, Miami, FL 33152 USA. Coll Amer Pathologists, Northfield, IL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Partners Ctr Genet & Genom, Cambridge, MA 02138 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Louisville, Dept Pathol & Lab Med, Louisville, KY 40292 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Steele, BW (reprint author), Jackson Mem Hosp, Holtz Ctr, Room 2026,1611 NW 12th Ave, Miami, FL 33136 USA. EM bsteele@med.miami.edu RI Killeen, Anthony/E-4697-2010 OI Killeen, Anthony/0000-0003-1629-9468 NR 15 TC 15 Z9 16 U1 1 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2005 VL 129 IS 3 BP 318 EP 322 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 903SL UT WOS:000227445800007 PM 15737024 ER PT J AU Baldessarini, RJ Faedda, GL Hennen, J AF Baldessarini, RJ Faedda, GL Hennen, J TI Risk of mania with antidepressants SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. RP Baldessarini, RJ (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org NR 4 TC 21 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2005 VL 159 IS 3 BP 298 EP 298 DI 10.1001/archpedi.159.3.298-a PG 1 WC Pediatrics SC Pediatrics GA 902YJ UT WOS:000227392300018 PM 15753278 ER PT J AU Algood, SD Cooper, RA Fitzgerald, SG Cooper, R Boninger, ML AF Algood, SD Cooper, RA Fitzgerald, SG Cooper, R Boninger, ML TI Effect of a pushrim-activated power-assist wheelchair on the functional capabilities of persons with tetraplegia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 27th International Conference of the RESNA CY JUN 18-24, 2004 CL Orlando, FL SP RESNA DE activities of daily living; rehabilitation; tetraplegia; wheelchairs ID MANUAL WHEELCHAIR; PHYSICAL STRAIN; UPPER EXTREMITY; PROPULSION; PERFORMANCE; PARAPLEGIA; PHYSIOLOGY; EFFICIENCY; USERS; PAIN AB Objectives: To test the differences between a pushrim-activated power-assisted wheelchair (PAPAW) and a traditional manual wheelchair while performing common driving activities and to assess their relative merits for people with tetraplegia. Design: Repeated measures. Setting: An activities of daily living (ADL) laboratory within a rehabilitation research center. Participants: Fifteen full-time manual wheelchair users with tetraplegia due to a spinal cord injury. Interventions: Participants propelled both their own manual wheelchairs and a PAPAW 3 times over an ADL course. The order in which the 2 different wheelchairs were presented to the participants was randomized. Main Outcome Measures: Each participant's heart rate was monitored throughout testing by a digital, wireless heart-rate monitor. Time to complete the course was recorded, and participants were surveyed with a visual analog scale after the first, third, fourth, and sixth trials to determine the ease of completing each obstacle and their ergonomic preferences between the 2 wheelchairs. Participants also were observed throughout the trials to determine how much assistance they needed to complete each obstacle course. Results: After using a Bonferroni adjustment, 4 obstacles (carpet, dimple strips, up a ramp, up a curb cut) were rated as being significantly easier (P < .001) to complete when using the PAPAW. Participants also showed a significant decrease in mean heart rate throughout all 3 trials (P = .015, P = .001, P = .003, respectively) when using a PAPAW. The amount of assistance needed by participants, the responses to ergonomic questions, and the overall time to complete the ADL course did not differ significantly between the 2 wheelchairs. Conclusions: For subjects with tetraplegia, PAPAWs have the potential to improve functional capabilities during certain ADLs, especially when propelling up ramps, over uneven surfaces, and over thick carpet. (C) 2005 by American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, VA Rehabil Res & Dev Ctr, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 22 TC 27 Z9 30 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2005 VL 86 IS 3 BP 380 EP 386 DI 10.1016/j.apmr.2004.05.017 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 904DB UT WOS:000227475200003 PM 15759215 ER PT J AU Hughes, RB Robinson-Whelan, S Taylor, HB Petersen, NJ Nosek, MA AF Hughes, RB Robinson-Whelan, S Taylor, HB Petersen, NJ Nosek, MA TI Characteristics of depressed and nondepressed women with physical disabilities SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE depression; disabled persons; rehabilitation; women's health ID SECONDARY CONDITIONS; INVENTORY-II; SYMPTOMS; GENDER; CARE; DISPARITIES; POPULATION; PREVALENCE; RACE; PAIN AB Objectives: To describe the characteristics of depressed versus nondepressed women with disabilities. Design: Survey. Setting: Women were recruited through private and public health clinics and various community organizations. Participants: A sample of 443 predominantly ethnic-minority women, ages 18 to 83 years, with physical disabilities. Interventions: Not applicable. Main Outcome Measure: Beck Depression Inventory-II (BDI-II). Results: Approximately half (51%) of the sample had scores in the mildly depressed range or higher on the BDI-II. Women classified as depressed were more likely to have multiple sclerosis, to be younger, or to have a shorter duration of disability. Only 44% of the women with scores exceeding the BDI-II cutoff for significant depressive symptomatology had received recent treatment for depression, with Hispanic women being the least likely to report receiving treatment. Depressed women reported significantly more health conditions, reflecting common symptoms of depression, conditions linked with depression in the general population, conditions known to be secondary to the primary condition, and conditions known to be common side effects of medications. Depression was not related to functional limitations. Conclusions: Depression is a serious mental health problem facing many women with physical disabilities that does not appear to be adequately addressed by health care professionals. (C) 2005 by American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Baylor Coll Med, Ctr Res Women Disabil, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Rehabil Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res& Dev Serv, Houston, TX USA. RP Hughes, RB (reprint author), Baylor Coll Med, Ctr Res Women Disabil, Dept Phys Med & Rehabil, 6550 Fannin,Ste 1421, Houston, TX 77030 USA. EM rhughes@bcm.tmc.edu FU ODCDC CDC HHS [R04/CCR618805] NR 33 TC 15 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2005 VL 86 IS 3 BP 473 EP 479 DI 10.1016/j.apmr.2004.06.068 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 904DB UT WOS:000227475200019 PM 15759231 ER PT J AU Rask-Madsen, C King, GL AF Rask-Madsen, C King, GL TI Proatherosclerotic mechanisms involving protein kinase C in diabetes and insulin resistance SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE pathophysiology; cell signaling/signal transduction; gene regulation; type 2 diabetes; mechanism of atherosclerosis/growth factors; type 1 diabetes; endothelium/vascular type/nitric oxide ID NITRIC-OXIDE SYNTHASE; HUMAN ENDOTHELIAL-CELLS; LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE-CELLS; HIGH GLUCOSE; NAD(P)H OXIDASE; ANGIOTENSIN-II; GENE-EXPRESSION; ADHESION MOLECULE-1; OXIDATIVE STRESS AB In diabetes and insulin resistance, activation of protein kinase C (PKC) in vascular cells may be a key link between elevated plasma and tissue concentrations of glucose and nonesterified fatty acids and abnormal vascular cell signaling. Initial studies of PKC activation in diabetes focused on microvascular complications, but increasing evidence supports that PKC plays a role in several mechanisms promoting atherosclerosis. This review explains how PKC is thought to be activated in diabetes and insulin resistance through de novo synthesis of diacylglycerol. Furthermore, the review summarizes studies that implicate PKC in promoting proatherogenic mechanisms or inhibiting antiatherogenic mechanisms, including studies of endothelial dysfunction; gene induction and activation of vascular NAD( P) H oxidase; endothelial nitric oxide synthase expression and function; endothelin-1 expression; growth, migration, and apoptosis of vascular smooth muscle cells; induction of adhesion molecules; and oxidized low-density lipoprotein uptake by monocyte-derived macrophages. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02120 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl,Room 4504, Boston, MA 02120 USA. EM george.king@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK59725, R01 DK53105] NR 117 TC 105 Z9 118 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2005 VL 25 IS 3 BP 487 EP 496 DI 10.1161/01.ATV.0000155325.41507.e0 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 900NL UT WOS:000227221500007 PM 15637306 ER PT J AU Saam, T Cai, JM Cai, YQ An, NY Kampschulte, A Xu, D Kerwin, WS Takaya, N Polissar, NL Hatsukami, TS Yuan, C AF Saam, T Cai, JM Cai, YQ An, NY Kampschulte, A Xu, D Kerwin, WS Takaya, N Polissar, NL Hatsukami, TS Yuan, C TI Carotid plaque composition differs between ethno-racial groups - An MRI pilot study comparing mainland Chinese and American Caucasian patients SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; carotid arteries; epidemiology; MRI ID CORONARY-ARTERY CALCIFICATION; HIGH-RESOLUTION MRI; IN-VIVO ACCURACY; RISK-FACTORS; ATHEROSCLEROTIC LESIONS; WHITE SUBJECTS; CLASSIFICATION; HYPERTENSION; PREVALENCE; HEMORRHAGE AB Objective - Ethnicity-based research may identify new clues to the pathogenesis of atherosclerotic disease. Therefore, we sought to determine whether carotid lesions differ between 20 Chinese and 20 Caucasian Americans by MRI. Methods and Results - Inclusion criteria were > 50% stenosis as measured by duplex ultrasound and recent symptoms attributed to carotid artery disease. The patients were imaged in 2 centers ( Beijing, China and Seattle, Wash) using a standardized protocol. Both carotid arteries were reviewed quantitatively ( lumen, wall, outer wall, tissue components) and morphologically ( lesion types, fibrous cap status). Significant differences between the Chinese and Americans were found for the mean size of the lipid/necrotic core (13.6 versus 7.8 mm(2); P = 0.002), percentage of slices with calcified type VII lesions (1.6 versus 12.4%; P = 0.03), and percentage of slices with early type III lesions (19.3 versus 9.3%; P = 0.02). Furthermore, the mean outer wall area in the common carotid artery was larger in the Chinese population ( P = 0.007). Conclusions - This pilot study suggests that composition and morphology of atherosclerotic lesions in symptomatic carotid disease differ between ethno-racial groups. Quantitative MRI-based review of carotid atherosclerosis comparing plaque morphology and composition between ethno-racial groups is feasible, and future MRI studies may improve our understanding of the pathophysiology of this disease. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Peoples Liberat Army Gen Hosp, Dept Radiol, Beijing, Peoples R China. Mt Whisper Light Stat Consulting, Seattle, WA USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Yuan, C (reprint author), Univ Washington, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM cyuan@u.washington.edu FU NHLBI NIH HHS [R01HL61851, R01HL56874] NR 24 TC 25 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2005 VL 25 IS 3 BP 611 EP 616 DI 10.1161/01.ATV.0000155965.54679.79 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 900NL UT WOS:000227221500025 PM 15653565 ER PT J AU Hill, CL Seo, GS Gale, D Totterman, S Gale, ME Felson, DT AF Hill, Catherine L. Seo, Gwy Suk Gale, Daniel Totterman, Saara Gale, M. Elon Felson, David T. TI Cruciate Ligament Integrity in Osteoarthritis of the Knee SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ASSOCIATION; TEARS; PAIN; INSUFFICIENCY; ARTHRITIS; MENISCUS; FEATURES; RUPTURE; JOINT AB Objective. To evaluate, using magnetic resonance imaging (MRI), the prevalence of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) rupture in knees with symptomatic osteoarthritis (OA) compared with those without OA, and the relationship to pain and recalled injury. Methods. MRI and plain radiography of the knee were performed in a group of 360 subjects with painful knee OA (cases; 66.7% male, mean age 67.1 years) and 73 without knee pain (controls; 57.5% male, mean age 66.1 years). MRIs were read for the presence or absence of complete or partial ACL or PCL tear. Subjects with knee pain were asked to quantify severity of pain on a visual analog scale and to report whether they could recall a significant knee injury (requiring use of a cane or crutches). We compared the prevalence of ACL and PCL rupture in those with and those without knee pain and also evaluated whether, in cases, there was any association with recalled knee injury. Results. The proportion of cases who had complete ACL rupture was 22.8%, compared with 2.7% of controls (P = 0.0004). PCL rupture was rare both in cases (0.6%) and in controls (0%). Cases with ACL rupture had more severe radiologic OA (P < 0.0001) and were more likely to have medial joint space narrowing (P < 0.0001) than cases with intact ACLs, but did not have higher pain scores. Among cases, only 47.9% of those with complete ACL tears reported a previous knee injury, compared with 25.9% of those without complete ACL tears (P = 0.003). Conclusion. ACL rupture is more common among those with symptomatic knee OA compared with those without knee OA. Fewer than half of subjects with ACL rupture recall a knee injury, suggesting that this risk factor for knee OA is underrecognized. C1 [Felson, David T.] Boston Med Ctr, Boston, MA USA. [Felson, David T.] Boston Univ, Arthrit Ctr, Boston, MA 02215 USA. [Seo, Gwy Suk; Totterman, Saara] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Gale, Daniel; Gale, M. Elon] Boston VA Healthcare Syst, Boston, MA USA. RP Hill, CL (reprint author), Queen Elizabeth Hosp, Dept Rheumatol, Woodville Rd, Woodville, SA 5011, Australia. EM Catherine.Hill@nwahs.sa.gov.au OI Felson, David/0000-0002-2668-2447 FU NIH [AR-47785]; Arthritis Foundation; Bayer Corporation FX Supported by the NIH (grant AR-47785), the Arthritis Foundation, and the Bayer Corporation. NR 29 TC 73 Z9 77 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 2005 VL 52 IS 3 BP 794 EP 799 DI 10.1002/art.20943 PG 6 WC Rheumatology SC Rheumatology GA 905LU UT WOS:000227570600016 PM 15751064 ER PT J AU Becker, MA Schumacher, HR Wortmann, RL MacDonald, PA Palo, WA Eustace, D Vernillet, L Joseph-Ridge, N AF Becker, Michael A. Schumacher, H. Ralph, Jr. Wortmann, Robert L. MacDonald, Patricia A. Palo, William A. Eustace, Denise Vernillet, Laurent Joseph-Ridge, Nancy TI Febuxostat, a Novel Nonpurine Selective Inhibitor of Xanthine Oxidase SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ALLOPURINOL HYPERSENSITIVITY SYNDROME; CHRONIC GOUT; HYPERURICEMIA; TEI-6720; THERAPY; ATTACKS; METABOLISM; MANAGEMENT; REDUCTION; MECHANISM AB Objective. Gout affects similar to 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>= 8.0 mg/dl). Methods. We conducted a phase 11, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28. Results. Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level < 6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups. Conclusion. Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated. C1 [Becker, Michael A.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Schumacher, H. Ralph, Jr.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Wortmann, Robert L.] Univ Oklahoma, Tulsa, OK USA. [MacDonald, Patricia A.; Palo, William A.; Eustace, Denise; Vernillet, Laurent; Joseph-Ridge, Nancy] TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Becker, MA (reprint author), 5841 S Maryland Ave,MC0930, Chicago, IL 60637 USA. EM mbecker@medicine.bsd.uchicago.edu NR 42 TC 129 Z9 142 U1 4 U2 15 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 2005 VL 52 IS 3 BP 916 EP 923 DI 10.1002/art.20935 PG 8 WC Rheumatology SC Rheumatology GA 905LU UT WOS:000227570600031 PM 15751090 ER PT J AU Warner, JJP Tetreault, P Lehtinen, J Zurakowski, D AF Warner, JJP Tetreault, P Lehtinen, J Zurakowski, D TI Arthroscopic versus mini-open rotator cuff repair: A cohort comparison study SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE arthroscopic rotator cuff repair; mini-open rotator cuff repair; cohort analysis ID FULL-THICKNESS TEARS; SUTURE AB Purpose: To critically compare arthroscopic and mini-open rotator cuff repair. Type of Study: Retrospective case control study. Methods: Nine patients who had an arthroscopic rotator cuff repair (ARCR) were matched for age, gender, dominance, side of injury, history of trauma, duration of symptoms, and type of rotator cuff injury, with 12 patients who had a mini-open rotator cuff repair (MOR). Comparison included a preoperative and postoperative physical examination as well as a completed Simple Shoulder Test (SST) questionnaire at the latest follow-up at a minimum of 27 months. Results: Both groups had significant reductions in pain scores (P < .01) and there was no significant difference in preoperative or postoperative active flexion or external rotation between both groups (P > .20). Although the ARCR group showed a significant improvement in strength (P < .01) and the MOR group did not, no patient had less than 4/5 strength. The impingement sign remained positive in I MOR patient, but all patients had a negative Jobe's test result. Pain and Tasks assessment by SST questionnaire showed that neither group had night pain or discomfort when using their arms overhead. There were no significant differences in the overall SST scores between groups. Conclusions: Because all patients in each group were satisfied with the procedure and there were no objective differences in outcome, we conclude that there is no difference in outcome between ARCR and MOR. Thus, the choice of one approach over the other is best based on surgeon or patient preference. Level of Evidence: Level III, Retrospective Case Control Study. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Shoulder Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Hop Notre Dame de Bon Secours, Dept Orthopaed Surg, Montreal, PQ H2L 4K8, Canada. Univ Montreal, Montreal, PQ, Canada. RP Warner, JJP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Shoulder Serv,Dept Orthopaed Surg, 275 Cambridge St, Boston, MA 02114 USA. EM jwarner@partners.org NR 17 TC 67 Z9 71 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD MAR PY 2005 VL 21 IS 3 BP 328 EP 332 DI 10.1016/j.arthro.2004.11.006 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 906MG UT WOS:000227645700013 PM 15756188 ER PT J AU Gottrup, C Thomsen, K Locht, P Wu, O Sorensen, AG Koroshetz, WJ Ostergaard, L AF Gottrup, C Thomsen, K Locht, P Wu, O Sorensen, AG Koroshetz, WJ Ostergaard, L TI Applying instance-based techniques to prediction of final outcome in acute stroke SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE k-nearest neighbor; acute cerebral stroke; magnetic resonance imaging; decision support systems ID ACUTE CEREBRAL-ISCHEMIA; LEARNING ALGORITHMS; ROC CURVE; DIFFUSION; IMAGES; BRAIN; MODEL; AREA AB Objective : Acute cerebral stroke is a frequent cause of death and the major cause of adult neurological disability in the western world. Thrombolysis is the only established treatment of ischemic stroke; however, its use carries a substantial risk of symptomatic intracerebral hemorrhage. A clinical tool. to guide the use of thrombolysis would be very valuable. One of the major goals of such a tool would be the identification of potentially salvageable tissue. This requires an accurate prediction of the extent of infarction if untreated. In this study, we investigate the applicability of highly flexible instance-based (IB) methods for such predictions. Methods and materials : Based on information obtained from magnetic resonance imaging of 14 patients with acute stroke, we explored three different implementations of the IB method: k-NN, Gaussian weighted, and constant radius search classification. Receiver operating characteristics analysis, in particular area under the curve (AUC), was used as performance measure. Results We found no significant difference (P = 0.48) in performance for the optimal k-NN (k = 164, AUC = 0.814 +/- 0.001) and Gaussian weight (sigma = 0.17, AUC = 0.813 +/- 0.001) implementations, while they were both significantly better (P < 1 x 10(-6) for both) than the constant radius implementation (R = 0.28, AUC = 0.809 +/- 0.001). Qualitative analyses of the distribution of instances in the feature space indicated that non-infarcted instances tends to cluster together while infarcted instances are more dispersed, and that there may not exist a stringent boundary separating infarcted from non-infarcted instances. Conclusions : This study shows that IB methods can be used, and may be advantageous, for predicting final infarct in patients with acute stroke, but further work must be done to make them clinically applicable. (c) 2004 Elsevier B.V. All rights reserved. C1 DIMAC AS, Hojbjerg, Denmark. Aarhus Univ Hosp, Dept Neuroradiol, Ctr Funct Integrat Neurosci, DK-8000 Aarhus, Denmark. Athinoula A Martinos Ctr Biomed Imaging, MGH, MIT, HMS, Charlestown, MA USA. Univ Utrecht, Ctr Med, Image Sci Inst, Utrecht, Netherlands. Massachusetts Gen Hosp, Dept Neurol, Stroke Unit, Boston, MA 02114 USA. RP Gottrup, C (reprint author), DIMAC AS, Hojbjerg, Denmark. EM cgottrup@pet.auh.dk RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 FU NINDS NIH HHS [5 R01 NS 38477] NR 25 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD MAR PY 2005 VL 33 IS 3 BP 223 EP 236 DI 10.1016/j.artmed.2004.06.003 PG 14 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 920FD UT WOS:000228673900003 PM 15811787 ER PT J AU Salinsky, MC Storzbach, D AF Salinsky, MC Storzbach, D TI The Portland neurotoxicity scale - Validation of a brief self-report measure of antiepileptic-drug-related neurotoxicity SO ASSESSMENT LA English DT Article DE antiepileptic drugs; cognition; neurotoxicity; self-reporting ID ASSESSMENT SCHEDULE ABNAS; TONIC-CLONIC SEIZURES; PATIENT-BASED SCALE; QUALITY-OF-LIFE; NEUROPSYCHOLOGICAL ASSESSMENT; DOUBLE-BLIND; COGNITIVE PERFORMANCE; HEALTHY-VOLUNTEERS; EPILEPSY; CARBAMAZEPINE AB The Portland Neurotoxicity Scale (PNS) is a brief patient-based survey of neurotoxicity complaints commonly encountered with the use of antiepileptic drugs (AEDs). The authors present data on the validity of this scale, particularly when used in longitudinal studies. Participants included 55 healthy controls, 23 epilepsy patient controls, and 86 healthy volunteers who took various AEDs or placebos for 12 weeks as part of randomized, double-blind studies of AED effects on cognitive abilities. Test-retest reliability in the control groups averaged .80 (total score). Test-retest changes in the PNS were sensitive to AED usage in general (p < .001) and to each of the five AEDs tested but not to placebo. Test-retest changes in the PNS were strongly correlated with several scales of the Profile of Mood States but only weakly correlated with objective cognitive test measures. The PNS has satisfactory psychometric properties and is sensitive to AED usage in test-retest studies. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Salinsky, MC (reprint author), Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 35 TC 10 Z9 10 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD MAR PY 2005 VL 12 IS 1 BP 107 EP 117 DI 10.1177/1073191104272857 PG 11 WC Psychology, Clinical SC Psychology GA 901MM UT WOS:000227286600011 PM 15695749 ER PT J AU Oshima, M Ohtani, M Deitiker, PR Smith, RG Mosier, DR Atassi, MZ AF Oshima, M Ohtani, M Deitiker, PR Smith, RG Mosier, DR Atassi, MZ TI Suppression by mAbs against DQB1 peptides of in vitro proliferation of AChR-specific T cells from myasthenia gravis patients SO AUTOIMMUNITY LA English DT Article DE acetylcholine receptor; antigen-presenting region; MHC; monoclonal antibodies; myasthenia gravis ID HUMAN ACETYLCHOLINE-RECEPTOR; PERIPHERAL-BLOOD LYMPHOCYTES; MHC CLASS-II; ALPHA-SUBUNIT; BETA-CHAIN; EXTRACELLULAR PART; HLA-DR; ANTIBODY; REGION; BINDING AB It has been indicated that multiple genes, including HLA genes, are collectively involved in the susceptibility to myasthenia gravis (MG). DQB1 alleles represent one of those associated with MG. We have prepared B-cell hybridomas that produce mAbs against peptides corresponding to the tip of the MHC antigen-binding cavity (region 70-90) of alleles DQB1*02, *03, *05 and *06. The mAbs bound to DQ molecules isolated from cells. In the assays using peripheral blood lymphocytes (PBL) from patients with MG, the mAbs against peptides of the correlate HLA DQ sequences inhibited the in vitro proliferation of acetylcholine receptor (AChR)-specific T cells. The results indicate that the function of disease-related MHC alleles may be blocked by directly and selectively targeting the antigen-presenting region on these MHC molecules. The results also suggest that DQ molecules are one of those involved in the restriction of autoimmune anti-AChR responses in MG. The strategy could provide an effective means for immunointervention in MG. It may also potentially be adapted for down-regulation of undesirable immune responses such as in other autoimmune diseases, allergic reactions, or clinical conditions where immune responses to a therapeutic protein develop. C1 Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Univ Texas, Med Branch, Dept Neurol, Galveston, TX 77555 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. ME DeBakey VA Med Ctr, Neurol Serv, Houston, TX 77030 USA. ME DeBakey VA Med Ctr, Med Res Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RP Oshima, M (reprint author), Baylor Coll Med, Dept Biochem & Mol Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM moshima@bcm.tmc.edu NR 45 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD MAR PY 2005 VL 38 IS 2 BP 161 EP 169 DI 10.1080/08916930500050491 PG 9 WC Immunology SC Immunology GA 939YO UT WOS:000230109000008 PM 16040337 ER PT J AU Yamashita, Y Chiba, Y Xia, C Hirayoshi, K Satoh, M Saitoh, Y Shimada, A Nakamura, E Hosokawa, M AF Yamashita, Y Chiba, Y Xia, C Hirayoshi, K Satoh, M Saitoh, Y Shimada, A Nakamura, E Hosokawa, M TI Different adaptive traits to cold exposure in young senescence-accelerated mice SO BIOGERONTOLOGY LA English DT Article DE body temperature; cold exposure; senescence-accelerated mouse (SAM); spontaneous motor activity (SMA); uncoupling protein 1 (UCP1) ID BROWN ADIPOSE-TISSUE; UNCOUPLING PROTEIN; NONSHIVERING THERMOGENESIS; THERMOREGULATION; MODEL; RATS AB A reduced adaptation to cold is a prominent feature in aged mammals, including humans. The accelerated senescence-prone strain of mice (SAMP) has been studied as an animal model for several age-associated disorders and in the acceleration of senescence. Recent studies revealed that SAMP strains have dysfunctional hyperactive mitochondria and are under a higher oxidative stress status from a young age. To investigate whether young SAMP mice show impaired cold adaptation abilities, we performed cold-exposure experiments. There were no strain differences in baseline body temperature and lowest reached temperature during cold exposure. SAMP1 mice took longer times to reach their lowest temperature in comparison to SAMR1 mice. SAMR1 mice showed an elevation in temperature following cold exposure, whereas SAMP1 mice did not. Behavioral observations demonstrated that SAMP1 mice moved more actively than SAMR1 during cold exposure. However, mRNA levels of uncoupling protein 1 (UCP1), a heat generating protein, as well as plasma norepinephrine levels, were higher in SAMP1 than in SAMR1 mice. This newly found physiological phenotype in SAMP1 mice provides us with a tool to clarify the genetic mechanism which accelerates the senescence process and helps us develop medical means which will bring mankind to a healthy old age. C1 Aichi Human Serv Ctr, Inst Dev Res, Dept Pathol, Aichi 4800392, Japan. Kyoto Univ, Grad Sch Human & Environm Studies, Lab Aging Study, Sakyo Ku, Kyoto 6068507, Japan. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. Kyoto Univ, Inst Frontier Med Sci, Dept Ultrastruct Res, Sakyo Ku, Kyoto 6068507, Japan. RP Chiba, Y (reprint author), Aichi Human Serv Ctr, Inst Dev Res, Dept Pathol, Aichi 4800392, Japan. EM ychiba@inst-hsc.jp NR 17 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1389-5729 J9 BIOGERONTOLOGY JI Biogerontology PD MAR PY 2005 VL 6 IS 2 BP 133 EP 139 DI 10.1007/s10522-005-3499-x PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 948GX UT WOS:000230705200005 PM 16034680 ER PT J AU Valera, EM Faraone, SV Biederman, J Poldrack, RA Seidman, LJ AF Valera, EM Faraone, SV Biederman, J Poldrack, RA Seidman, LJ TI Functional neuroanatomy of working memory in adults with attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; fMRI; working memory; cerebellum; n-back; prefrontal cortex ID DEFICIT-HYPERACTIVITY DISORDER; QUANTITATIVE MORPHOLOGY; LEARNING-DISABILITIES; CORPUS-CALLOSUM; CHILDHOOD-ONSET; BASAL GANGLIA; CEREBELLAR; CHILDREN; DYSFUNCTION; CORTEX AB Background: Attention-deficit/hyperactivity disorder (ADHD) in adults is an increasingly recognized psychiatric disorder, linked with impairments in numerous life domains and with neurocognitive dysfunctions. However, the neural substrate of cognitive functioning in adults with this disorder has been relatively unexamined. The objective of this study was to examine neural functioning in ADHD adults during performance on a verbal working memory task. Methods. A sample of unmedicated adults with ADHD (n = 20) and control subjects (n = 20) performed a 2-back task of working memory, and the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) response was used as a measure of neural activity during working memory performance. Results. Though working memory performance did not differ significantly between ADHD adults and control subjects, ADHD adults showed significantly decreased activity in cerebellar and occipital regions and a trend toward decreased activation in an a priori predicted region of the prefrontal cortex. Conclusions: ADHD adults showed altered patterns of neural activity despite comparable performance on a verbal working memory task. These findings suggest that the cerebellum is involved in the pathophysiology of at least some cognitive deficits associated with ADHD and emphasize the need for additional research aimed at elucidating the role of the cerebellum in ADHD symptomatology. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Valera, EM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Room 2651,149 13th St, Charlestown, MA 02129 USA. EM eve_valera@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [1 F32 MH065040-01A1, MH 57934, MH62152-02] NR 65 TC 122 Z9 129 U1 4 U2 16 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 MAR 1 PY 2005 VL 57 IS 5 BP 439 EP 447 DI 10.1016/j.biopsych.2004.11.034 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 903HB UT WOS:000227415400001 PM 15737657 ER PT J AU Spencer, T Biederman, J Wilens, T Doyle, R Surman, C Prince, J Mick, E Aleardi, M Herzig, K Faraone, S AF Spencer, T Biederman, J Wilens, T Doyle, R Surman, C Prince, J Mick, E Aleardi, M Herzig, K Faraone, S TI A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHID; adult; methylphenidate; psychopharmacology; randomized trial; stimulant ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; LONGITUDINAL DATA; RISK-FACTORS; SAMPLE; AMPHETAMINE; DEPRESSION; CHILDREN; EFFICACY; DENSITY AB Background: The few controlled studies of methylphenidate (MPH) in adults with attention deficit/hyperactivity disorder (ADHD) have reported equivocal results. A previous, pilot study by our group suggested that these results were dure to inadequate dosing. Method: We conducted a randomized, 6-week, placebo-controlled, parallel study of MPH in 146 adult patients with DSM-IV ADHD using standardized instruments for diagnosis, separate assessments of ADHD, depressive and anxiety symptoms, and a robust average oral daily doze of 1.1 mg/kg/day. Results: We found a marked therapeutic response for the MPH treatment of ADHD symptoms that exceeded the placebo response (76% vs. 19%). Treatment was safe and well tolerated. Response to MPH was independent of socioeconomic status, gender, and lifetime history of psychiatric comorbidity. Conclusions: These results confirm that robust doses of MPH are effective in the treatment of adult ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC725, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Ins Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC725, Psychiat Serv, 15 Parkman St, Boston, MA 02114 USA. EM tspencer@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R29MH57511] NR 55 TC 195 Z9 199 U1 2 U2 17 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 MAR 1 PY 2005 VL 57 IS 5 BP 456 EP 463 DI 10.1016/j.biopsych.2004.11.043 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 903HB UT WOS:000227415400003 PM 15737659 ER PT J AU Bartzokis, G Lu, PH Turner, J Mintz, J Saunders, CS AF Bartzokis, G Lu, PH Turner, J Mintz, J Saunders, CS TI Adjunctive risperidone in the treatment of chronic combat-related posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 58th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CA SP Soc Biol Psychiat DE PTSD; posttraumatic stress disorder; risperidone; antipsychotic; atypical; combat; chronic ID DOUBLE-BLIND; RATING-SCALE; PLACEBO; SCHIZOPHRENIA; OLANZAPINE; DEPRESSION; SERTRALINE; CLOZAPINE; SYMPTOMS; CHILDREN AB Background: The efficacy and safety of risperidone was evaluated in veteran patients with chronic combat-related postraumatic stress disorder (PTSD) who were referred to a residential treatment program. Methods. Seventy-three subjects volunteered to participate in this double-blind. placebo-controlled study, which comprised of a 5 week residential program followed by a 3-month outpatient follow-up. Risperidone was added to a stable psychotropic medication regimen in 92% of subjects. Primary outcome measures were the Clinician-Administered PTSD scale (CAPS-total) and its three subscales; B (Re-experiencing), C(Avoidance) and D (Arousal). Secondary outcome measures were the Hamilton Anxiety (HAM-A) and Depression (HAM-D) scales, and the Positive and Negative Syndrome Scale, Positive Subscale (PANSS-P). Results: Sixty-five subjects were randomized and 48 completed the 4-month study. Significantly greater improvement in symptoms was observed in subjects receiving risperidone compared to placebo on the CAPS-total and CAPS-D subscale scores and also on HAM-A and PANSS-P. Numerically greater improvements in all the remaining measures were noted with risperidone, but the differences did not reach statistical significance. Risperidone was well tolerated. Conclusions. These results suggest that adjunctive risperidone improved a broad range of pychiatric symptoms in patients with chronic combat-related PTSD. The data support the concept that a typical antipsychotic medications may have a wider therapeutic spectrum that goes beyond the treatment of psychosis. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Bartzokis, G (reprint author), Reed Neurol Res Ctr, 710 Westwood Pl,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 NR 31 TC 108 Z9 111 U1 1 U2 15 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 MAR 1 PY 2005 VL 57 IS 5 BP 474 EP 479 DI 10.1016/j.biopsych.2004.11.039 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 903HB UT WOS:000227415400005 PM 15737661 ER PT J AU Shaughnessy, PJ Bachier, C Grimley, M Freytes, CO Callander, NS Essell, YH Flomenberg, N Selby, G Lemaistre, CE AF Shaughnessy, PJ Bachier, C Grimley, M Freytes, CO Callander, NS Essell, YH Flomenberg, N Selby, G Lemaistre, CE TI Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE denileukin diftitox; steroid resistance; graft-versus-host disease ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; INTERLEUKIN-2 RECEPTOR; RETROSPECTIVE ANALYSIS; PHASE-II; T-CELLS; ANTIBODY; THERAPY; TRIAL; DAB(389)IL-2 AB Acute graft-versus-host disease (aGVHD) is partly mediated through activated T cells, and these cells are known to express the high-affinity receptor for interleukin 2 (IL-2R). Denileukin diftitox is composed of human IL-2 and diphtheria toxin that is cytotoxic to activated lymphocytes expressing the high-affinity IL-2R. We describe the results of a phase H study of denileukin diftitox in 22 patients with steroid-resistant aGVHD. Twenty patients were treated at dose level 1 (4.5 mu g/kg daily on days 1-5 and then weekly on study days 8, 15, 22, and 29), and 2 patients were treated at dose level 2 (9.0 mu g/kg delivered on the same schedule). Dose level 2 was associated with grade 3/4 renal and hepatic toxicity and vascular leak syndrome, and no further patients were treated at this level. Dose level I was generally well tolerated. The response of aGVHD was assessed at study days 36 and 100. Nine patients (41%) responded, all with a complete response at study day 36, and 6 patients (27%) responded at study day 100 (4 complete responses and 2 partial responses). Denileukin diftitox has promising activity in steroid-resistant aGVHD, and further study is warranted. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Texas Transplant Inst, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Jewish Hosp, Cincinnati, OH USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Univ Oklahoma, Oklahoma City, OK USA. RP Shaughnessy, PJ (reprint author), Texas Transplant Inst, 8201 Ewing Halsell,Ste 280, San Antonio, TX 78229 USA. EM Paul.Shaughnessy@MHShealth.com NR 31 TC 42 Z9 47 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2005 VL 11 IS 3 BP 188 EP 193 DI 10.1016/j.bbmt.2004.11.022 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 910US UT WOS:000227958300004 PM 15744237 ER PT J AU Antin, JH Guinan, EC Avigan, D Soiffer, RJ Joyce, RM Martin, VJ Molrine, DC AF Antin, JH Guinan, EC Avigan, D Soiffer, RJ Joyce, RM Martin, VJ Molrine, DC TI Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE hematopoietic cell transplantation; pneumococcal conjugate vaccine; immunization; autologous ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; VERSUS-HOST-DISEASE; B CONJUGATE; DONOR IMMUNIZATION; RECIPIENTS; CHILDREN; IMMUNOGENICITY; POLYSACCHARIDE; INFECTIONS AB Patients undergoing autologous hematopoietic stem cell transplantation (autoHCT) are at increased risk for infection with Streptococcus pneumoniae and have impaired antibody responses to pneumococcal polysaccharide vaccines. We performed this study to examine the ability of autoHCT patients to respond to a heptavalent pneumococcal conjugate vaccine (PCV7) given after transplantation and to determine whether there was a potential benefit of immunizing these patients before stem cell collection. Sixty-one patients scheduled for autoHCT were randomized to receive either PCV7 or no vaccine before stem cell collection. After stem cell reinfusion, all study patients were immunized with PCV7 at 3, 6, and 12 months. Pneumococcal immunoglobulin G antibody concentrations were measured at the time of each immunization and 1 month after the 12-month dose. Serotype-specific pneumococcal antibody concentrations were significantly higher in patients immunized with PCV7 before stem cell collection compared with patients not immunized before their stem cells were collected for 6 of 7 serotypes at 3 months, 6 of 7 serotypes at 6 months, 4 of 7 serotypes at 12 months, and 3 of 7 serotypes at 13 months. After the 3-dose series of PCV7 after autoHCT, > 60% of study patients had protective concentrations of antibody to all 7 vaccine serotypes regardless of immunization before stem cell collection. Pneumococcal conjugate vaccine is immunogenic in autoHCT patients and may be an effective strategy to prevent invasive disease after transplantation. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Univ Massachusetts, Massachusetts Biol Labs, Sch Med, Jamaica Plain, MA 02130 USA. Dana Farber Canc Inst, Dept Adult Oncol & Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Hematol Malignancy Bone Marrow Transplant Program, Boston, MA 02215 USA. RP Molrine, DC (reprint author), Univ Massachusetts, Massachusetts Biol Labs, Sch Med, 305 South St, Jamaica Plain, MA 02130 USA. EM deborah.molrine@umassmed.edu NR 37 TC 29 Z9 30 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2005 VL 11 IS 3 BP 213 EP 222 DI 10.1016/j.bbmt.2004.12.330 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 910US UT WOS:000227958300007 PM 15744240 ER PT J AU Mielcarek, M Gooley, T Martin, P Chauncey, TR Young, BA Storb, R Torok-Storb, B AF Mielcarek, M Gooley, T Martin, P Chauncey, TR Young, BA Storb, R Torok-Storb, B TI Effects of race on survival after stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE hematopoietic stem cell transplantation; race; mortality; graft-versus-host disease; relapse; socioeconomic factors ID VERSUS-HOST-DISEASE; ALLOGENEIC MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; ACUTE GRAFT; SOCIOECONOMIC-STATUS; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; DONOR PROGRAM; PROPHYLAXIS; GENE AB Effects of race or ethnicity on survival after high-dose chemoradiation followed by stem cell transplantation (SCT) have not been thoroughly evaluated. We analyzed survival according to racial/ethnic categories for 3587 consecutive patients who had SCT at a single US institution between July 1992 and December 2000. Among 1366 patients who received autologous SCT, race or ethnicity was not significantly associated with survival. In contrast, among 2221 patients who received allogeneic SCT from IIIA-matched unrelated or sibling donors, blacks had a significantly greater mortality than whites (unadjusted hazard ratio, 1.65; 95% confidence interval, 1.21-2.25). Mortality among other racial or ethnic groups was not significantly different from that among whites. The greater mortality hazard among blacks persisted after controlling for donor type, pretransplantation risk category, patient age, donor/patient sex, and cytomegalovirus exposure (hazard ratio, 1.71; 95% confidence interval, 1.25-2.34). SCT from both HLA-matched unrelated and IRA-identical sibling donors was associated with more severe acute graft-versus-host disease and higher nonrelapse mortality among blacks compared with whites. Furthermore, blacks who received SCT for chronic myeloid leukemia had longer diagnosis-to-transplantation intervals than whites. A matched-cohort analysis showed that the higher mortality among blacks could not be explained by obvious socioeconomic differences. The higher incidence of severe graft-versus-host disease among blacks compared with whites, both with PILA-identical sibling donors, might be related to yet-unidentified "immune-enhancing" genetic polymorphisms. We cannot exclude the possibility that the increased mortality risk among blacks after discharge from the transplant center might in part be related to unidentified sociocultural differences that influence medical care. 2005 American Society for Blood and Marrow Transplantation. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Mielcarek, M (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D1-100, Seattle, WA 98109 USA. EM mmielcar@fhcrc.org NR 38 TC 23 Z9 23 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2005 VL 11 IS 3 BP 231 EP 239 DI 10.1016/j.bbmt.2004.12.327 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 910US UT WOS:000227958300009 PM 15744242 ER PT J AU Huang, J Harrington, D AF Huang, J Harrington, D TI Iterative partial least squares with right-censored data analysis: A comparison to other dimension reduction techniques SO BIOMETRICS LA English DT Article DE accelerated failure time model; Buckley-James estimation; cross-validation; partial least squares; prediction; synthetic data ID PRINCIPAL COMPONENTS REGRESSION; LINEAR-REGRESSION; MODELS; PLS AB In the linear model with right-censored responses and many potential explanatory variables, regression parameter estimates may be unstable or, when the covariates outnumber the uncensored observations, not estimable. We propose an iterative algorithm for partial least squares, based on the Buckley-James estimating equation, to estimate the covariate effect and predict the response for a future subject with a given set of covariates. We use a leave-two-out cross-validation method for empirically selecting the number of components in the partial least-squares fit that approximately minimizes the error in estimating the covariate effect of a future observation. Simulation studies compare the methods discussed here with other dimension reduction techniques. Data from the AIDS Clinical Trials Group protocol 333 are used to motivate the methodology. C1 Brigham & Womens Hosp, Sect Clin Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Huang, J (reprint author), Brigham & Womens Hosp, Sect Clin Sci, 221 Longwood Ave, Boston, MA 02115 USA. EM jjhuang@post.harvard.edu FU NCI NIH HHS [CA39929]; NIAID NIH HHS [AI58217, AI24643] NR 19 TC 10 Z9 11 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2005 VL 61 IS 1 BP 17 EP 24 DI 10.1111/j.0006-341X.2005.040304.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 905NX UT WOS:000227576600003 PM 15737074 ER PT J AU Hayden, D Pauler, DK Schoenfeld, D AF Hayden, D Pauler, DK Schoenfeld, D TI An estimator for treatment comparisons among survivors in randomized trials SO BIOMETRICS LA English DT Article DE counterfactual; explainable nonrandom survival; survivor average causal effect ID NONCOMPLIANCE; DURATION AB In clinical trials of advanced-stage disease it is often of interest to perform treatment comparisons for endpoints which are defined only for survivors. Examples include time on ventilation in ventilation studies, change in quality of life in health-related quality-of-life studies, and duration of response to therapy in therapeutic trials. Randomized treatment comparisons for these endpoints cannot be performed because the outcomes are only defined in the nonrandomly selected subgroup of survivors. We propose a new evaluation of the survivor average causal effect (SACE) for treatment comparisons of this nature. We provide an estimator of SACE in the presence of no unmeasured confounders, a nontestable assumption, which identifies SACE. We also outline a sensitivity analysis for exploring robustness of conclusions to deviations from this assumption. We apply this method to duration of ventilation in a clinical trial of acute respiratory distress syndrome. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hayden, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dschoenfeld@partners.org FU NCI NIH HHS [CA 74302]; NHLBI NIH HHS [NHLBI-HR-46064] NR 13 TC 35 Z9 35 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2005 VL 61 IS 1 BP 305 EP 310 DI 10.1111/j.0006-341X.2005.030227.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 905NX UT WOS:000227576600036 PM 15737107 ER PT J AU Sun, CH Munn, LL AF Sun, CH Munn, LL TI Particulate nature of blood determines macroscopic rheology: A 2-D lattice Boltzmann analysis SO BIOPHYSICAL JOURNAL LA English DT Article ID MULTIPARTICLE ADHESIVE DYNAMICS; SHEAR-FLOW; CELL-ADHESION; NARROW TUBES; LEUKOCYTES; SUSPENSIONS; EQUATION; MODEL; MICROCIRCULATION; ERYTHROCYTES AB Historically, predicting macroscopic blood flow characteristics such as viscosity has been an empirical process due to the difficulty in rigorously including the particulate nature of blood in a mathematical representation of blood rheology. Using a two-dimensional lattice Boltzmann approach, we have simulated the flow of red blood cells in a blood vessel to estimate flow resistance at various hematocrits and vessel diameters. By including white blood cells ( WBCs) in the flow, we also calculate the increase in resistance due to white cell rolling and adhesion. The model considers the blood as a suspension of particles in plasma, accounting for cell-cell and cell-wall interactions to predict macroscopic blood rheology. The model is able to reproduce the Fahraeus- Lindqvist effect, i.e., the increase in relative apparent viscosity as tube size increases, and the Fahraeus effect, i.e., tube hematocrit is lower than discharge hematocrit. In addition, the model allows direct assessment of the effect of WBCs on blood flow in the microvasculature, reproducing the dramatic increases in flow resistance as WBCs enter short capillary segments. This powerful and flexible model can be used to predict blood flow properties in any vessel geometry and with any blood composition. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NHLBI NIH HHS [R01 HL064240-03, R01 HL064240-07, HL64240, R01 HL064240-04, R01 HL064240-08, R01 HL064240-05, R01 HL064240-06, R01 HL064240, R01 HL064240-01, R01 HL064240-02] NR 36 TC 61 Z9 62 U1 1 U2 12 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2005 VL 88 IS 3 BP 1635 EP 1645 DI 10.1529/biophysj.104.051151 PG 11 WC Biophysics SC Biophysics GA 904JV UT WOS:000227494600015 PM 15613630 ER PT J AU Monti, S Savage, KJ Kutok, JL Feuerhake, F Kurtin, P Mihm, M Wu, BY Pasqualucci, L Neuberg, D Aguiar, RCT Dal Cin, P Ladd, C Pinkus, GS Salles, G Harris, NL Dalla-Favera, R Habermann, TM Aster, JC Golub, TR Shipp, MA AF Monti, S Savage, KJ Kutok, JL Feuerhake, F Kurtin, P Mihm, M Wu, BY Pasqualucci, L Neuberg, D Aguiar, RCT Dal Cin, P Ladd, C Pinkus, GS Salles, G Harris, NL Dalla-Favera, R Habermann, TM Aster, JC Golub, TR Shipp, MA TI Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response SO BLOOD LA English DT Article ID LYSOSOMAL THIOL REDUCTASE; T-CELL; GENE-EXPRESSION; HODGKIN LYMPHOMA; ANTIGEN PRESENTATION; RECEPTOR; FAMILY; CHEMOTHERAPY; ACTIVATION; APOPTOSIS AB Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognized variability in clinical outcome, genetic features, and cells of origin. To date, transcriptional profiling has been used to highlight similarities between DLBCL tumor cells and normal B-cell subtypes and associate genes and pathways with unfavorable outcome. To identify robust and highly reproducible DLBCL subtypes with comprehensive transcriptional signatures, we used a large series of newly diagnosed DLBCLs, whole genome arrays, and multiple clustering methods. Tumors were also analyzed for known common genetic abnormalities in DLBCL. There were 3 discrete subsets of DLBCL-"oxidative phosphorylation," "B-cell receptor/proliferation," and "host response" (HR-Identified characterized using gene set enrichment analysis and confirmed in an independent series. HR tumors had increased expression of T/natural killer cell receptor and activation pathway components, complement cascade members, macrophageldendritic cell markers, and inflammatory mediators. HR DLB-CLs also contained significantly higher numbers of morphologically distinct CD2(+)/CD3(+) tumor-infiltrating lymphocytes and interdigitating S100(+)/gamma interferon-induced lysosomal transferase-positive (GILT(+)) CD1a(-)/CD123(-) dendritic cells. The HR cluster shared features of histologically defined T-cell/histiocyte-rich B-cell lymphoma, including fewer genetic abnormalities, younger age at presentation, and frequent splenic and bone marrow involvement. These studies identity tumor microenvironment and host inflammatory response as defining features in DLBCL and suggest rational treatment targets in specific DLBCL subsets. C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Broad Inst Cambridge, Cambridge, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Mayo Clin, Dept Pathol, Rochester, MN USA. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Med, Rochester, MN USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Columbia Univ, Inst Canc Genet, New York, NY USA. Ctr Hosp Lyon Sud, Dept Hematol, Lyon, France. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu NR 63 TC 416 Z9 429 U1 1 U2 12 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 MAR 1 PY 2005 VL 105 IS 5 BP 1851 EP 1861 DI 10.1182/blood-2004.07.2947 PG 11 WC Hematology SC Hematology GA 901UU UT WOS:000227308400012 PM 15550490 ER PT J AU Yang, G Huang, SC Wu, JY Benz, EJ AF Yang, G Huang, SC Wu, JY Benz, EJ TI An erythroid differentiation-specific splicing switch in protein 4.1R mediated by the interaction of SF2/ASF with an exonic splicing enhancer SO BLOOD LA English DT Article ID PRE-MESSENGER-RNA; SR PROTEINS; HNRNP A1; IN-VIVO; SILENCER; CELLS; APOPTOSIS; ELEMENTS; ERYTHROPOIESIS; EXPRESSION AB Protein 4.1R is a vital component of the red blood cell membrane cytoskeleton. Promotion of cytoskeletal junctional complex stability requires an erythroid differentiation stage-specific splicing switch promoting inclusion of exon 16 within the spectrin/actin binding domain. We showed earlier that an intricate combination of positive and negative RNA elements controls exon 16 splicing. In this report, we further identified 3 putative exonic splicing enhancers within exon 16 and investigated the function of the sequence CAGACAT in the regulation of exon 16 splicing. Mutation of these sequences leads to increased exclusion of exon 16 in both in vivo and in vitro splicing assays, indicating that CAGACAT is a functional exonic splicing enhancer. UV cross-linking further detects an approximately 33-kDa protein that specifically binds to the CAGACAT-containing transcript. An anti-SF2/ASF antibody specifically immunoprecipitates the approximately 33-kDa protein. Furthermore, SF2/ASF stimulates exon 16 inclusion in both in vitro complementation assays and minigene-transfected mouse erythroleukemia cells (MELCs). Finally, SF2/ASF expression is up-regulated and correlates with exon 16 inclusion in differentiated MELCs. These results suggest that increased splicing factor 2/alternative splicing factor (SF2/ASF) expression in differentiated mouse erythroleukemia mediates a differentiation stage-specific exon 16 splicing switch through its interaction with the exonic splicing enhancer. (C) 2005 by The American Society of Hematology C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Huang, SC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D610,44 Binney St, Boston, MA 02115 USA. EM shu-ching_huang@dfci.harvard.edu FU NHLBI NIH HHS [HL24385] NR 51 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2005 VL 105 IS 5 BP 2146 EP 2153 DI 10.1182/blood-2004-05-1757 PG 8 WC Hematology SC Hematology GA 901UU UT WOS:000227308400054 PM 15522963 ER PT J AU Craiu, A Saito, Y Limon, A Eppich, HM Olson, DP Rodrigues, N Adams, GB Dombkowski, D Richardson, P Schlossman, R Choi, PS Grogins, J O'Connor, PG Cohen, K Attar, EC Freshman, J Rich, R Mangano, JA Gribben, JG Anderson, KC Scadden, DT AF Craiu, A Saito, Y Limon, A Eppich, HM Olson, DP Rodrigues, N Adams, GB Dombkowski, D Richardson, P Schlossman, R Choi, PS Grogins, J O'Connor, PG Cohen, K Attar, EC Freshman, J Rich, R Mangano, JA Gribben, JG Anderson, KC Scadden, DT TI Flowing cells through pulsed electric fields efficiently purges stem cell preparations of contaminating myeloma cells while preserving stem cell function SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MULTIPLE-MYELOMA; HEMATOPOIETIC-CELLS; BREAST-CANCER; THERAPY; RELAPSE; SELECTION; MARKING AB Autologous stem cell transplantation, in the setting of hematologic malignancies such as lymphoma, improves disease-free survival if the graft has undergone tumor purging. Here we show that flowing hematopoietic cells through pulsed electric fields (PEFs) effectively purges myeloma cells without sacrificing functional stem cells. Electric fields can induce irreversible cell membrane pores in direct relation to cell diameter, an effect we exploit in a flowing system appropriate for clinical scale. Multiple myeloma (MM) cell lines admixed with human bone marrow (BM) or peripheral blood (PB) cells were passed through PEFs at 1.35 kV/cm to 1.4 kV/cm, resulting in 3- to 4-log tumor cell depletion by flow cytometry and 4.5- to 6-log depletion by tumor regrowth cultures. Samples from patients with MM gave similar results by cytometry. Stem cell engraftment into nonobese diabetic-severe combined immunodeficient (NOD/SCID)/beta(2)m(-/-) mice was unperturbed by PEFs. Flowing cells through PEFs is a promising technology for rapid tumor cell purging of clinical progenitor cell preparations. (C) 2005 by The American Society of Hematology C1 Sci Res Lab Inc, Somerville, MA USA. Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Regenerat Med & Technol, 149 13th St,Rm 5212D, Hillsborough 02129, North Ireland. EM scadden.david@mgh.harvard.edu FU NCI NIH HHS [R44CA079364-02] NR 21 TC 5 Z9 6 U1 1 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 MAR 1 PY 2005 VL 105 IS 5 BP 2235 EP 2238 DI 10.1182/blood-2003-12-4399 PG 4 WC Hematology SC Hematology GA 901UU UT WOS:000227308400066 PM 15292069 ER PT J AU Moran, TB Cantor, AB AF Moran, TB Cantor, AB TI Identification of a novel zinc finger transcription factor associated with GATA-1 in hematopoietic cells. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 14th Conference on Hemoglobin Switching CY SEP 10-14, 2004 CL Orcas Isl, WA C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Childrens Hosp Boston,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2005 VL 34 IS 2 MA 13 BP 80 EP 80 PG 1 WC Hematology SC Hematology GA 907VH UT WOS:000227745600014 ER PT J AU Felsenfeld, G Burgess-Beusse, B Farrell, C Gaszner, M Ghirlando, R Huang, SM Jin, CY Nakatani, Y Litt, M Mutskov, V Tagami, H West, A Yusufzai, T AF Felsenfeld, G Burgess-Beusse, B Farrell, C Gaszner, M Ghirlando, R Huang, SM Jin, CY Nakatani, Y Litt, M Mutskov, V Tagami, H West, A Yusufzai, T TI A division of labor at the chicken beta-globin insulator. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 14th Conference on Hemoglobin Switching CY SEP 10-14, 2004 CL Orcas Isl, WA C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Ghirlando, Rodolfo/A-8880-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2005 VL 34 IS 2 MA 26 BP 86 EP 86 PG 1 WC Hematology SC Hematology GA 907VH UT WOS:000227745600027 ER PT J AU Orkin, SH AF Orkin, SH TI Studies of GATA-1 function. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 14th Conference on Hemoglobin Switching CY SEP 10-14, 2004 CL Orcas Isl, WA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, HHMI, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2005 VL 34 IS 2 MA 78 BP 110 EP 110 PG 1 WC Hematology SC Hematology GA 907VH UT WOS:000227745600079 ER PT J AU Zon, LI AF Zon, LI TI Hematopoietic stem cells in the zebrafish. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 14th Conference on Hemoglobin Switching CY SEP 10-14, 2004 CL Orcas Isl, WA C1 Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2005 VL 34 IS 2 MA 134 BP 134 EP 134 PG 1 WC Hematology SC Hematology GA 907VH UT WOS:000227745600135 ER PT J AU Marko, NF Frank, B Quackenbush, J Lee, NH AF Marko, NF Frank, B Quackenbush, J Lee, NH TI A robust method for the amplification of RNA in the sense orientation SO BMC GENOMICS LA English DT Article ID CDNA MICROARRAY ANALYSIS; GENE-EXPRESSION; SMALL NUMBERS; SINGLE; CELLS; NORMALIZATION; HYBRIDIZATION; CONSTRUCTION; TRANSCRIPTS; PROTOCOLS AB Background: Small quantities of RNA (1-4 mu g total RNA) available from biological samples frequently require a single round of amplification prior to analysis, but current amplification strategies have limitations that may restrict their usefulness in downstream genomic applications. The Eberwine amplification method has been extensively validated but is limited by its ability to produce only antisense RNA. Alternatives lack extensive validation and are often confounded by problems with bias or yield attributable to their greater biological and technical complexity. Results: To overcome these limitations, we have developed a straightforward and robust protocol for amplification of RNA in the sense orientation. This protocol is based upon Eberwine's method but incorporates elements of more recent amplification techniques while avoiding their complexities. Our technique yields greater than 100-fold amplification, generates long transcript, and produces mRNA that is well suited for use with microarray applications. Microarrays performed with RNA amplified using this protocol demonstrate minimal amplification bias and high reproducibility. Conclusion: The protocol we describe here is readily adaptable for the production of sense or antisense, labeled or unlabeled RNA from intact or partially-degraded prokaryotic or eukaryotic total RNA. The method outperforms several commercial RNA amplification kits and can be used in conjunction with a variety of microarray platforms, such as cDNA arrays, oligonucleotide arrays, and Affymetrix GeneChip (TM) arrays. C1 George Washington Univ, Sch Med, Washington, DC 20052 USA. George Washington Univ, Ctr Med, Dept Biochem & Mol Biol, Washington, DC 20052 USA. George Washington Univ, Ctr Med, Dept Pharmacol, Washington, DC 20052 USA. Dana Farber Canc Inst, TIGR, Dept Biostat & Computat Biol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Quackenbush, J (reprint author), George Washington Univ, Sch Med, Washington, DC 20052 USA. EM nmarko@tigr.org; bfrank@tigr.org; johnq@jimmy.harvard.edu; nhlee@tigr.org NR 39 TC 19 Z9 20 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 1 PY 2005 VL 6 AR 27 DI 10.1186/1471-2164-6-27 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 909XH UT WOS:000227893500001 PM 15740627 ER PT J AU Gyurko, R Shoji, H Battaglino, RA Boustany, G Gibson, FC Genco, CA Stashenko, P Van Dyke, TE AF Gyurko, R Shoji, H Battaglino, RA Boustany, G Gibson, FC Genco, CA Stashenko, P Van Dyke, TE TI Inducible nitric oxide synthase mediates bone development and P-gingivalis-induced alveolar bone loss SO BONE LA English DT Article DE osteoclasts; bone resorption; bone development; nitric oxide; iNOS ID PORPHYROMONAS-GINGIVALIS; OSTEOCLAST DIFFERENTIATION; PERIODONTAL-DISEASE; INDUCED ARTHRITIS; MINERAL DENSITY; MICE; RESORPTION; INHIBITION; EXPRESSION; ACTIVATION AB The role of inducible nitric oxide synthase (iNOS) in bone development and bacterially induced periodontal bone loss was examined using mice with targeted mutation of the NOS gene. Femurs of NOS KO mice showed 30% and 9% higher bone mineral density compared to wild type (WT) at 4 and 9 weeks of age, respectively. Micro-computed tornography revealed that cortical thickness and cortical bone density is increased in the absence of NOS, while trabecular bone thickness and bone density remains unchanged. Histochemical analysis using TRAP staining showed that osteoclast numbers are lower by 25% in iNOS KO femurs compared to WT femurs. When bone marrow cells were stimulated with M-CSF and RANKL in vitro, iNOS KO cultures developed 51% fewer TRAP-positive multinuclear cells compared to WT cultures. When similar cultures were grown on dentine discs, resorption pit area was decreased by 54% in NOS KO cultures. Gene expression studies showed that iNOS expression is induced by M-CSF and RANKL in WT bone marrow cultures, while no iNOS transcript was detected in iNOS KO. No compensatory change was detected in the expression of neuronal or endothelial NOS isofonns. There was no difference in RANK and osteoprotegerin expression between iNOS KO and WT bone marrow cultures after M-CSF and RANKL-treatment, while Traf6 expression was significantly lower in the absence of iNOS. In the alveolar bone of the maxilla, the distance between the cementoenamel junction and the alveolar bone crest was larger in iNOS KO compared to WT mice from 6 to 14 weeks of age, indicating a developmental effect of iNOS in oral tissues. Oral administration of the periodontal pathogen Porphyromonas gingivalis caused alveolar bone loss in the maxilla of WT mice, but failed to do so in iNOS KO mice. Expression of the osteoclast marker cathepsin K was 25% lower in iNOS KO alveolar bone. These data indicate that iNOS promotes bone resorption during bone development as well as after bacterial infection, and that NOS is an important signal for normal osteoclast differentiation. (c) 2004 Elsevier Inc. All rights reserved. C1 Boston Univ, Goldman Sch Grad Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Boston Univ, Med Ctr, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Microbiol, Boston, MA 02118 USA. RP Gyurko, R (reprint author), Boston Univ, Goldman Sch Grad Med, Dept Periodontol & Oral Biol, 100 E Newton St,Room 107, Boston, MA 02118 USA. EM gyurko@bu.edu RI battaglino, ricardo/D-2892-2015; OI Gyurko, Robert/0000-0003-1457-6812; Gibson, Frank/0000-0003-1988-1170 FU NIDCR NIH HHS [DE-13747, 1K22DE1456801A1, P01 DE013191, DE-09018, DE13191] NR 49 TC 35 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAR PY 2005 VL 36 IS 3 BP 472 EP 479 DI 10.1016/j.bone.2004.12.002 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914AN UT WOS:000228196900011 PM 15777672 ER PT J AU Panse, JP Heimfeld, S Guthrie, KA Maris, MB Maloney, DG Baril, BB Little, MT Chauncey, TR Storer, BE Storb, R Sandmaier, BM AF Panse, JP Heimfeld, S Guthrie, KA Maris, MB Maloney, DG Baril, BB Little, MT Chauncey, TR Storer, BE Storb, R Sandmaier, BM TI Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after non-myeloablative conditioning SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE graft composition; non-myeloablative transplantation; chimaerism ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; VERSUS-HOST-DISEASE; HEMATOPOIETIC PROGENITOR CELLS; UNRELATED DONORS; HEMATOLOGICAL MALIGNANCIES; IMMUNE RECONSTITUTION; ENGRAFTMENT KINETICS; LEUKEMIA; DEPLETION AB We have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20, natural killer (NK; CD3(-)/CD56(+)), NKT (CD3(+)/CD56(+)), DC1, and DC2 cells] of granulocyte colony-stimulating factor mobilized peripheral blood stem cells (PBSC) on early T-cell chimaerism and later clinical outcomes in 125 patients with haematological malignancies who received human leucocyte antigen (HLA)-matched related grafts after non-myeloablative conditioning. Conditioning consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI preceded by either 90 mg/m(2) fludarabine (n = 62) or planned autologous haematopoietic cell transplantation (HCT) (n = 35). Post-transplant immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate analysis showed that higher numbers of grafted NK cells predicted higher early T-cell chimaerism (P = 0.03), while higher numbers of B cells were associated with better clinical outcomes and a higher risk for chronic graft-versus-host disease (P = 0.05). Higher numbers of CD14(+) cells were associated with worse overall survival (P = 0.03), while higher numbers of CD34(+) cells showed better survival (P = 0.03). The addition of fludarabine or autologous HCT predicted higher early T-cell chimaerism (P = 0.001), while advanced donor age predicted lower chimaerism (P less than or equal to 0.02). Patients with aggressive diseases were at higher risk for relapse/disease progression, and shorter progression-free and overall survival (P < 0.01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post-HCT after non-myeloablative conditioning. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Dept Biostat, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM bsandmai@fhcrc.org FU NCI NIH HHS [CA 18029, P01 CA078902, CA 15704, CA 78902]; NHLBI NIH HHS [HL36444]; NIDDK NIH HHS [DK56465] NR 50 TC 47 Z9 48 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2005 VL 128 IS 5 BP 659 EP 667 DI 10.1111/j.1365-2141.2005.05363.x PG 9 WC Hematology SC Hematology GA 899XE UT WOS:000227178300011 PM 15725088 ER PT J AU Zhao, JC Chen, T AF Zhao, JC Chen, T TI Brinzolamide induced reversible corneal decompensation SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DORZOLAMIDE HYDROCHLORIDE; TOPICAL DORZOLAMIDE C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Glaucoma Serv, Boston, MA 02114 USA. RP Zhao, JC (reprint author), Progress Vis Inst, 201 E Laurel Blvd, Pottsville, PA 17901 USA. EM jcz2020@hotmail.com NR 7 TC 12 Z9 12 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAR PY 2005 VL 89 IS 3 BP 389 EP 390 DI 10.1136/bjo.2004.049544 PG 2 WC Ophthalmology SC Ophthalmology GA 902KF UT WOS:000227353900033 PM 15722328 ER PT J AU Mifflin, J AF Mifflin, J TI Doctors and patients: An anthology. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD SPR PY 2005 VL 79 IS 1 BP 176 EP 177 DI 10.1353/bhm.2005.0033 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 907QO UT WOS:000227733200043 ER PT J AU Mifflin, J AF Mifflin, J TI Medicine and literature: The doctor's companion to the classics. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD SPR PY 2005 VL 79 IS 1 BP 176 EP 177 DI 10.1353/bhm.2005.0033 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 907QO UT WOS:000227733200042 ER PT J AU Vandal, AC Gentleman, R Liu, XC AF Vandal, AC Gentleman, R Liu, XC TI Constrained estimation and likelihood intervals for censored data SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE constrained estimation; current status data; EM algorithm; interval censored data; interval estimation; nonparametric maximum likelihood; vertex exchange method ID MAXIMUM-LIKELIHOOD; EM ALGORITHM; CONFIDENCE-INTERVALS AB The authors propose a reduction technique and versions of the EM algorithm and the vertex exchange method to perform constrained nonparametric maximum likelihood estimation of the cumulative distribution function given interval censored data. The constrained vertex exchange method can be used in practice to produce likelihood intervals for the cumulative distribution function. In particular, the authors show how to produce a confidence interval with known asymptotic coverage for the survival function given current status data. C1 McGill Univ, Dept Math & Stat, Montreal, PQ H3A 2K6, Canada. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. SMBD Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3A 2K6, Canada. RP Vandal, AC (reprint author), McGill Univ, Dept Math & Stat, 805,Rue Sherbrooke Ouest, Montreal, PQ H3A 2K6, Canada. EM vandal@math.mcgill.ca; rgentlem@hsph.harvard.edu; liu@math.mcgill.ca NR 24 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD MAR PY 2005 VL 33 IS 1 BP 71 EP 83 PG 13 WC Statistics & Probability SC Mathematics GA 917NV UT WOS:000228470300005 ER PT J AU D'Amco, AV AF D'Amco, AV TI Screening for prostate carcinoma - Prostate-specific antigen - Friend or foe? SO CANCER LA English DT Editorial Material ID RADICAL PROSTATECTOMY; CANCER; TRIAL; ERA; OUTCOMES; TRENDS; RISK C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Amco, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM adamico@lroc.harvard.edu NR 15 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 JI Cancer PD MAR 1 PY 2005 VL 103 IS 5 BP 881 EP 883 DI 10.1002/cncr.20854 PG 3 WC Oncology SC Oncology GA 898ZH UT WOS:000227114200002 ER PT J AU Duan, ZF Lamendola, DE Duan, YF Yusuf, RZ Seiden, MV AF Duan, ZF Lamendola, DE Duan, YF Yusuf, RZ Seiden, MV TI Description of paclitaxel resistance-associated genes in ovarian and breast cancer cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE cDNA array; paclitaxel; chemotherapy; multidrug resistance ID MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; EXPRESSION; OVEREXPRESSION; PHENOTYPE; REVERSAL; SAMPLES; TAXOL; IL-8 AB Purpose: To identify genes involved in the paclitaxel resistance phenotype. Methods: High-density Affymetrix HG-U95Av2 microarrays were used to quantify gene expression in the resulting cell lines, SKOV-3(TR), OVCAR8(TR) and MCF-7(TR), and their drug-sensitive parental lines, SKOV-3, OVCAR8 and MCF-7. Results: Three paclitaxel-resistant human ovarian and breast cancer cell lines were established. We identified 790 (SKOV-3(TR)), 689 (OVCAR8(TR)) and 964 (MCF-7(TR)) transcripts that were more than twofold overexpressed relative to their expression in the corresponding parental cell line. A comparison of these transcripts identified eight genes that were significantly overexpressed in all three drug-resistant daughter cell lines. These genes included MDR1, a gene often implicated in both in vitro and in vivo resistance to multiple chemotherapeutics, including paclitaxel. The remaining seven genes have not been previously associated with resistance to paclitaxel in human cancer. Furthermore, we identified 815 (SKOV-3(TR)), 430 ( OVCAR8(TR)) and 332 (MCF-7(TR)) transcripts that were more than twofold decreased relative to their expression in the corresponding parental cell line. Comparison of these transcripts identified three genes that were significantly underexpressed in all three drug-resistant cell lines, none of which have been previously associated with paclitaxel resistance. Conclusions: Our results confirm that the paclitaxel resistance phenotype is associated with a large number of transcriptional changes. In addition, acquired paclitaxel resistance was associated with distinct transcriptional changes in each of the cell lines studied, suggesting that paclitaxel resistance is a complex phenotype that can arise through multiple mechanisms. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. EM zduan@partners.org OI Duan, Zhenfeng/0000-0002-8543-083X FU NCI NIH HHS [CA89150] NR 26 TC 54 Z9 58 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2005 VL 55 IS 3 BP 277 EP 285 DI 10.1007/s00280-004-0878-y PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 882BG UT WOS:000225912900010 PM 15565326 ER PT J AU Su, L Zhou, W Park, S Wain, JC Lynch, TJ Liu, G Christiani, DC AF Su, L Zhou, W Park, S Wain, JC Lynch, TJ Liu, G Christiani, DC TI Matrix metalloproteinase-1 promoter polymorphism and lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; TISSUE INHIBITORS; DIFFERENTIAL EXPRESSION; CELL CARCINOMA; BREAST-CANCER; TRANSCRIPTION; P53; GENE; SUSCEPTIBILITY; SMOKERS AB Extracellular matrix-degrading matrix metalloproteinase-1 (MMP-1) is an interstitial collagenase that degrades the interstitial types I, II, and III collagens, and overexpression of MMP-1 is associated with cancer development and cellular invasion. The 2 G allele of the MMP-1 - 1607 1G/2G polymorphism is associated with enhanced transcriptional activity. We investigated the association between the MMP-1 1G/2G polymorphism and lung cancer risk in 1,752 Caucasian lung cancer patients and 1,363 healthy controls. There were no overall associations between the MMP-1 genotypes and risk of lung cancer, with the adjusted odds ratios of 1.15 [95% confidence interval (CI), 0.94-1.40] for the 1G/2G genotype and 1.14 (95% CI, 0.90-1.45) for the 2G/2G genotype, when versus the 1G/1G genotype. Stratified analyses suggested higher lung cancer risk for the 2G allele in never-smokers and males, with the adjusted odds ratios of 1.67 (95% CI, 1.02-2.76; 1G/2G) and 1.50 (95% Cl, 0.86-2.62; 2G/2G) in never-smokers; and 1.30 (95% Cl, 1.00-1.75; 1G/2G) and 1.23 (95% CI, 0.88-1.73; 2G/2G) in males, respectively. In conclusion, genotypes containing the 2G allele of the MMP-1 polymorphism are associated with higher risk of lung cancer in never-smokers and in males. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA74386, CA 06409, CA90578]; NIEHS NIH HHS [ES 06409] NR 24 TC 38 Z9 42 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2005 VL 14 IS 3 BP 567 EP 570 DI 10.1158/1055-9965.EPI-04-0482 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 905CS UT WOS:000227545900005 PM 15767330 ER PT J AU Rudolph, RE Dominitz, JA Lampe, JW Levy, L Qu, PP Li, SYS Lampe, PD Bronner, MP Potter, JD AF Rudolph, RE Dominitz, JA Lampe, JW Levy, L Qu, PP Li, SYS Lampe, PD Bronner, MP Potter, JD TI Risk factors for colorectal cancer in relation to number and size of aberrant crypt foci in humans SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN COLON; QUANTIFICATION; INSTABILITY; CARCINOGENESIS; IDENTIFICATION; PROGRESSION; DYSPLASIA; DISEASE; RATS AB Several characteristics of aberrant crypt foci (ACF) suggest that they are precursors of colorectal cancer, but the factors that promote or inhibit their growth are largely unknown. We conducted a pilot study to explore whether factors associated with risk of colorectal cancer are also associated with number or size of rectal ACF. Thirty-two U.S. veterans, ages 50 to 80 years, were recruited to undergo magnifying chromoendoscopy for imaging of rectal ACF and colonoscopy for identification of polyps or cancer. Participants completed a questionnaire on cigarette smoking, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and family history of colorectal cancer. Fisher's exact test was used to assess the statistical significance of associations between colorectal cancer risk factors and characteristics of ACF. Cochran-Mantel-Haenszel statistics and polytomous regression were used to test the significance of associations adjusted for age. Participants with a history of adenoma had more ACF than those without (age-adjusted P = 0.02), but the numbers in the two groups overlapped markedly. Older participants had more (P = 0.06) and larger (P = 0.009) ACF than younger participants. No associations were identified between either ACF number or size and cigarette smoking, use of NSAIDs, or family history of colorectal cancer. These findings suggest that persons with adenomas have somewhat more rectal ACF than persons without, and that older age is a risk factor for ACF growth. Future research should be directed toward developing techniques to identify ACF that are likely to progress to cancer and the modifiable factors that promote or inhibit such progression. C1 Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. RP Rudolph, RE (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, POB 19024,M3-B232, Seattle, WA 98109 USA. EM rrudolph@fhcrc.org OI Potter, John/0000-0001-5439-1500; Dominitz, Jason/0000-0002-8070-7086 FU NCI NIH HHS [P01 CA074184] NR 24 TC 46 Z9 50 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2005 VL 14 IS 3 BP 605 EP 608 DI 10.1158/1055-9965.EPI-04-0058 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 905CS UT WOS:000227545900012 PM 15767337 ER PT J AU Kim, JY Hecht, SS Mukherjee, S Carmella, SG Rodrigues, EG Christiani, DC AF Kim, JY Hecht, SS Mukherjee, S Carmella, SG Rodrigues, EG Christiani, DC TI A urinary metabolite of phenanthrene as a biomarker of polycyclic aromatic hydrocarbon metabolic activation in workers exposed to residual oil fly ash SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COKE-OVEN WORKERS; FUEL-OIL; 1-HYDROXYPYRENE CONCENTRATIONS; BENZO(A)PYRENE; BOILERMAKERS; COMBUSTION; ADDUCTS; PYRENE; COAL AB Residual oil fly ash is a chemically complex combustion product containing a significant component of potentially carcinogenic transition metals and polycyclic aromatic hydrocarbons (PAH). Various biomarkers of PAH exposure have been investigated previously, most notably 1-hydroxypyrene (1-OHP), in urine. In this study, we assessed the utility of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT), a metabolite of phenanthrene, to detect occupational PAH exposure. Urine samples collected across the workweek were analyzed for 1-OHP and trans, anti-PheT in boilermakers (n = 20) exposed to residual oil fly ash. Median baseline urinary trans, anti-PheT concentrations were 0.50 mu g/g creatinine in current tobacco smokers and 0.39 mu g/g creatinine in nonsmokers. Median baseline urinary 1-OHP concentrations in smokers and nonsmokers were 0.31 and 0.13 mu g/g creatinine, respectively. To study further the effect of smoking exposure on the urinary PAH markers, urinary cotinine was used. Although urinary trans, anti-PheT and 1-OHP concentrations were correlated (Spearman r = 0.63; P < 0.001) for all subjects, the regression coefficient between log-transformed trans, anti-PheT and log 1-OHP was statistically significant only for subjects with low levels of urinary cotinine or for nonsmokers. Each 1-unit increase in log 1-OHP was associated with a 0.77-unit increase (95% confidence interval, 0.45-1.09) in log trans, anti-PheT in subjects with low levels of urinary cotinine (P < 0.001). In these subjects, dichotomized occupational exposure status was a significant predictor of log trans, anti-PheT (P = 0.02) but not of log 1-OHP (P = 0.2). In conclusion, we found that urinary trans, anti-PheT was detected in levels comparable with 1-OHP in occupationally exposed workers, particularly nonsmokers. This study shows that urinary trans, anti-PheT may be an effective biomarker of uptake and metabolic activation of PAHs. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1402,665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu OI Hecht, Stephen/0000-0001-7228-1356 FU NCI NIH HHS [CA92025, CA94715]; NIEHS NIH HHS [ES00002, ES09860, T32 ES07069] NR 32 TC 18 Z9 18 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2005 VL 14 IS 3 BP 687 EP 692 DI 10.1158/1055-9965.EPI-04-0428 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 905CS UT WOS:000227545900025 PM 15767350 ER PT J AU Beard, CJ AF Beard, CJ TI The risk of bladder, bowel, and sexual dysfunction after radiation therapy: What the data tell us and how we can use it to counsel our patients SO CANCER JOURNAL LA English DT Editorial Material ID QUALITY-OF-LIFE; LOCALIZED PROSTATE-CANCER; EXTERNAL-BEAM RADIATION; ERECTILE DYSFUNCTION; RADICAL PROSTATECTOMY; BRACHYTHERAPY; OUTCOMES; MEN; SYMPTOMS; PREFERENCES C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Beard, CJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,Tower L2 ASB1, Boston, MA 02115 USA. NR 32 TC 1 Z9 1 U1 1 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2005 VL 11 IS 2 BP 106 EP 109 DI 10.1097/00130404-200503000-00004 PG 4 WC Oncology SC Oncology GA 927DN UT WOS:000229172700004 PM 15969984 ER PT J AU Peters, N Armstrong, K AF Peters, N Armstrong, K TI Racial differences in prostate cancer treatment outcomes - A systematic review SO CANCER NURSING LA English DT Article DE African Americans; blacks; prostate cancer; prostate neoplasm; treatment outcome ID AFRICAN-AMERICAN MEN; DISEASE-FREE SURVIVAL; ACCESS MEDICAL-CENTER; RADICAL PROSTATECTOMY; WHITE MEN; RADIATION-THERAPY; INDEPENDENT PREDICTOR; HEALTH-CARE; PROGNOSTIC-SIGNIFICANCE; BIOCHEMICAL RECURRENCE AB Although differences in prostate cancer incidence and mortality between black and white men are widely accepted, the existence of racial differences in treatment outcomes remains controversial. We conducted a systematic review of racial differences in prostate cancer treatment outcomes. Systematic review of literature from 1992-2002 was conducted. Database searches were performed using the terms: "prostate cancer" (keyword) or "prostate neoplasm" (subject heading) + "blacks" (subject heading) or "blacks" (keyword) + "African-Americans" (subject heading) or "African-Americans" (keyword). Two hundred fifty-eight relevant articles were identified; 29 fit the inclusion criteria. All but 3 were retrospective. Seven (24%) studies were conducted at Veterans Affairs medical centers. Treatment included radical prostatectomy (15 studies), hormonal therapy (5 studies), and radiotherapy (12 studies). Three studies included more than 1 treatment. Twenty-three (79%) studies, observed no significant difference in treatment outcomes between races. The remainder found worse outcomes among black men, including worse 5-year survival (HR range, 2.35-96.74) and higher rates of PSA failure (OR range, 1.15-1.69). Most studies Investigating racial differences in prostate cancer treatment outcomes over the past 10 years found no difference between races after controlling for tumor and patient characteristics. Efforts to narrow the gap between black and white prostate cancer mortality should focus on ensuring that all patients receive optimal treatment and that all patients become informed about the use of screening for early cancer detection. Research should focus on interventions to reduce advanced presentation of the disease and disease-related mortality among black men. C1 Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Peters, N (reprint author), 1101 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM npeters@nursing.upenn.edu NR 51 TC 41 Z9 41 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2005 VL 28 IS 2 BP 108 EP 118 PG 11 WC Oncology; Nursing SC Oncology; Nursing GA 916UE UT WOS:000228410900004 PM 15815180 ER PT J AU Goldmann, WH Cantiello, HF Chasan, B AF Goldmann, WH Cantiello, HF Chasan, B TI Actomyosin II interaction modulates cell cortex stability SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE actin filaments; myosin II; rheology; atomic force microscopy ID LINKED ACTIN NETWORKS; MYOSIN-II; PHOSPHORYLATION; MOTILITY AB Myosin II controls the viscoelastic behavior of actin filaments, interacting with actin in an energy-dependent manner. Replacing adenosine triphosphate with adenosine diphosphate changes actomyosin sliding to cross-linking. Rheological measurements show a 3-4-fold increase of the elastic portion G' in actin filaments when myosin II is present at a molar ratio r(MA) = 1:200. This observation is supported by the demonstration of inactive myosin heads along actin filaments using atomic force microscopy. (C) 2005 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. C1 Univ Erlangen Nurnberg, Zent Inst Biomed Tech, Lehrstuhl Phys Med Tech, D-91052 Erlangen, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Boston Univ, Dept Phys, Boston, MA 02215 USA. RP Goldmann, WH (reprint author), Univ Erlangen Nurnberg, Zent Inst Biomed Tech, Lehrstuhl Phys Med Tech, Henkestr 91, D-91052 Erlangen, Germany. EM wgoldmann@biomed.uni-erlangen.de RI Goldmann, Wolfgang/H-5572-2013 NR 16 TC 5 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD MAR PY 2005 VL 29 IS 3 BP 245 EP 248 DI 10.1016/j.cellbi.2004.12.003 PG 4 WC Cell Biology SC Cell Biology GA 936TF UT WOS:000229877600009 PM 15908238 ER PT J AU Kozar, K Sicinski, P AF Kozar, K Sicinski, P TI Cell cycle progression without cyclin D-CDK4 and cyclin D-CDK6 complexes SO CELL CYCLE LA English DT Article DE cyclins; cyclin-dependent kinases; cell cycle; mouse knockout; hematopoiesis ID MAMMARY-GLAND DEVELOPMENT; SKIN TUMOR-DEVELOPMENT; ESTROGEN-RECEPTOR; RETINOBLASTOMA-PROTEIN; DEPENDENT KINASES; CDK INHIBITORS; GROWTH SUPPRESSION; D1-DEFICIENT MICE; D1 PROTEIN; EXPRESSION AB D-type cyclins ( cyclin D1, D2 and D3) and their associated cyclin-dependent kinases CDK4 and CDK6 were thought to represent important, perhaps essential components of the core cell cycle apparatus. However, recent analyses of mice lacking D-cyclins, or CDK4 and CDK6 reveal that these proteins are critically required for proliferation only in the selected cell types. Intriguingly, several compartments can develop in the absence of cyclin D-CDK4/6 activity, revealing that these cells can proliferate in a cyclin D-independent fashion. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Med Univ Warsaw, Ctr Biostruct Res, Dept Immunol, Warsaw, Poland. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 48 Binney St, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [R01 CA108420] NR 60 TC 67 Z9 68 U1 1 U2 6 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR PY 2005 VL 4 IS 3 BP 388 EP 391 DI 10.4161/cc.4.3.1551 PG 4 WC Cell Biology SC Cell Biology GA 932FB UT WOS:000229538500012 PM 15738651 ER PT J AU Precht, TA Phelps, RA Linseman, DA Butts, BD Le, SS Laessig, TA Bouchard, RJ Heidenreich, KA AF Precht, TA Phelps, RA Linseman, DA Butts, BD Le, SS Laessig, TA Bouchard, RJ Heidenreich, KA TI The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE cerebellar granule neurons; cytochrome c; cyclosporin A; Bcl-2 family ID CYTOCHROME-C RELEASE; CEREBELLAR GRANULE NEURONS; BCL-2 FAMILY PROTEINS; GROWTH-FACTOR-I; CELL-DEATH; CASPASE ACTIVATION; BIM; POTASSIUM; CHANNEL; COMPLEX AB Cerebellar granule neurons (CGNs) require depolarization for their survival in culture. When deprived of this stimulus, CGNs die via an intrinsic apoptotic cascade involving Bim induction, Bax translocation, cytochrome c release, and caspase-9 and -3 activation. Opening of the mitochondrial permeability transition pore (mPTP) is an early event during intrinsic apoptosis; however, the precise role of mPTP opening in neuronal apoptosis is presently unclear. Here, we show that mPTP opening acts as an initiating event to stimulate Bax translocation to mitochondria. A C-terminal (alpha9 helix) GFP-Bax point mutant (T182A) that constitutively localizes to mitochondria circumvents the requirement for mPTP opening and is entirely sufficient to induce CGN apoptosis. Collectively, these data indicate that the major role of mPTP opening in CGN apoptosis is to trigger Bax translocation to mitochondria, ultimately leading to cytochrome c release and caspase activation. C1 Univ Colorado, Hlth Sci Ctr Fitzsimons, Dept Pharmacol, Aurora, CO 80045 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr Fitzsimons, Dept Pharmacol, POB 6511,Mail Stop 8303, Aurora, CO 80045 USA. EM Kim.Heidenreich@UCHSC.edu NR 42 TC 57 Z9 60 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAR PY 2005 VL 12 IS 3 BP 255 EP 265 DI 10.1038/sj.cdd.4401552 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 897ME UT WOS:000227007500006 PM 15637643 ER PT J AU Bates, SH Kulkarni, RN Seifert, M Myers, MG AF Bates, SH Kulkarni, RN Seifert, M Myers, MG TI Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis SO CELL METABOLISM LA English DT Article ID REVERSES INSULIN-RESISTANCE; OB/OB MICE; CONGENITAL LIPODYSTROPHY; OBESE GENE; DB/DB MICE; IN-VIVO; RECEPTOR; ACTIVATION; METABOLISM; WEIGHT AB Leptin activates the long form of the leptin receptor (LRb) to control feeding and neuroendocrine function and thus regulate adiposity. While adiposity influences insulin sensitivity, leptin also regulates glucose homeostasis independently of energy balance. Disruption of the LRb/STAT3 signal in s/s mice results in hyperphagia, neuroendocrine dysfunction, and obesity similar to LRb null db/db mice. Insulin resistance and glucose intolerance are improved in s/s compared to db/db animals, however, suggesting that LRb/STAT3-independent signals may contribute to the regulation of glucose homeostasis by leptin. Indeed, caloric restriction normalized glycemic control in s/s animals, but db/db mice of similar weight and adiposity remained hyperglycemic. These differences in glucose homeostasis were not attributable to differences in insulin production between s/s and db/db animals but rather to decreased insulin resistance in s/s mice. Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control. C1 Univ Michigan, Dept Internal Med, Div Endocrinol Diabet & Metab, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Myers, MG (reprint author), Univ Michigan, Dept Internal Med, Div Endocrinol Diabet & Metab, Ann Arbor, MI 48109 USA. EM mgmyers@umich.edu FU NIDDK NIH HHS [DK57768]; PHS HHS [56731] NR 46 TC 81 Z9 90 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAR PY 2005 VL 1 IS 3 BP 169 EP 178 DI 10.1016/j.cmet.2005.02.001 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 922IM UT WOS:000228830600005 PM 16054060 ER PT J AU Tang, D Khaleque, A Jones, EL Theriault, JR Li, C Wong, WH Stevenson, MA Calderwood, SK AF Tang, D Khaleque, A Jones, EL Theriault, JR Li, C Wong, WH Stevenson, MA Calderwood, SK TI Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo SO CELL STRESS & CHAPERONES LA English DT Article ID HUMAN BREAST-CANCER; ALPHA-B-CRYSTALLIN; HUMAN HSP70; CELL-LINE; NUCLEOTIDE-SEQUENCE; TRANSCRIPTIONAL REGULATION; PROGNOSTIC-SIGNIFICANCE; MOLECULAR-CLONING; GENE; FAMILY AB Heat shock proteins (HSPs) are thought to play a role in the development of cancer and to modulate tumor response to cytotoxic therapy. In this study, we have examined the expression of hsf and HSP genes in normal human prostate epithelial cells and a range of prostate carcinoma cell lines derived from human tumors. We have observed elevated expressions of HSF1, HSP60, and HSP70 in the aggressively malignant cell lines PC-3, DU-145, and CA-HPV-10. Elevated HSP expression in cancer cell lines appeared to be regulated at the post-messenger ribonucleic acid (mRNA) levels, as indicated by gene chip microarray studies, which indicated little difference in heat shock factor (HSF) or HSP mRNA expression between the normal and malignant prostate cell lines. When we compared the expression patterns of constitutive HSP genes between PC-3 prostate carcinoma cells growing as monolayers; in vitro and as tumor xenografts growing in nude mice in vivo, we found a marked reduction in expression of a wide spectrum of the HSPs in PC-3 tumors. This decreased HSP expression pattern in tumors may underlie the increased sensitivity to heat shock of PC-3 tumors. However, the induction by heat shock of HSP genes was not markedly altered by growth in the tumor microenvironment, and HSP40, HSP70, and HSP110 were expressed abundantly after stress in each growth condition. Our experiments indicate therefore that HSF and HSP levels are elevated in the more highly malignant prostate carcinoma cells and also show the dominant nature of the heat shock-induced gene expression, leading to abundant HSP induction in vitro or in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM scalderw@bidmc.harvard.edu FU NCI NIH HHS [CA50642, CA77465, R01 CA077465, R01 CA047407, CA47407, CA31303] NR 79 TC 102 Z9 116 U1 0 U2 5 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD SPR PY 2005 VL 10 IS 1 BP 46 EP 58 DI 10.1379/CSC-44R.1 PG 13 WC Cell Biology SC Cell Biology GA 908HM UT WOS:000227778100008 PM 15832947 ER PT J AU Monnard, PA AF Monnard, PA TI Catalysis in abiotic structured media: an approach to selective synthesis of biopolymers SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE biocatalysis; micro- and nanoenvironment; compartmentalization; amphiphile structures; eutectic phase in water ice; minerals; synthesis and selection of RNA and proteins ID TEMPLATE-DIRECTED SYNTHESIS; IN-VITRO SELECTION; ALPHA-AMINO-ACIDS; CRYO-BIOORGANIC CHEMISTRY; SELF-REPRODUCING VESICLES; RNA RANDOM COPOLYMERS; NUCLEIC-ACIDS; MONTMORILLONITE CATALYSIS; HAIRPIN OLIGONUCLEOTIDES; REVERSE MICELLES AB Micro- and nanoenvironments formed by amphiphile self-assembled structures, water-ice lattices and minerals have well-defined, repeating, chemical and physical properties that can be used for selective synthesis of biopolymers, such as RNAs and proteins. The advances made in the development of polymerization supported by these micro- and nanosystems are reviewed here. In particular, it is shown that these systems promote non-enzymatic biopolymerization, yielding long polymers whose sequence composition is determined by the interactions between monomers and the supporting environment. When used to compartmentalize enzymatic biopolymerization, micro- and nanostructures allow the implementation of molecular selection and evolution schemes, which are difficult in homogeneous medium, yielding very active molecules. Thus, micro- and nanoenvironment approaches to the synthesis and selection of biopolymers could be developed into a new biotechnological tool for the production of biopolymers with novel functions. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Monnard, PA (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Wellman 9,50 Blossom St, Boston, MA 02114 USA. EM monnard@molbio.mgh.harvard.de NR 114 TC 20 Z9 20 U1 0 U2 10 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2005 VL 62 IS 5 BP 520 EP 534 DI 10.1007/s00018-004-4342-2 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 903OS UT WOS:000227436000003 PM 15747059 ER PT J AU Fu, MG Zhang, JF Tseng, YH Cui, TX Zhu, XJ Xiao, Y Mou, YS De Leon, H Chang, MMJ Hamamori, Y Kahn, CR Chen, YQE AF Fu, MG Zhang, JF Tseng, YH Cui, TX Zhu, XJ Xiao, Y Mou, YS De Leon, H Chang, MMJ Hamamori, Y Kahn, CR Chen, YQE TI Rad GTPase attenuates vascular lesion formation by inhibition of vascular smooth muscle cell migration SO CIRCULATION LA English DT Article DE atherosclerosis; cell movement; cells, vascular smooth muscle; monomeric GTP-binding proteins; restenosis ID RHO-KINASE PATHWAY; GROWTH-FACTOR; SIGNALING PATHWAY; PROTEIN; FAMILY; MEMBER; ATHEROSCLEROSIS; ACTIVATION; PROMOTES; GEM AB Background - Rad (Ras associated with diabetes) GTPase is a prototypic member of a new subfamily of Ras-related GTPases with unique structural features, although its physiological role remains largely unknown. In the present study, we characterized the Rad function in vascular smooth muscle cells (VSMCs) and the influence of adenovirus-mediated Rad (Ad-Rad) gene delivery on vascular remodeling after experimental angioplasty. Methods and Results - We documented for the first time that neointimal formation using balloon-injured rat carotid arteries was associated with a significant increase in Rad expression as determined by immunohistochemistry and quantitative real-time reverse-transcriptase polymerase chain reaction. The levels of Rad expression in VSMCs were highly induced by platelet-derived growth factor and tumor necrosis factor-alpha. Morphometric analyses 14 days after injury revealed significantly diminished neointimal formation in the Ad-Rad-treated carotid arteries compared with Ad-GFP or PBS controls, whereas the mutated form of Rad GTPase, which can bind GDP but not GTP, increased neointimal formation. Overexpression of Rad significantly inhibited the attachment and migration of VSMCs. In addition, Rad expression dramatically reduced the formation of focal contacts and stress fibers in VSMCs by blocking the Rho/ROK signaling pathway. Conclusions - Our data clearly identified Rad GTPase as a novel and critical mediator that inhibits vascular lesion formation. Manipulation of the Rad signaling pathway may provide new therapeutic approaches that will limit vascular pathological remodeling. C1 Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Dept Med, Boston, MA 02115 USA. Peking Univ, Ctr Hlth Sci, Cardiovasc Res Inst, Beijing 100871, Peoples R China. Univ Calif Davis, Ctr Comparat Resp Biol & Med, Sch Med, Davis, CA 95616 USA. Baylor Coll Med, Dept Med, Ctr Cardiovasc Dev, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA. RP Chen, YQE (reprint author), Morehouse Sch Med, Cardiovasc Res Inst, 720 Westview Dr SW, Atlanta, GA 30310 USA. EM echen@msm.edu OI Cui, Taixing/0000-0002-9528-7299 FU NCRR NIH HHS [G12-RR03034]; NHLBI NIH HHS [HL-03676]; NIGMS NIH HHS [S06GM08248] NR 35 TC 32 Z9 32 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 MAR 1 PY 2005 VL 111 IS 8 BP 1071 EP 1077 DI 10.1161/01.CIR.0000156439.55349.AD PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 901ST UT WOS:000227302900018 PM 15710763 ER PT J AU Wen, PY AF Wen, PY TI A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ADVANCED COLORECTAL-CANCER; OVARIAN-CANCER; CISPLATIN; NEUROTOXICITY; PACLITAXEL; AMIFOSTINE; ANALOG; DEATH C1 Brigham & Womens Hosp, Dept Neurol, Dana Farber Canc Inst, Ctr Neurooncol,Div Neurooncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Dana Farber Canc Inst, Ctr Neurooncol,Div Neurooncol, 44 Binney St, Boston, MA 02115 USA. EM Patrick_wen@dfci.harvard.edu NR 23 TC 5 Z9 5 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 MAR 1 PY 2005 VL 11 IS 5 BP 1685 EP 1686 DI 10.1158/1078-0432.CCR-04-2583 PG 2 WC Oncology SC Oncology GA 903IT UT WOS:000227420100001 PM 15755987 ER PT J AU George, DJ Halabi, S Shepard, TF Sanford, B Vogelzang, NJ Small, EJ Kantoff, PW AF George, DJ Halabi, S Shepard, TF Sanford, B Vogelzang, NJ Small, EJ Kantoff, PW TI The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: Results from cancer and leukemia group B 9480 SO CLINICAL CANCER RESEARCH LA English DT Article ID AUTOCRINE GROWTH-FACTOR; ANDROGEN RECEPTOR; NEUROENDOCRINE DIFFERENTIATION; CARCINOMA-CELLS; CASTLEMANS-DISEASE; SIGNAL TRANSDUCER; TUMOR-CELLS; GROUP-B; LNCAP; STAT3 AB Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480.(CALGB 9480)]. Methods: 191 patients entered on CALGB 9480 had pretreatment plasma collected and centrally stored. Using a human IL-6 immunoassay, quantitative levels of IL-6 were measured in duplicate on 300 muL samples. The proportional hazard model was used to assess the prognostic significance of IL-6 in predicting overall survival. Results: Median IL-6 level for the cohort of 191 patients was 4.80 pg/mL. Survival time among patients with IL-6 levels less than or equal to the median was 19 months (95% CI, 17-22) compared with 11 (95% CI, 8-14) months for patients above the median (P = 0.0004). In multivariate analysis, adjusting on performance status, lactate dehydrogenase, and prostate-specific antigen level, the hazard ratio was 1.38 (95% CI, 1.01-1.89; P = 0.043) using the median level as a cut point. Furthermore, a cut point of 13.31 pg/mL revealed robust prognostic significance with a hazard ratio of 2.02 (95% CI, 1.36-2.98; P = 0.0005). Conclusions: Plasma IL-6 level has prognostic significance in patients with metastatic HRCaP from CALGB 9480. These findings support using IL-6 levels in prognostic models and support the rationale for IL-6-targeted therapy in patients with HRCaP. C1 Duke Univ, Med Ctr, Canc & Leukemia Grp B, Ctr Stat,Div Urol, Durham, NC 27706 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp B, Ctr Stat,Div Med Oncol, Durham, NC 27706 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Univ Calif San Francisco, Mt Zion Canc Ctr, San Francisco, CA 94143 USA. Nevada Canc Inst, Las Vegas, NV USA. RP George, DJ (reprint author), Duke Clin Res Inst, Box 3850 DUMC, Durham, NC 27710 USA. EM georg033@mc.duke.edu FU NCI NIH HHS [CA 31946] NR 42 TC 93 Z9 97 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 MAR 1 PY 2005 VL 11 IS 5 BP 1815 EP 1820 DI 10.1158/1078-0432.CCR-04-1560 PG 6 WC Oncology SC Oncology GA 903IT UT WOS:000227420100018 PM 15756004 ER PT J AU Isman, F Palomaki, GE Natowicz, MR AF Isman, F Palomaki, GE Natowicz, MR TI Lysosomal enzymes in human peripheral blood mononuclear cells and granulocytes SO CLINICAL CHEMISTRY LA English DT Article ID UNUSUAL THERMOLABILITY PROPERTIES; BETA-HEXOSAMINIDASE; STORAGE DISEASES; ARYLSULFATASE-A; LEUKOCYTES; POPULATIONS; FIBROBLASTS; HYDROLASES; ISOENZYMES C1 Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Med Genet, Waltham, MA USA. Fdn Blood Res, Scarborough, ME 04074 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Natowicz, MR (reprint author), Cleveland Clin Fdn, Dept Neurol, S-71,9500 Euclid Ave, Cleveland, OH 44195 USA. EM natowim@ccf.org NR 26 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2005 VL 51 IS 3 BP 646 EP 649 DI 10.1373/clinchem.2004.045930 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 900QY UT WOS:000227230600027 PM 15637131 ER PT J AU Lee, LS Saltzman, JR Bounds, BC Poneros, JM Brugge, WR Thompson, CC AF Lee, LS Saltzman, JR Bounds, BC Poneros, JM Brugge, WR Thompson, CC TI EUS-guided fine needle aspiration of pancreatic cysts: A retrospective analysis of complications and their predictors SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID ENDOSCOPIC ULTRASOUND; DIAGNOSTIC-ACCURACY; BIOPSY; LESIONS; ENDOSONOGRAPHY; UTILITY; MASSES; HEMORRHAGE; FREQUENCY; OUTCOMES AB Background & Aims: Endoscopic ultrasound- guided fine-needle aspiration (EUS FNA) of pancreatic cysts is considered safe, however, data are conflicting regarding complication rates. The aim of this study was to determine the complication rate of EUS-guided pancreatic cyst aspiration and predictors of these complications. Methods: Results of pancreatic cyst EUS FNA at 2 academic institutions from March :1996 to October 2003 were reviewed. A total of 603 patients with 651 pancreatic cysts were evaluated. Complications were identified from clinic, emergency department, and discharge notes, and laboratory and radiologic data. Data collected were as follows: cyst size, location, septations, diagnosis, number of passes, needle size, status as inpatient or outpatient, performance of same-day endoscopic retrograde cholangiopancreatography (ERCP), and use of prophylactic antibiotics. Results: Complications were identified in 13 patients (2.2%, 13 of 603): 6 patients had pancreatitis, 4 patients had abdominal pain, :1 patient had a retroperitoneal bleed, 1. patient had an infection, and :1 patient had bradycardia. Twelve patients required hospitalization, with an average length of stay of 3.8 +/- 11 days. Type of cyst, size, presence of septations or mass, and same-day ERCP were not predictors of complications. Conclusions: EUS-guided pancreatic cyst aspiration carries a low complication rate similar to that reported for solid pancreatic lesions. No patient or cyst characteristics appear to be predictive of adverse events. C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 93 Z9 94 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2005 VL 3 IS 3 BP 231 EP 236 DI 10.1053/S1542-3565(04)00618-4 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995MS UT WOS:000234105000007 PM 15765442 ER PT J AU Gavrila, A Hsu, W Tsiodras, S Doweiko, J Gautam, S Martin, L Moses, AC Karchmer, AW Mantzoros, CS AF Gavrila, A Hsu, W Tsiodras, S Doweiko, J Gautam, S Martin, L Moses, AC Karchmer, AW Mantzoros, CS TI Improvement in highly active antiretroviral therapy-induced metabolic syndrome by treatment with pioglitazone but not with fenofibrate: A 2 x 2 factorial, randomized, double-blinded, placebo-controlled trial SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ROSIGLITAZONE; HYPERLIPIDEMIA; LIPODYSTROPHY AB We designed a factorial, randomized, double-blinded, 2 x 2 placebo-controlled trial to evaluate the effects of treatment with pioglitazone and/or fenofibrate in patients with highly active antiretroviral therapy (HAART)-induced metabolic syndrome. We found that the administration of pioglitazone, but not fenofibrate, improved insulin resistance, blood pressure, and lipid profile over a 12-month period. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Translat Res, Dept Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, 330 Brookline Ave,ST 820, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu OI Tsiodras, Sotirios/0000-0002-0463-4321 FU NCRR NIH HHS [M01-RR 01032]; NHLBI NIH HHS [K30 HL04095] NR 12 TC 37 Z9 38 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 MAR 1 PY 2005 VL 40 IS 5 BP 745 EP 749 DI 10.1086/427697 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JO UT WOS:000227492700017 PM 15714423 ER PT J AU Treon, SP Morel, P Leblond, V Fermand, JP AF Treon, SP Morel, P Leblond, V Fermand, JP TI Report of the third international workshop on Waldenstrom's macroglobulinemia SO CLINICAL LYMPHOMA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Hosp Schaffner, Lens, France. Hop La Pitie Salpetriere, Paris, France. Hop St Louis, Paris, France. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [K23 CA 087977-03] NR 0 TC 16 Z9 16 U1 0 U2 0 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD MAR PY 2005 VL 5 IS 4 BP 215 EP 216 DI 10.3816/CLM.2005.n.001 PG 2 WC Oncology SC Oncology GA 981HK UT WOS:000233078100001 PM 15794850 ER PT J AU Hunter, ZR Branagan, AR Manning, R Patterson, CJ Santos, DD Tournilhac, O Dorfman, DM Treon, SP AF Hunter, ZR Branagan, AR Manning, R Patterson, CJ Santos, DD Tournilhac, O Dorfman, DM Treon, SP TI CD5, CD10, and CD23 expression in Waldenstrom's macroglobulinemia SO CLINICAL LYMPHOMA LA English DT Article; Proceedings Paper CT 3rd International Workshop on Waldenstroms Macroglobulinemia CY OCT 07-10, 2004 CL Paris, FRANCE SP Int Waldenstroms Macroglobulinemia Fdn, Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia DE B-cell disorder; bone marrow lymphoplasmacytic cells; hyperviscosity ID IMMUNOPHENOTYPIC ANALYSIS; CLASSIFICATION; LYMPHOMA AB CD5, CD10, and CD23 are cell surface antigens used to distinguish B-cell disorders. The expression of these antigens and their clinical significance in Waldenstrom's macroglobulinemia (WM), an uncommon B-cell disorder, remains to be clarified. We therefore determined expression of CD5, CD10, and CD23 by flow cytometric analysis on bone marrow lymphoplasmacytic cells (CD19(+) kappa/lambda light chain restricted) for 171 serially biopsied patients with findings of the consensus panel definition of WM. Importantly, we also correlated laboratory and clinical data, as well as existence of a familial history of a B-cell disorder in view of reports suggesting familial predisposition in WM. These studies demonstrated tumor cell expression of CD5, CD10, and CD23 in 15 of 171 patients (9%), 11 of 161 patients (7%), and 37 of 105 patients (35%), respectively. Coexpression of CD23 with CD5 or CD10 was common, Tumor Lymphoplasmacytic from 10 of 15 (66%) and 3 of 11 (27%) patients with WM that expressed CD5 and 010, respectively, also showed expression of CD23 (P = 0.01 and P = 0.08, respectively). Among patients with CD23 expression, increased serum immunoglobulin (Ig) M levels were observed compared with patients without CD23 expression (P = 0.05). No differences in age at diagnosis; presence of adenopathy and/or splenomegaly; bone marrow involvement; serum IgA, IgB, and beta 2 macroglobulin levels; hematocrit; platelet count; or familial history of WM or a related B-cell disorder were observed among patients with and without CD5, CD10, and CD23 expression. These studies demonstrate that CD5, 010, and CD23 are commonly found in WM and that their expression should not exclude the diagnosis of WM. Moreover, expression of CD23 may define a clinically distinct subset of patients with WM. C1 Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, LG 102,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Branagan, Andrew/0000-0002-3868-9267 FU NCI NIH HHS [K23 CA 087977-03] NR 9 TC 27 Z9 30 U1 0 U2 1 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD MAR PY 2005 VL 5 IS 4 BP 246 EP 249 DI 10.3816/CLM.2005.n.008 PG 4 WC Oncology SC Oncology GA 981HK UT WOS:000233078100008 PM 15794857 ER PT J AU Adamia, S Treon, SP Reiman, T Tournilhac, O McQuarrie, C Mant, MJ Belch, AR Pilarski, LM AF Adamia, S Treon, SP Reiman, T Tournilhac, O McQuarrie, C Mant, MJ Belch, AR Pilarski, LM TI Potential impact of a single nucleotide polymorphism in the hyaluronan synthase 1 gene in Waldenstrom's macroglobulinemia SO CLINICAL LYMPHOMA LA English DT Article; Proceedings Paper CT 3rd International Workshop on Waldenstroms Macroglobulinemia CY OCT 07-10, 2004 CL Paris, FRANCE SP Int Waldenstroms Macroglobulinemia Fdn, Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia DE exonic splicing enhancer; hyaluronan; splicing factor ID PRE-MESSENGER-RNA; EXONIC SPLICING ENHANCERS; HYALURONAN SYNTHASES; INTRACELLULAR HYALURONAN; 5'-SPLICE-SITE SELECTION; SR PROTEINS; CANCER; EXPRESSION; TRANSFORMATION; MECHANISM AB The hyaluronan synthase 1 (HAS1) gene encodes a plasma membrane protein that synthesizes hyaluronan, an extracellular matrix molecule. Previously, in patients with Waldenstrom's macroglobulinemia (WM), we detected upregulation of HAS1 transcripts and identified aberrant splice variants of this gene. Aberrant splicing of HAS1 results from activation of cryptic splice sites. In turn, activation of cryptic donor and acceptor splice sites can be promoted by mutations occurring upstream of these sites and/or at the branch point of slicing. We measured the frequency of the HAS1 833A/G polymorphism (ie, single-nucleotide polymorphism; SNP) in patients with WM and healthy donors. Additionally, HAS1 gene expression was evaluated in the same group of patients. Our observations so far suggest that HAS1 833A/G Ills contribute to aberrant splicing of this gene; this idea is supported by the fact that MING SIP is located on an exonic splicing enhancer motif. Based on the results obtained thus far, we speculate that individuals with HAS1 833G/G genotype are predisposed toward aberrant HAS1 splicing and expression of HAS1 variants, resulting in an enhanced risk of developing WM. Study of a larger group of patients and healthy donors is needed to confirm these speculations and to evaluate the prognostic significance of these findings. C1 Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Alberta, Dept Oncol, Edmonton, AB, Canada. Univ Alberta, Dept Med, Edmonton, AB, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pilarski, LM (reprint author), Cross Canc Inst, 11560 Univ Ave, Edmonton, AB T6G 1Z2, Canada. EM lpilarsk@ualberta.ca FU NCI NIH HHS [CA 80963] NR 34 TC 11 Z9 12 U1 0 U2 0 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD MAR PY 2005 VL 5 IS 4 BP 253 EP 256 DI 10.3816/CLM.2005.n.010 PG 4 WC Oncology SC Oncology GA 981HK UT WOS:000233078100010 PM 15794859 ER PT J AU Treon, SP Hunter, Z Branagan, AR AF Treon, SP Hunter, Z Branagan, AR TI CHOP plus Rituximab therapy in Waldenstrom's macroglobulinemia SO CLINICAL LYMPHOMA LA English DT Article; Proceedings Paper CT 3rd International Workshop on Waldenstroms Macroglobulinemia CY OCT 07-10, 2004 CL Paris, FRANCE SP Int Waldenstroms Macroglobulinemia Fdn, Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia DE CD20; CHOP-R; febrile neutropenia; flow cytometry; Hematocrit; nucleoside analogue ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; ANTI-CD20 MONOCLONAL-ANTIBODY; LYMPHOMA; EXPRESSION AB Recently, a consensus panel of experts recommended that patients with Waldenstrom's macroglobulinemia (WM) who are candidates for future autologous transplantation should have limited alkylator or nucleoside analogue exposure due to potential stem cell harm. Cyclophosphamide/doxorubicin/vincristine/prednisone/rituximab (CHOP-R) is a stem cell-sparing regimen that has been extensively evaluated in patients without WM or non-Hodgkin's lymphoma. As such, we analyzed the outcome of 13 patients with WM who received CHOP-R at our institution. Patients had a median age of 54 years and a median of 1 previous therapy. Ten of 13 patients (77%) had relapsed (n = 3) or refractory (n = 7) disease. Eight and 6 patients had previously received fludarabine and rituximab, respectively. Intended therapy consisted of 6 cycles of standard-dose CHOP and 6 infusions of rituximab (375 mg/m(2)). Three patients received additional rituximab as maintenance therapy. Median immunoglobulin M and serum viscosity for all patients decreased from 5230 mg/dL to 1690 mg/dL (P <= 0.001) and from 2.9 cP to 1.6 cP (P = 0.01), respectively, and the median hematocrit level rose from 30.5% to 39.3% (P <= 0.001). Clinical responses were as follows: 3 complete responses unconfirmed, 8 partial responses, 1 minor response. At a median follow-up of 9 months (range, 6 to > 37 months), 10 of the 11 patients who had a major response remained in remission. Therapy was well tolerated for most patients. Two patients had febrile neutropenia with documented bacteremia and recovered without complications. Circulating effector cell levels were also evaluated in 6 patients before and after CHOP-R, because rituximab activity is mediated in part by antibody-dependent cell-mediated cytotoxicity activity. No significant change in CD3(+), CD4(+) CD8(+). and CD16(+)/CD56(+) effector cell levels occurred following CHOP-R as assessed by multicolor flow cytometry. C1 Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, LG 102,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Branagan, Andrew/0000-0002-3868-9267 NR 24 TC 34 Z9 35 U1 0 U2 0 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD MAR PY 2005 VL 5 IS 4 BP 273 EP 277 DI 10.3816/CLM.2005.n.015 PG 5 WC Oncology SC Oncology GA 981HK UT WOS:000233078100015 PM 15794864 ER PT J AU Cox, E Brush, KA Martin, AI AF Cox, E Brush, KA Martin, AI TI The CNS and evidence-based practice: Implementing a perioperative beta-blockade therapy program SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2005 VL 19 IS 2 BP 71 EP 71 DI 10.1097/00002800-200503000-00019 PG 1 WC Nursing SC Nursing GA 036OT UT WOS:000237085000020 ER PT J AU Gonzalez, CE Haldeman, SM Silva, JH AF Gonzalez, CE Haldeman, SM Silva, JH TI Job sharing in the CNS role: Who does what? SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2005 VL 19 IS 2 BP 73 EP 73 DI 10.1097/00002800-200503000-00030 PG 1 WC Nursing SC Nursing GA 036OT UT WOS:000237085000031 ER PT J AU Haldeman, S Gonzalez, C Clerpal, CL Cox, E Silva, JH AF Haldeman, S Gonzalez, C Clerpal, CL Cox, E Silva, JH TI Who develops clinical staff? SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2005 VL 19 IS 2 BP 74 EP 74 DI 10.1097/00002800-200503000-00032 PG 1 WC Nursing SC Nursing GA 036OT UT WOS:000237085000033 ER PT J AU Jeffries, M Gavaghan, S AF Jeffries, M Gavaghan, S TI CNS intervention to improve care of the respiratory-compromised patient SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2005 VL 19 IS 2 BP 76 EP 76 PG 1 WC Nursing SC Nursing GA 036OT UT WOS:000237085000041 ER PT J AU Jeffries, M AF Jeffries, M TI CNS development of a patient-teaching plan for tracheostomy patients SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2005 VL 19 IS 2 BP 76 EP 76 PG 1 WC Nursing SC Nursing GA 036OT UT WOS:000237085000040 ER PT J AU Johnson, E Griffith, CA AF Johnson, E Griffith, CA TI Clinical issue analysis: Finding evidence for the use of air-eliminating filters on intravenous lines in adult patients with patent foramen ovale SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2005 VL 19 IS 2 BP 76 EP 76 DI 10.1097/00002800-200503000-00041 PG 1 WC Nursing SC Nursing GA 036OT UT WOS:000237085000042 ER PT J AU Martin, A Spiro, M Evangelista, S AF Martin, A Spiro, M Evangelista, S TI Trauma nursing SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract 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 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2005 VL 19 IS 2 BP 77 EP 78 DI 10.1097/00002800-200503000-00045 PG 2 WC Nursing SC Nursing GA 036OT UT WOS:000237085000046 ER PT J AU Mankin, HJ Hornicek, FJ Raskin, KA AF Mankin, HJ Hornicek, FJ Raskin, KA TI Infection in massive bone allografts SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TERM-FOLLOW-UP; PROXIMAL TIBIA; LIMB SALVAGE; ENDOPROSTHETIC RECONSTRUCTION; OSTEOCHONDRAL ALLOGRAFTS; IMMUNOLOGICAL RESPONSES; SURVIVORSHIP ANALYSIS; MALIGNANT-TUMORS; HUMAN RECIPIENTS; TRANSPLANTATION AB We studied a series of 945 patients who received cadaveric allografts implanted for nonpelvic bone or soft tissue tumor lesions since 1971. We specifically were interested in the role of infection in the graft process, and, more specifically its history, frequency, and affect on outcome. Primary infections (not related to reoperations for nonunions or fractures of the graft) occurred in 75 patients (7.9%), and an additional 46 patients had infections related to reoperations, increasing the total number of patients with infections to 121 (12.8%). The highest frequency of infection occurred in patients with soft tissue tumors, radiated sites, Musculoskeletal Tumor Society Stage IIB tumors, or surgeries consisting of an allograft arthrodesis. Most of the infected grafts failed; however, none of the patients died. One patient had hepatitis C develop, and one patient became HIV positive after receiving the virus from a blood transfusion. A comparison with other series of surgically treated patients, including those receiving metallic devices, suggests that the infection rate may be related to the surgery or the graft's immunologic resistance, rather than the graft. The problem of infection is a major issue for tumor surgeons. Suggestions regarding how to decrease the frequency of this complication are presented. C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. EM hmankin@partners.org NR 84 TC 94 Z9 103 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2005 IS 432 BP 210 EP 216 DI 10.1097/01.blo.0000150371.77314.52 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 903HU UT WOS:000227417400028 PM 15738824 ER PT J AU Safren, SA AF Safren, SA TI Affirmative, evidence-based, and ethically sound psychotherapy with lesbian, gay, and bisexual clients SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE psychotherapy; gay, lesbian, and bisexual issues ID SEXUAL ORIENTATION; MEN AB Writing from the perspective of heterosexual therapists treating lesbian, gay, and bisexual (LGB) individuals, Eubanks-Carter, Burckell, and Goldfried (this issue) provide important information on how to enhance therapeutic effectiveness with this population. Their manuscript is an example of a refreshing departure from historical views of homosexuality as a pathological psychological condition and from work that supports using therapy to change sexual orientation. Eubanks-Carter et al. document significant improvements both in the provision of psychotherapy, the view of LGB individuals from the mental health field, and the view of LGB individuals from the community. Despite these improvements, continued progress is still needed. The present commentary points to several areas where the science and practice of clinical psychology can further progress regarding the care of LGB clients. This includes improving systems in training and institutions that employ psychologists where bias or discrimination may exist and reducing biased language in psychological research that implies pathology towards homosexual sexual orientations when homosexuality is not a pathological condition. It also includes reducing or eliminating psychological harm that can be caused by psychological interventions that attempt to change sexual orientation by further restricting these practices. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA USA. RP Safren, SA (reprint author), WACC 815,15 Pk Man St, Boston, MA 02114 USA. EM ssafren@partners.org RI George, Sarah/D-4782-2012 NR 22 TC 3 Z9 3 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SPR PY 2005 VL 12 IS 1 BP 29 EP 32 DI 10.1093/clipsy/bpi003 PG 4 WC Psychology, Clinical SC Psychology GA 897CZ UT WOS:000226982900004 ER PT J AU Otto, MW Smits, JAJ Reese, HE AF Otto, MW Smits, JAJ Reese, HE TI Combined psychotherapy and pharmacotherapy for mood and anxiety disorders in adults: Review and analysis SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE combination treatment; cognitive-behavior therapy; psychopharmacology; anxiety disorders; depression; bipolar disorder ID COGNITIVE-BEHAVIOR THERAPY; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; MAJOR DEPRESSIVE DISORDER; FAMILY-FOCUSED TREATMENT; LONG-TERM TREATMENT; PANIC DISORDER; BIPOLAR DISORDER; SOCIAL PHOBIA; FOLLOW-UP AB Studies suggest a complex relationship between cognitive-behavior therapy (CBT) and pharmacotherapy for the combined treatment of mood disorders and anxiety disorders. Combined treatment for depression may have beneficial effects when applied to patients with chronic depression and in cases to prevent relapse. In bipolar disorder there is evidence for a strong effect of psychosocial treatment on the course of the disorder. In the anxiety disorders, there are some benefits in the short term, but combined treatment may limit the maintenance of treatment gains offered by CBT alone. Combined treatment should not be considered the default treatment for mood and anxiety disorders, with the possible exception of bipolar disorder. Instead, decisions whether combined treatment is worth the added cost and effort should be made in relation to the disorder under treatment, the level of severity or chronicity, and the stage of treatment (e.g., acute vs. relapse prevention). C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM mwotto@bu.edu RI Smits, Jasper/A-4350-2008; OI Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 NR 93 TC 103 Z9 103 U1 10 U2 24 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SPR PY 2005 VL 12 IS 1 BP 72 EP 86 DI 10.1093/clipsy/bpi009 PG 15 WC Psychology, Clinical SC Psychology GA 897CZ UT WOS:000226982900010 ER PT J AU Restrepo, MI Anzueto, A AF Restrepo, MI Anzueto, A TI Antimicrobial treatment of community-acquired pneumonia SO CLINICS IN CHEST MEDICINE LA English DT Article ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; RESISTANT STREPTOCOCCUS-PNEUMONIAE; INITIAL EMPIRIC THERAPY; HOSPITALIZED-PATIENTS; PROGNOSTIC-FACTORS; ELDERLY-PATIENTS; MEDICAL OUTCOMES; PSEUDOMONAS-AERUGINOSA; BACTERIAL PNEUMONIA; SEVERITY CRITERIA AB Community-acquired pneumonia (CAP) is a clinical diagnosis that has a significant impact on health care management around the world. Early clinical suspicion and prompt empiric antimicrobial therapies are mandatory in patients with CAP. This article provides a review of recent studies and guidelines addressing antimicrobial therapy for hospitalized patients with CAP. C1 Univ Texas, Hlth Sci Ctr, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Anzueto, A (reprint author), Univ Texas, Hlth Sci Ctr, Div Pulm & Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu NR 75 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD MAR PY 2005 VL 26 IS 1 BP 65 EP + DI 10.1016/j.ccm.2004.10.006 PG 11 WC Respiratory System SC Respiratory System GA 913RD UT WOS:000228169800009 PM 15802167 ER PT J AU Henderson, DC AF Henderson, David C. TI Metabolic Differences of Antipsychotics Among the Races SO CNS SPECTRUMS LA English DT Article AB As the United States population continues to grow and diversify, physicians must be equipped to treat patients of different races and ethnicities. Current data suggest that certain ethnic minority groups may be predisposed to a variety of clinical conditions, including obesity, diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease. Furthermore, as physicians begin to turn more frequently to atypical antipsychotics in psychiatric illness, they face a growing concern regarding the development of metabolic side effects, especially in a US population that is gradually becoming more obese from a demographic standpoint. In addition, certain ethnic groups may be more susceptible to these metabolic effects. The metabolic side effects induced by the atypical antipsychotics vary greatly, with the newer agents generally displaying fewer and less severe side effects, indicating that the particular agent chosen is of critical importance. A risk/benefit assessment, taking into consideration any genetic predisposition, preexisting risk factors, and the side-effect profile of the specific agent, is paramount to the successful management of these patients. The ultimate goal is careful consideration of possible metabolic side effects in patients taking atypical antipsychotics, in order to avoid serious consequences. CNS Spectr. 2005; 10(3 Suppl 2):13-20 C1 [Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Saniford St,2nd Floor, Boston, MA 02114 USA. EM dchenderson@partners.org NR 44 TC 3 Z9 3 U1 3 U2 3 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAR PY 2005 VL 10 IS 3 BP 13 EP 20 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V04RI UT WOS:000207075100004 ER PT J AU Kosslyn, SM Thompson, WL Sukel, KE Alpert, NM AF Kosslyn, SM Thompson, WL Sukel, KE Alpert, NM TI Two types of image generation: Evidence from PET SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; COORDINATE SPATIAL RELATIONS; MENTAL-IMAGERY; VISUAL-IMAGERY; CEREBRAL HEMISPHERES; FUNCTIONAL NEUROANATOMY; COMPUTATIONAL ANALYSIS; IDENTIFYING OBJECTS; WORKING-MEMORY; NEURAL SYSTEMS AB Is there more than one method whereby people can generate visual mental images? Participants generated images after learning patterns in two ways. In one condition, they memorized descriptions of how segments are arranged to form patterns; in another, they memorized segments and mentally amalgamated them into patterns. In both conditions, identical stimuli cued them to form images while brain activation was monitored using PET. Comparison of the two imagery conditions revealed different activation between hemispheres when images were formed after patterns were learned by mentally combining segments versus when images were formed from stored verbal descriptions. Thus, images can be generated in at least two ways. However, this laterality difference was subtle; the majority of brain areas were activated in common across conditions. This overall similarity is counter to what would be expected if image generation is simply perceptual exploration in the absence of appropriate stimuli, as is posited by perceptual activity theory. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kosslyn, SM (reprint author), Harvard Univ, Dept Psychol, 832 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM smk@wjh.harvard.edu FU NIMH NIH HHS [R01 MH60734] NR 66 TC 15 Z9 19 U1 1 U2 3 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD MAR PY 2005 VL 5 IS 1 BP 41 EP 53 DI 10.3758/CABN.5.1.41 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 976FG UT WOS:000232717600005 PM 15913007 ER PT J AU Kong, H Wang, CM Kwong, K Vangel, M Chua, E Gollub, R AF Kong, H Wang, CM Kwong, K Vangel, M Chua, E Gollub, R TI The neural substrate of arithmetic operations and procedure complexity SO COGNITIVE BRAIN RESEARCH LA English DT Article DE mental arithmetic; calculation; fMRI; brain network ID ANTERIOR CINGULATE CORTEX; MENTAL CALCULATION; PARIETAL CORTEX; WORKING-MEMORY; CORTICAL ACTIVATION; FUNCTIONAL MRI; FACTS; ORGANIZATION; AREAS; SUBTRACTION AB Recent functional neuroimaging studies have begun to clarify how the human brain performs the everyday activities that require mental calculation. We used fMRI to test the hypotheses that there are specific neural networks dedicated to performing an arithmetic operation (e.g. (+) or -) and to performing processes that support more complex calculations. We found that the right inferior parietal lobule, left precuneus and left superior parietal gyrus are relatively specific for performing subtraction; and bilateral medial frontal/cingulate cortex are relatively specific for supporting arithmetic procedure complexity. We also found that greater difficulty level was associated with activation in a brain network including left inferior intraparietal sulcus, left inferior frontal gyrus and bilateral cingulate. Our results suggest that the network activated by the simplest calculation serves as a common basis, to which more regions are recruited for more difficult problems or different arithmetic operations. (c) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. MIT, MGH, HMS, Athinoala A Martios Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Kong, H (reprint author), Psychiat Neuroimaging, Bldg 149,13th St,Suite 9109, Charlestown, MA 02129 USA. EM kongj@nmr.mgh.harvard.edu RI Chua, Elizabeth/B-3770-2010; OI Gollub, Randy L./0000-0002-9434-4044 NR 41 TC 37 Z9 37 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD MAR PY 2005 VL 22 IS 3 BP 397 EP 405 DI 10.1016/j.cogbrainres.2004.09.011 PG 9 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 907BW UT WOS:000227691000008 ER PT J AU Davis, LL Rush, JA Wisniewski, SR Rice, K Cassano, P Jewell, ME Biggs, MM Shores-Wilson, K Balasubramani, GK Husain, MM Quitkin, FM McGrath, PJ AF Davis, LL Rush, JA Wisniewski, SR Rice, K Cassano, P Jewell, ME Biggs, MM Shores-Wilson, K Balasubramani, GK Husain, MM Quitkin, FM McGrath, PJ TI Substance use disorder comorbidity in major depressive disorder: An exploratory analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DIAGNOSTIC SCREENING QUESTIONNAIRE; ALCOHOL-USE DISORDERS; ILLNESS RATING-SCALE; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; GENDER DIFFERENCES; QUICK INVENTORY; SYMPTOMATOLOGY; OUTPATIENTS; RELIABILITY AB Patients with major depressive disorder (MDD) often present with concurrent substance use disorders (SUD) involving alcohol and/or illicit drugs. This analysis compares the depressive symptomatic presentation and a range of clinical and demographic features of patients with MDD and concurrent SUD symptoms vs those without SUD symptoms, to clarify how these two differ and to determine whether concurrent SUD symptoms may alter the clinical presentation of MDD. The first 1500 outpatients with nonpsychotic MDD enrolled in the Sequenced Treatment Alternatives to Relieve Depression study were divided into those with and without concurrent SUD symptoms as ascertained by a self-report instrument, the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Of the 1484 cases with completed baseline PDSQ, 28% (n = 419) of patients with MDD were found to endorse symptoms consistent with current SUD. Patients with symptoms consistent with SUD were more likely to be men (P < .0001), to be either divorced or never married (P < .018), to have a younger age of onset of depression ( P = .014), and to have a higher rate of previous suicide attempts ( P = .014) than those without SUD symptoms. Patients with major depressive disorder who have symptoms consistent with SUD endorsed greater functional impairment attributable to their illness than those without concurrent SUD symptoms (P = .0111). The presence of SUD symptoms did not alter the overall depressive symptom pattern of presentation, except that the dual-diagnosed patients had higher levels of hypersomnia (P = .006), anxious mood (P = .047), and suicidal ideation (P = .036) compared to those without SUD symptoms. In conclusion, gender, marital status, age of onset of major depression, functional impairment, and suicide risk factors differ in depressed patients with concurrent SUD symptoms compared to those without SUD comorbidity. (c) 2005 Elsevier Inc. All rights reserved. C1 VA Med Ctr, Tuscaloosa, AL 35404 USA. Univ Alabama Birmingham, Birmingham, AL 35494 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Davis, LL (reprint author), VA Med Ctr, Tuscaloosa, AL 35404 USA. EM lori.davis@med.va.gov RI Biggs, Dr. Melanie/C-1468-2010; Cassano, Paolo/I-6959-2012; McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01MH90003] NR 32 TC 42 Z9 43 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAR-APR PY 2005 VL 46 IS 2 BP 81 EP 89 DI 10.1016/j.comppsych.2004.07.025 PG 9 WC Psychiatry SC Psychiatry GA 906SE UT WOS:000227662200001 PM 15723023 ER PT J AU Pekow, C AF Pekow, C TI Defining, measuring, and interpreting stress in laboratory animals SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID SPRAGUE-DAWLEY RATS; COMMON PROCEDURES; BEHAVIORAL-RESPONSES; PARAMETERS; MICE AB One basis of scientific research with animal subjects is consistency of subject physiology, physical parameters, and behavior. Ideally, selected experimental variables account for primary differences measured between test and control groups. One intangible variable to control is stress experienced by the animals. In common parlance, the word stress is often used to indicate a negative experience. However, stress is not inherently bad, and a stress response should not be assumed to indicate an experience of distress or pain. This paper examines ways in which research animal stress may be defined, measured, and interpreted. C1 Vet Affairs Puget Sound Hlth Care Syst, Vet Med Unit, Seattle, WA 98108 USA. RP Pekow, C (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Vet Med Unit, Res 151-L,1660 S Columbian Way, Seattle, WA 98108 USA. NR 43 TC 10 Z9 10 U1 0 U2 5 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAR PY 2005 VL 44 IS 2 BP 41 EP 45 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 947GG UT WOS:000230630800007 PM 15773775 ER PT J AU Jain, M Pfister, O Hajjar, RJ Liao, RL AF Jain, M Pfister, O Hajjar, RJ Liao, RL TI Mesenchymal stem cells in the infarcted heart SO CORONARY ARTERY DISEASE LA English DT Review DE mesenchymal stem cells; myocardial regeneration; myocardial infarction; cell therapy ID HUMAN BONE-MARROW; STROMAL CELLS; IN-VITRO; PROGENITOR CELLS; MYOCARDIAL-INFARCTION; CARDIOMYOCYTE PHENOTYPE; PRECURSOR CELLS; TRANSPLANTATION; REGENERATION; ENGRAFTMENT AB A loss of functional cardiomyocytes forms the cellular basis of cardiac dysfunction and heart failure. Stem cell based repletion of scarred myocardial tissue and regeneration of cardiomyocytes have been proposed as a potential treatment of ventricular dysfunction. In this review, we provide an overview of recent studies utilizing mesenchymal stem cells in cardiac regeneration and post-myocardial infarct therapy. (c) 2005 Lippincott Williams A Wilkins. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Med, Boston, MA 02118 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. RP Liao, RL (reprint author), Boston Univ, Sch Med, Cardiac Muscle Res Lab, 650 Albany St,X-26, Boston, MA 02118 USA. EM rliao@bu.edu FU NHLBI NIH HHS [HL073756, HL71763, HL57263, HL071775, HL067297] NR 46 TC 21 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD MAR PY 2005 VL 16 IS 2 BP 93 EP 97 DI 10.1097/00019501-200503000-00003 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 910NT UT WOS:000227939200003 PM 15735401 ER PT J AU Zhu, XS Bernecker, OY Manohar, NS Hajjar, RJ Hellman, J Ichinose, F Valdivia, HH Schmidt, U AF Zhu, XS Bernecker, OY Manohar, NS Hajjar, RJ Hellman, J Ichinose, F Valdivia, HH Schmidt, U TI Increased leakage of sarcoplasmic reticulum Ca2+ contributes to abnormal myocyte Ca2+ handling and shortening in sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE sepsis; Ca2+ sparks; myocyte shortening; calcium ID RYANODINE RECEPTOR; VENTRICULAR MYOCYTES; RELEASE CHANNEL; HEART-FAILURE; MYOCARDIAL DYSFUNCTION; CELLULAR MECHANISMS; CALCIUM-RELEASE; SEPTIC SHOCK; GUINEA-PIGS; MUSCLE AB Objective: Changes in cardiac function due to sepsis have been widely reported. However, the underlying mechanisms remain poorly understood. In the mammalian heart, myocyte function and intracellular calcium homeostasis are closely coupled. In this study we tested the hypothesis that alterations in cardiac calcium homeostasis due to sepsis underlie the observed myocyte dysfunction. Design: Randomized prospective animal study. Setting. Research laboratory. Subjects: Male Sprague-Dawley rats weighing 250-275 g. Interventions: We induced sepsis by cecal ligation and puncture in the rat, which mimics the type of infection caused by perforation of the intestine in humans. Measurements and Results. Forty-eight hours after cecal ligation and puncture, isolated cardiac ventricular cardiomyocytes demonstrated a 57% decreased peak systolic [Ca2+]. The time constant of the Ca2+ transient increased 71% and 57% in myocytes obtained 24 hrs and 48 hrs after cecal ligation and puncture, respectively. The average shortening of cardiomyocytes 48 hrs after cecal ligation and puncture was significantly decreased. To investigate the cellular mechanisms of altered Ca2+ transients and myocyte shortening, we measured Ca2+ sparks, the spontaneous local Ca2+ release events in cardiomyocytes at resting states. The Ca2+ spark frequency progressively increased in myocytes 24 hrs and 48 hrs after cecal ligation and puncture. The total activity of sparks also increased compared with sham-operated animals. The overall leakage of sarcoplasmic reticulum Ca2+ in resting states was increased in sepsis and resulted in reduced sarcoplasmic reticulum Ca2+ content. Conclusions. Abnormal Ca2+ leakage from the sarcoplasmic reticulum contributes significantly to the depressed myocyte shortening in sepsis. In the future, modalities that prevent this Ca2+ leakage may prove beneficial in the treatment of sepsis induced myocyte shortening. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. Univ Wisconsin, Sch Med, Dept Physiol, Madison, WI 53706 USA. RP Schmidt, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM uschmidt@partners.org FU NHLBI NIH HHS [HL 57623, 5 K08 HL 69778, HL 071763] NR 28 TC 35 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2005 VL 33 IS 3 BP 598 EP 604 DI 10.1097/01.ccm.0000152223.27176.A6 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 907CD UT WOS:000227691800018 PM 15753753 ER PT J AU Hinton, DE Nguyen, L Tran, M Quinn, S AF Hinton, DE Nguyen, L Tran, M Quinn, S TI Weak kidney and panic attacks in a traumatized Vietnamese male SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article ID DISORDER; PREVALENCE C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 15 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD MAR PY 2005 VL 29 IS 1 BP 125 EP 135 DI 10.1007/s11013-005-4626-5 PG 11 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 951WS UT WOS:000230963700007 PM 16108206 ER PT J AU Cummings, DE Foster-Schubert, KE Overduin, J AF Cummings, DE Foster-Schubert, KE Overduin, J TI Ghrelin and energy balance: Focus on current controversies SO CURRENT DRUG TARGETS LA English DT Review DE Ghrelin; obesity; body-weight regulation; energy homeostasis; weight loss; cachexia; gastric motility; insulin secretion; meals ID GROWTH-HORMONE SECRETAGOGUE; PRADER-WILLI-SYNDROME; INSULIN-INDUCED HYPOGLYCEMIA; AGOUTI-RELATED PROTEIN; RAT ARCUATE NUCLEUS; DES-ACYL GHRELIN; GASTRIC-ACID-SECRETION; BODY-MASS INDEX; CEREBROSPINAL-FLUID GHRELIN; GLUCAGON-LIKE PEPTIDE-1 AB Ghrelin is an enteric peptide that is the only known circulating appetite stimulant. This feature of the hormone has garnered widespread attention, as reflected by more than 1000 scientific papers featuring ghrelin that have been published since the first reports of its orexigenic actions, approximately four years ago. In this review, we discuss data that support roles for ghrelin in the short-term regulation of pre-meal hunger and meal initiation, functioning as a unique orexigenic counterpart to short-acting gastrointestinal satiation factors, such as cholecystokinin (CCK). We also highlight evidence indicating that ghrelin satisfies recognized criteria to be viewed as a participant in long-term body-weight regulation - a potential anabolic counterpart to the traditional adiposity hormones, leptin and insulin. We then discuss the following controversial questions in ghrelin research and offer our opinions regarding these debates. (1) Is ghrelin synthesized within the brain? (2) How does ghrelin increase food intake? (3) Does des-acyl ghrelin have a physiologic function? (4) Are there receptors for ghrelin other than GHS-R1a? (5) Does ghrelin regulate insulin secretion? (6) Does ghrelin regulate gastrointestinal motility? (7) Can ghrelin or ghrelin-receptor agonists be used to treat wasting conditions? Finally, we offer a speculative model of ghrelin as a thrifty gene product that evolved to help animals consume and store fat well, thereby increasing their chances of survival during times of famine. We suggest that ghrelin is a "saginary" hormone, from the Latin, saginare, which means, "to fatten". C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111-Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu FU NIDDK NIH HHS [P01 DK 68384, R01 DK 61516, U01 DK 66568] NR 270 TC 127 Z9 133 U1 1 U2 16 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD MAR PY 2005 VL 6 IS 2 BP 153 EP 169 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 903JR UT WOS:000227422600003 PM 15777186 ER PT J AU Hezel, AF Bardeesy, N Maser, RS AF Hezel, AF Bardeesy, N Maser, RS TI Telomere induced senescence: End game signaling SO CURRENT MOLECULAR MEDICINE LA English DT Review DE telomeres; telomerase; senescence; genomic instability ID HUMAN CELLULAR SENESCENCE; HUMAN CANCER-CELLS; DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; REPLICATIVE SENESCENCE; RNA COMPONENT; CHROMOSOMAL INSTABILITY; DEFICIENT MICE; CORD BLOOD; LIFE-SPAN AB The telomere-based model of cell aging has proven to among been among the most enduring hypotheses in cell biology. This model, suggesting that the gradual loss of telomere sequences during the proliferation of cultured human somatic cells imposes a barrier on cellular replicative potential, has been strongly supported by recent genetic and biochemical studies. In addition, evidence implicating telomere dynamics in organismal ageing and cancer progression in vivo suggest that such a process is likely to have considerable physiological relevance in homeostasis and disease. What is the sensing mechanism for shortened telomeres and what is the molecular basis for the ensuing checkpoint response? Moreover, what is the outcome when such failsafe mechanisms are lost? Here we will review the signaling pathways that are induced by alterations in telomere length and integrity and illustrate how these processes provoke downstream effects on cell proliferation and survival. In addition, we discuss how the telomere-induced pathways intersect with the DNA damage response and document how the failure in either process results in unrestrained chromosomal instability. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Maser, RS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. EM Richard_Maser@dfci.harvard.edu RI Maser, Richard/B-2970-2012 NR 89 TC 11 Z9 15 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAR PY 2005 VL 5 IS 2 BP 145 EP 152 DI 10.2174/1566524053586563 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 916JH UT WOS:000228380700003 PM 15974867 ER PT J AU Greenberg, RA AF Greenberg, RA TI Telomeres, crisis and cancer SO CURRENT MOLECULAR MEDICINE LA English DT Review ID MISMATCH REPAIR; HUMAN-CELLS; CHROMOSOMAL INSTABILITY; HUMAN FIBROBLASTS; IMMORTAL CELLS; DEFICIENT MICE; RNA COMPONENT; TUMOR-CELLS; LIFE-SPAN; DYSFUNCTION AB Eukaryotic chromosomes terminate in specialized nucleic acid-protein complexes known as telomeres. Disruption of telomere structure by erosion of telomeric DNA or loss of telomere binding protein function activates a signal transduction program that closely resembles the cellular responses generated upon DNA damage. Telomere dysfunction in turn induces a permanent proliferation arrest known as senescence. Senescence is postulated to perform a tumor suppressor function by limiting cellular proliferative capacity, thus imposing a barrier to cellular immortalization. Genetic or epigenetic silencing of components of the DNA damage pathway, allows cells to proliferate beyond senescence limits. However, these cells eventually reach a stage of extreme telomere dysfunction known as crisis that is characterized by cell death and the concomitant appearance of cytogenetic abnormalities. Telomeric crisis produces significant chromosomal instability, a hallmark of human cancer, and may thus be relevant to carcinogenesis by increasing the occurrence of genetic alterations that would favor neoplastic transformation. The following review examines the relationship of telomere function during crisis in accelerating chromosomal instability and cancer. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Greenberg, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM rgreenberg@partners.org NR 50 TC 30 Z9 33 U1 2 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAR PY 2005 VL 5 IS 2 BP 213 EP 218 DI 10.2174/1566524053586590 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 916JH UT WOS:000228380700011 PM 15974875 ER PT J AU Hahn, WC AF Hahn, WC TI Telomere and telomerase dynamics in human cells SO CURRENT MOLECULAR MEDICINE LA English DT Review ID HEMATOPOIETIC STEM-CELLS; REPLICATIVE LIFE-SPAN; HUMAN TUMOR-CELLS; DYSKERATOSIS-CONGENITA; CATALYTIC SUBUNIT; HOMOLOGOUS RECOMBINATION; MAMMALIAN TELOMERES; ECTOPIC EXPRESSION; WERNER-SYNDROME; IMMORTAL CELLS AB Accumulating evidence now implicates telomeres and telomerase as critical regulators genomic stability and replicative lifespan in mammalian cells. Disruption of telomere maintenance and/or telomerase expression contributes to the etiology of some degenerative diseases and may participate in the process of aging. Although telomere dysfunction and aberrant telomerase expression clearly play important roles in cancer development, the contribution of telomere biology to cancer is complex and involves both positive and negative influences on tumor development. Indeed, recent work from several laboratories suggests additional roles for telomeres and telomerase in both normal and malignant, physiology. Understanding the complexity of telomere biology will provide further insights into chromosome biology in both normal and malignant cells. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@DFCI.Harvard.edu FU NCI NIH HHS [K01 CA94223]; NIA NIH HHS [R01 AG023145] NR 69 TC 26 Z9 32 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAR PY 2005 VL 5 IS 2 BP 227 EP 231 DI 10.2174/1566524053586572 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 916JH UT WOS:000228380700013 PM 15974877 ER PT J AU Roy, CN Andrews, NC AF Roy, CN Andrews, NC TI Anemia of inflammation: the hepcidin link SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE anemia; hemochromatosis; hepcidin; inflammation; iron recycling ID ANTIMICROBIAL PEPTIDE HEPCIDIN; IRON REGULATORY PEPTIDE; JUVENILE HEMOCHROMATOSIS; CHRONIC DISEASE; EXPRESSION; LIVER; GENE; MICE; HFE; OVERLOAD AB Purpose of review The anemia of inflammation has been associated for nearly two decades with elevated cytokine levels, but the primary mediator of this condition was unknown. Recently hepcidin antimicrobial peptide has emerged as the hormone that links the type 11 acute phase response to iron handling and erythropoiesis. Recent findings Hepcidin antimicrobial peptide likely modulates iron transport from macrophages and enterocytes to red blood cell precursors as a consequence of its interaction with SLC40A1/ferroportin, the only known transporter that facilitates iron egress. Insights into the regulation of hepcidin antimicrobial peptide expression by known iron metabolic proteins such as HFE, hemojuvelin, and transferrin receptor 2 are expanding the understanding of the genetic circuitry that controls iron absorption and utilization. Summary Increasingly, experiments suggest the hepatocyte is not just the iron storage depot but is the 'command central' for the maintenance of iron homeostasis. It receives multiple signals related to iron balance and responds via transcriptional control of hepcidin antimicrobial peptide. C1 Childrens Hosp, Karp Family Res Labs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Childrens Hosp, Karp Family Res Labs, RM 8-125, Boston, MA 02115 USA. EM nancy_andrews@hms.harvard.edu OI Andrews, Nancy/0000-0003-0243-4462 NR 36 TC 106 Z9 112 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2005 VL 12 IS 2 BP 107 EP 111 DI 10.1097/00062752-200503000-00001 PG 5 WC Hematology SC Hematology GA 947PP UT WOS:000230658800001 PM 15725899 ER PT J AU Cunningham, MJ Nathan, DG AF Cunningham, MJ Nathan, DG TI New developments in iron chelators SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE chelation; iron; thalassemia ID BETA-THALASSEMIA MAJOR; LABILE PLASMA IRON; DUAL-ENERGY CT; MAGNETIC-RESONANCE; COMBINED THERAPY; LOADED PATIENTS; REDOX ACTIVITY; ORAL CHELATOR; HEART-CELLS; DEFEROXAMINE AB Purpose of review For three decades, deferoxamine has been the only approved iron chelator. This drug has an extremely short-half life and is not orally absorbed; thus, a search has been ongoing for alternative chelators with less onerous delivery. Recently, several oral iron chelators and variations of deferoxamine to prolong the half-life have been developed. These and the methods of monitoring iron overload are the subjects of this review. Recent findings New chelators, combinations of chelators and regimens for known chelators and their safety and efficacy are being studied in important preclinical and clinical trials. Summary The are and clinical outcomes of patients with thalassemia and other iron-overload disorders may be markedly improved by recent discoveries and novel approaches to chelation therapy. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Thalassemia Program, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Div Hematol Oncol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Harvard Univ, Sch Med, 300 Longwood Ave,Fegan 703, Boston, MA 02115 USA. EM Melody.Cunningham@childrens.harvard.edu NR 49 TC 28 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2005 VL 12 IS 2 BP 129 EP 134 DI 10.1097/01.moh.0000152631.63469.07 PG 6 WC Hematology SC Hematology GA 947PP UT WOS:000230658800005 PM 15725903 ER PT J AU Kubicki, M McCarley, RW Shenton, ME AF Kubicki, M McCarley, RW Shenton, ME TI Evidence for white matter abnormalities in schizophrenia SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE brain abnormalities; diffusion tensor imaging; fractional anisotropy; interstitial neurons; magnetic resonance imaging; magnetic transfer imaging; myelin oligodendrocytes; schizophrenia; white matter ID EARLY-ONSET SCHIZOPHRENIA; VOXEL-BASED MORPHOMETRY; PREFRONTAL CORTEX; 1ST-EPISODE SCHIZOPHRENIA; DIFFUSION ANISOTROPY; INTERSTITIAL NEURONS; UNCINATE FASCICULUS; BRAIN ABNORMALITIES; MONOZYGOTIC TWINS; NEGATIVE SYMPTOMS AB Purpose of review The purpose of this review is to highlight important recent imaging, histological, and genetic findings relevant to white matter abnormalities in schizophrenia. It is cast within the 1 context of research findings conducted over the last 5 years, where we analyze their importance in understanding schizophrenia, as well as discuss future directions for research. Recent findings White matter abnormalities have long been hypothesized in schizophrenia, although only recently has it become possible to investigate them more closely, This has come about as a result of advances in neuroirnaging, including new imaging techniques sensitive to white matter structure, as well as advances in computer science, with new analysis techniques making it possible to evaluate several interconnected brain regions at a time. Postmortem studies, with advances such as fluoroscopy and electron microscopy, have also led to quantifying populations of different brain cells, including myelin-forming oligodendrocytes. Moreover, molecular studies enable examination of immunoreactivity of proteins that are responsible for building myelin sheaths. Additionally, microarray genetic studies allow us to investigate myelin-related genes in schizophrenia. Taken together, these technological advances bring us closer to understanding white matter pathology in schizophrenia. Summary Advances in new imaging techniques likely account for the renewed interest in investigating white matter abnormalities in schizophrenia, with over 30 new articles published on this topic in the last 12 months, compared with 11 the year before. We review recent imaging, histological, and genetic findings that suggest white matter abnormalities in schizophrenia. C1 Harvard Univ, VA Boston Healthcare Syst, Sch Med, Clin Neurosci Div,Lab Neurosci,Dept Psychiat, Brockton, MA 02401 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Surg Planning Lab,MRI Div, Boston, MA 02115 USA. RP Shenton, ME (reprint author), Harvard Univ, Sch Med, Dept Psychiat 116A, VA Boston Healthcare Syst,Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM martha_shenton@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [K02 MH001110, K02 MH001110-10, R01 MH040799, R03 MH068464] NR 71 TC 74 Z9 75 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAR PY 2005 VL 18 IS 2 BP 121 EP 134 DI 10.1097/00001504-200503000-00004 PG 14 WC Psychiatry SC Psychiatry GA 931QA UT WOS:000229498800003 PM 16639164 ER PT J AU Krishnan, LL Suarez-Almazor, ME AF Krishnan, LL Suarez-Almazor, ME TI Evidence-based rheumatology practice SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE evidence based medicine; professional practice; rheumatic diseases; rheumatology ID RANDOMIZED CONTROLLED-TRIALS; QUALITY INDICATOR SET; OF-THE-LITERATURE; ARTHRITIS CARE; KNEE OSTEOARTHRITIS; HYALURONIC-ACID; METAANALYSIS; METHOTREXATE; INJECTIONS; EFFICACY AB Purpose of review This review is intended to update readers on recent developments in the evidence-based practice of rheumatology. Recent findings Several new or updated evidence-based practice guidelines have recently emerged. In addition, a large body of evidence upon which to base practice has been addressed in the many systematic reviews and meta-analyses that have been newly published, including nine new or updated Cochrane reviews. Several studies have also investigated adherence to practice guidelines, interventions to improve clinical practice, and quality of care in the field of rheumatology in the past year. Summary Evidence-based rheumatology is an ongoing effort, with continuing revision and update of recommendations. It may currently be used to address a wide variety of clinical questions. The initiatives on practice based research to establish quality indicators and identify areas where rheumatology practice can be enhanced are a welcome addition to health services research in this field. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP Suarez-Almazor, ME (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mes@bcm.tmc.edu NR 59 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAR PY 2005 VL 17 IS 2 BP 117 EP 123 PG 7 WC Rheumatology SC Rheumatology GA 912LH UT WOS:000228079200001 PM 15711221 ER PT J AU Choi, HK AF Choi, HK TI Dietary risk factors for rheumatic diseases SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE diet; epidemiology; nutrition; rheumatic; risk factors ID FISH-OIL SUPPLEMENTATION; SERUM URIC-ACID; ADENINE-NUCLEOTIDE TURNOVER; IOWA WOMENS HEALTH; DOUBLE-BLIND; FATTY-ACIDS; MEDITERRANEAN DIET; OLIVE OIL; OMEGA-3-FATTY-ACID SUPPLEMENTATION; INFLAMMATORY POLYARTHRITIS AB Purpose of review Recent scientific data illuminate the dietary link to rheumatic disorders. This review summarizes recently published articles on the dietary link to rheumatoid arthritis, gout, and osteoarthritis. Recent findings A prospective study suggests that higher intakes of meat and total protein as well as lower intakes of fruit, vegetables, and vitamin-C are associated with an increased risk of inflammatory polyarthritis or rheumatoid arthritis. Several studies suggest that the Mediterranean-type diet or its main components may have protective effects on the development or severity of rheumatoid arthritis. a recent prospective study investigated several purported dietary factors for gout and confirmed some of the long-standing suspicions (red meats, seafood, beer, and liquor), exonerated others (total protein, wine, and purine-rich vegetables), and also identified potentially new protective factors (dairy products). Recent double-blind, randomized placebo-controlled studies suggest that antioxidant vitamins (vitamin E, vitamin C, beta-carotene, and retinol) do not halt the progression of symptomatic knee osteoarthritis, as was previously suggested. Summary Because diet is an unavoidable universal exposure for people, even a small effect that can be achieved by dietary manipulation may produce a large impact on the population's health. As the evidence on the role of dietary factors in rheumatic disorders grows it becomes increasingly important for clinicians and investigators in the field of rheumatology to familiarize themselves with the relevant data and appropriately apply them to clinical and public health practice. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Rheumatol Unit, Boston, MA 02114 USA. RP Choi, HK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Rheumatol Unit, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org NR 61 TC 18 Z9 23 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAR PY 2005 VL 17 IS 2 BP 141 EP 146 DI 10.1097/01.cco.0000152664.87204.3c PG 6 WC Rheumatology SC Rheumatology GA 912LH UT WOS:000228079200005 PM 15711225 ER PT J AU Tannous, ZS Avram, MM Zembowicz, A Mihm, MC Liteplo, M Kwan, T Olbricht, SM AF Tannous, ZS Avram, MM Zembowicz, A Mihm, MC Liteplo, M Kwan, T Olbricht, SM TI Treatment of synchronous mucinous carcinoma and endocrine mucin-producing sweat gland carcinoma with Mohs' micrographic surgery SO DERMATOLOGIC SURGERY LA English DT Editorial Material AB BACKGROUND. Endocrine mucin-producing sweat gland carcinoma is a very rare cutaneous tumor that has been reported only in three patients previously. We report a case of an endocrine mucin-producing sweat gland carcinoma associated with mucinous carcinoma treated by Mobs' micrographic surgery. OBJECTIVE. The purpose of this report is to test the utility of Mobs' micrographic surgery in the treatment of mucinous carcinomata. METHODS. A 79-year-old female with a 2-year history of four lesions of biopsy-proven endocrine mucin-producing sweat gland carcinomas and mucinous carcinoma was treated with Mobs' micrographic surgery. RESULTS. Three of the lesions were completely cleared by Mohs' micrographic surgery. The fourth lesion, in the right lateral canthus, was not cleared by the Mohs' technique because of its location within the orbit and the difficulty of retraction of the globe for appropriate visualization and excision. The patient underwent wide excision of the remaining orbital tumor and reconstruction, which was successfully accomplished. The patient did not experience a recurrence in any of her four lesions over a 2-year follow-up period. CONCLUSION. Mohs' micrographic surgery is an appropriate treatment for mucinous carcinomata, including endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma. C1 Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dermatopathol Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Hosp, Dept Dermatol, Boston, MA USA. Lahey Clin Fdn, Dept Pathol, Burlington, MA USA. Lahey Clin Fdn, Dept Dermatol, Burlington, MA USA. RP Tannous, ZS (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Bartlett 616,55 Fruit St, Boston, MA 02114 USA. EM ztannous@partners.org NR 3 TC 16 Z9 16 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 2005 VL 31 IS 3 BP 364 EP 367 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 902KH UT WOS:000227354100022 PM 15841644 ER PT J AU Houghton, L Lindon, C Morgan, BA AF Houghton, L Lindon, C Morgan, BA TI The ectodysplasin pathway in feather tract development SO DEVELOPMENT LA English DT Article DE ectodysplasin; Edar; Edaradd; feather bud; pattern formation ID ECTODERMAL DYSPLASIA; MORPHOGENESIS; DIFFERENTIATION; APPENDAGES; PATTERNS; HOMOLOG; BMPS; EDAR; GENE AB The ectodysplasin pathway, comprising the ligand ectodysplasin, its receptor Edar and a dedicated death domain adaptor protein Edaradd, plays an important role in epidermal organ formation in mammals. Mutations in the genes encoding these proteins cause dysplasia or absence of teeth, sweat glands and hair follicles. However, the relative position of this pathway in the regulatory hierarchy directing follicle formation remains unclear. In this work, the chicken orthologs of Eda, Edar and Edaradd were cloned to exploit the temporal precision of the feather tract system in order to study the role of the ectodysplasin pathway. We find that these genes are expressed in a similar pattern during feather and hair development, with the notable difference that the ligand Eda, which is expressed in the epidermis of the mouse, is expressed in the dermis of the feather tract. Contrary to conclusions reached from the analysis of mutant mice, we find that localization of Edar expression to the nascent placode is coincident or subsequent to the local expression of other markers of placodal differentiation, and not an upstream event in tract patterning. Furthermore, forced expression of BMP and activated beta-catenin demonstrate that local expression of Edar is dictated by the interaction between these two pathways. These results suggest that activation of the ectodysplasin pathway may be permissive for activating signals to overcome signals that inhibit placode formation, but the function of this pathway in the specification of follicle initiation lies downstream of other patterning events. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th Str, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu FU NICHD NIH HHS [HD38465] NR 23 TC 31 Z9 31 U1 0 U2 7 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 MAR PY 2005 VL 132 IS 5 BP 863 EP 872 DI 10.1242/dev.01651 PG 10 WC Developmental Biology SC Developmental Biology GA 912QC UT WOS:000228093300002 PM 15673574 ER PT J AU Gekas, C Dieterlen-Lievre, F Orkin, SH Mikkola, HKA AF Gekas, C Dieterlen-Lievre, F Orkin, SH Mikkola, HKA TI The placenta is a niche for hematopoietic stem cells SO DEVELOPMENTAL CELL LA English DT Article ID CULTURE-INITIATING CELLS; UMBILICAL-CORD BLOOD; MURINE YOLK-SAC; MOUSE EMBRYO; BONE-MARROW; GROWTH-FACTOR; PRIMITIVE STREAK; AGM REGION; IN-VIVO; LIVER AB The hematopoietic system develops during embryogenesis at temporally and anatomically restricted sites. The anatomical origin of definitive HSCs is not fully resolved, and little is known about how the different fetal hematopoietic microenvironments direct HSC development. Here, we show that the mouse placenta functions as a hematopoietic organ that harbors a large pool of pluripotent HSCs during midge-station. The onset of HSC activity in the placenta parallels that of the AGM (aorta-gonad-mesonephros) region starting at E10.5-E11.0. However, the placental HSC pool expands until E12.5-E13.5 and contains > 15-fold more HSCs than the AGM. The expansion of the CD34(+)c-kit(+) HSC pool in the placenta occurs prior to and during the initial expansion of HSCs in the fetal liver. Importantly, the placental HSC pool is not explained by rare circulating HSCs, which appear later. These data support an important, but unappreciated, role for the placenta in establishing the mammalian definitive hematopoietic system. 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. CNRS, Lab Embryol Cellulaire & Mol, F-94736 Nogent Sur Marne, France. Coll France, F-94736 Nogent Sur Marne, France. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu RI Gekas, Christos/M-3209-2015 OI Gekas, Christos/0000-0002-3429-4145 NR 54 TC 326 Z9 339 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR PY 2005 VL 8 IS 3 BP 365 EP 375 DI 10.1016/j.devcel.2004.12.016 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 906CK UT WOS:000227617900011 PM 15737932 ER PT J AU Veraksa, A Bauer, A Artavanis-Tsakonas, S AF Veraksa, A Bauer, A Artavanis-Tsakonas, S TI Analyzing protein complexes in Drosophila with tandem affinity purification-mass spectrometry SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Notch; Drosophila; mass spectrometry; protein complexes ID NOTCH; MASTERMIND; TRANSCRIPTION; RECEPTOR; ENCODES; PATHWAY; MEMBER; CELLS; DELTA; LOCI AB We describe the application of tandem affinity purification-mass spectrometry (TAP-MS) to the study of protein complexes in Drosophila. We have constructed vectors for inducible expression of TAP-tagged fusion proteins in Drosophila cultured cells and in vivo. Using these vectors, we tagged, as a paradigm, several components of the Notch signaling pathway, isolated protein complexes containing the baits and associated proteins from cells and embryos, and identified the subunits by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Several known interactions involving Notch pathway elements were confirmed, and many novel potential interactions were uncovered. For some of the novel associations, we validated the interaction genetically and biochemically. We conclude that TAP, in combination with MS, can be used as an effective method for the studies of the Drosophila proteome. (C) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Cell Biol, Charlestown, MA 02129 USA. Cellzome AG, Heidelberg, Germany. Coll France, Paris, France. RP Veraksa, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Cell Biol, Bldg 149,13th St,7th Floor, Charlestown, MA 02129 USA. EM veraksa@helix.mgh.harvard.edu FU NCI NIH HHS [CA098402]; NIGMS NIH HHS [GM62931]; NINDS NIH HHS [NS26084] NR 26 TC 71 Z9 78 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAR PY 2005 VL 232 IS 3 BP 827 EP 834 DI 10.1002/dvdy.20272 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 902BD UT WOS:000227325300027 PM 15704125 ER PT J AU Jimenez-Chillaron, JC Hernandez-Valencia, M Reamer, C Fisher, S Joszi, A Hirshman, M Oge, A Walrond, S Przybyla, R Boozer, C Goodyear, LJ Patti, ME AF Jimenez-Chillaron, JC Hernandez-Valencia, M Reamer, C Fisher, S Joszi, A Hirshman, M Oge, A Walrond, S Przybyla, R Boozer, C Goodyear, LJ Patti, ME TI beta-cell secretory dysfunction in the pathogenesis of low birth weight-associated diabetes - A murine model SO DIABETES LA English DT Article ID INTRAUTERINE GROWTH-RETARDATION; INSULIN-RESISTANCE SYNDROME; FOR-GESTATIONAL-AGE; CATCH-UP GROWTH; HEPATIC GLUCOSE OUTPUT; THRIFTY PHENOTYPE; SKELETAL-MUSCLE; ISOLATED ISLETS; HEXOKINASE-I; FETAL-RAT AB Low birth weight (LBW) is an important risk factor for type 2 diabetes. We have developed a mouse model of LBW resulting from undernutrition during pregnancy. Restriction of maternal food intake from day 12.5 to 18.5 of pregnancy results in a 23% decrease in birth weight (P < 0.001), with normalization after birth. However, offspring of undernutrition pregnancies develop progressive, severe glucose intolerance by 6 months. To identify early defects that are responsible for this phenotype, we analyzed mice of undernutrition pregnancies at age 2 months, before the onset of glucose intolerance. Fed insulin levels were 1.7-fold higher in mice of undernutrition pregnancies (P = 0.01 vs. controls). However, insulin sensitivity was normal in mice of undernutrition pregnancies, with normal insulin tolerance, insulin-stimulated glucose disposal, and isolated muscle and adipose glucose uptake. Although insulin clearance was mildly impaired in mice of undernutrition pregnancies, the major metabolic phenotype in young mice of undernutrition pregnancies was dysregulation of insulin secretion. Despite normal P-cell mass, islets from normoglycemic mice of undernutrition pregnancies showed basal hypersecretion of insulin, complete lack of responsiveness to glucose, and a 2.5fold increase in hexokinase activity. Taken together, these data suggest that, at least in mice, primary beta-cell dysfunction may play a significant role in the pathogenesis of LBW-associated type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Patti, ME (reprint author), Room 640 C,1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu RI Jimenez-Chillaron, Josep/L-5854-2015 FU NIDDK NIH HHS [DK02526, P30 DK26687] NR 50 TC 67 Z9 69 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2005 VL 54 IS 3 BP 702 EP 711 DI 10.2337/diabetes.54.3.702 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903KB UT WOS:000227423600015 PM 15734846 ER PT J AU Zhang, XB Gaspard, JP Mizukami, Y Li, JN Graeme-Cook, F Chung, DC AF Zhang, XB Gaspard, JP Mizukami, Y Li, JN Graeme-Cook, F Chung, DC TI Overexpression of cyclin D1 in pancreatic beta-cells in vivo results in islet hyperplasia without hypoglycemia SO DIABETES LA English DT Article ID TRANSGENIC MICE; BREAST-CANCER; RAT PANCREAS; GROWTH; PROLIFERATION; EXPRESSION; DIFFERENTIATION; PROTEIN; MASS; P53 AB Cyclin D1 can stimulate proliferation by driving cells from the G1 into the S-phase of the mammalian cell cycle. Previous animal studies have implicated the G1-S transition as a key regulatory checkpoint governing the proliferation of pancreatic islet cells. We expressed cyclin DI in the beta-cells of mice and islet hyperplasia developed in a time-dependent manner. The hyperplastic P-cells exhibited higher rates of proliferation. However, blood glucose levels in fasting as well as nonfasting conditions remained normal. Furthermore, glucose tolerance tests demonstrated nearly normal responses, and diabetes did not develop in any of the animals. No islet cell tumors were observed, even among animals >2 years of age. Under our experimental conditions, the proliferative stimulus provided by cyclin D1 is not tumorigenic, does not result in diabetes, and does not result in hypoglycemia. Cyclin DI may thus be considered a potential candidate to augment the P-cell population ex vivo as a prelude to islet transplantation for diabetes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,70 Blossom St, Boston, MA 02114 USA. EM chung.daniel@mgh.harvard.edu NR 34 TC 49 Z9 55 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2005 VL 54 IS 3 BP 712 EP 719 DI 10.2337/diabetes.54.3.712 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903KB UT WOS:000227423600016 PM 15734847 ER PT J AU Winckler, W Graham, RR de Bakker, PIW Sun, M Almgren, P Tuomi, T Gaudet, D Hudson, TJ Ardlie, KG Daly, MJ Hirschhorn, JN Groop, L Altshuler, D AF Winckler, W Graham, RR de Bakker, PIW Sun, M Almgren, P Tuomi, T Gaudet, D Hudson, TJ Ardlie, KG Daly, MJ Hirschhorn, JN Groop, L Altshuler, D TI Association testing of variants in the hepatocyte nuclear factor 4 alpha gene with risk of type 2 diabetes in 7,883 people SO DIABETES LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; NUCLEAR FACTOR-4-ALPHA GENE; GENOME-WIDE SEARCH; SUSCEPTIBILITY LOCUS; CHROMOSOME 20Q; SIB PAIRS; UPSTREAM PROMOTER; HNF-4-ALPHA GENE; COMPLEX TRAITS; ALPHA-GENE AB Two recent publications reported association of common polymorphisms in the P2 promoter of hepatocyte nuclear factor 4alpha (HNF4alpha) (the MODY1 gene) with risk for type 2 diabetes. We attempted to reproduce this putative association by genotyping 11 single nucleotide polymorphism (SNPs) spanning the HNF4a coding region and the P2 promoter in >3,400 patients and control subjects from Sweden, Finland, and Canada. One SNP that was consistently associated in the two previous reports (rs1884613, in the P2 promoter region) also trended in the same direction in our sample, albeit with a lower estimated odds ratio (OR) of 1.11 (P = 0.05, one-tailed). We genotyped this SNP (rs1884613) in an additional 4,400 subjects from North America and Poland. In this sample, the association was not confirmed and trended in the opposite direction (OR 0.88). Meta-analysis of our combined sample of 7,883 people (three times larger than the two initial reports combined) yielded an OR of 0.97 (P = 0.27). Finally, we provide an updated analysis of haplotype structure in the region to guide any further investigation of common variation in HNF4alpha. Although our combined results fail to replicate the previously reported association of common variants in HNF4alpha with risk for type 2 diabetes, we cannot exclude an effect smaller than that originally proposed, heterogeneity among samples, variation in as-yet-unmeasured genotypic or environmental modifiers, or true association secondary to linkage disequilibrium (LD) with as-yet-undiscovered variant(s) in the region. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Lund Univ, Univ Hosp, MAS, Dept Endocrinol, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Folkhalsan Genet Inst,Folkhalsan Res Ctr, FIN-00014 Helsinki, Finland. Univ Helsinki, Res Program Mol Med, FIN-00014 Helsinki, Finland. Univ Montreal, Chicoutimi Hosp, Community Genom Ctr, Montreal, PQ, Canada. McGill Univ, Montreal, PQ, Canada. Genome Quebec Innovat Ctr, Montreal, PQ, Canada. Genom Collaborat Inc, Cambridge, MA USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Groop, L (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM leif.groop@endo.mas.lu.se; 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 NR 44 TC 58 Z9 58 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2005 VL 54 IS 3 BP 886 EP 892 DI 10.2337/diabetes.54.3.886 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903KB UT WOS:000227423600038 PM 15734869 ER PT J AU Wexler, DJ Grant, RW Meigs, JB Nathan, DM Cagliero, E AF Wexler, DJ Grant, RW Meigs, JB Nathan, DM Cagliero, E TI Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; PRIMARY-CARE; MORTALITY; CHOLESTEROL; MELLITUS; GENDER; WOMEN; MANAGEMENT AB OBJECTIVE - Diabetes eliminates the protective effect of female sex on the risk of coronary heart disease (CHD). We assessed sex differences in the treatment of CHD risk factors among patients with diabetes. RESEARCH DESIGN AND METHODS - A cross-sectional analysis included 3,849 patients with diabetes treated in five academic internal medicine practices from 2000 to 2003. Outcomes were stratified by the presence of CHD and included adjusted odds ratios (AORS) that women (relative to men) were treated with hypoglycemic, antihypertensive, lipid-lowering medications or aspirin (if indicated) and AORs of reaching target HbA(1c), blood pressure, or lipid levels. RESULTS- Women were less likely than men to have HbA(1c) < 7% (without CHD: AOR 0.84 [95% Cl 0.75-0.95], P = 0.005; with CHD: 0.63 [0.53-0.75], P < 0.0001). Women without CHD were less likely than men to be treated with lipid-lowering medication (0.82 [0.71-0.96], P = 0.01) or, when treated, to have LDL cholesterol levels < 100 mg/dl (0.75 [0,62-0.93], P = 0.004) and were less likely than men to be prescribed aspirin (0.63 [0.55-0.72], P < 0.0001) Women with diabetes and CHD were less likely than men to be prescribed aspirin (0.70 [0.600-83], P < 0.0001) or, when treated for hypertension or hyperlipidemia, were less likely to have blood pressure levels < 130/80 mmHg (0.75 [0.69-0.82], P < 0.0001) or LDL cholesterol levels < 100 mg/dl (0.80 [0.68-0.94], P = 0.006). CONCLUSIONS - Women with diabetes received less treatment for man), modifiable CHD risk factors than diabetic men. More aggressive treatment of CHD risk factors in this population offers a specific target for improvement in diabetes care. C1 Massachusetts Gen Hosp, Diabet Unit, Ctr Diabet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, Diabet Unit, Ctr Diabet, 55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452, K23 DK080228, K23 DK067452-02] NR 41 TC 153 Z9 155 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2005 VL 28 IS 3 BP 514 EP 520 DI 10.2337/diacare.28.3.514 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903ME UT WOS:000227429200002 PM 15735180 ER PT J AU Polonsky, WH Fisher, L Earles, J Dudl, RJ Lees, J Mullan, J Jackson, RA AF Polonsky, WH Fisher, L Earles, J Dudl, RJ Lees, J Mullan, J Jackson, RA TI Assessing psychosocial distress in diabetes - Development of the Diabetes Distress Scale SO DIABETES CARE LA English DT Article ID QUALITY-OF-LIFE; PROBLEM AREAS; MARITAL RELATIONSHIP; INTENSIVE TREATMENT; GLYCEMIC CONTROL; QUESTIONNAIRE; INDIVIDUALS; VALIDITY AB OBJECTIVE - The purpose of this Study was to describe the development of the Diabetes Distress Scale (DDS), a new instrument for the assessment of diabetes-related emotional distress, based on four independent patient samples. RESEARCH DESIGN AND METHODS - in consultation with patients and professionals from multiple disciplines, a preliminary scale of 28 items was developed, based a priori on four distress-related domains: emotional burden subscale, physician-related distress subscale, regimen-related distress subscale, and diabetes-related interpersonal distress. The new instrument was included in a larger battery of questionnaires used in diabetes studies at four diverse Sites: waiting room at a primary care clinic (n = 200), waiting room at a diabetes specialty clinic (n = 179), a diabetes management Study program (n = 167), and an ongoing diabetes management progam (n = 158). RESULTS - Exploratory factor analyses revealed four factors consistent across sites (involving 17 of the 28 items) that matched the critical content domains identified earlier. The correlation between the 28-item and 17-item scales was very high (r = 0.99). The mean correlation between the 17-item total score (DDS) and the four subscales was high (r = 0.82), but the pattern of interscale correlations suggested that the subscales, although not totally independent, tapped into relatively different areas of diabetes-related distress. Internal reliability of the DDS and the four subscales was adequate (alpha > 0.87), and validity coefficients yielded significant linkages with the Center for Epidemiological Studies Depression Scale, meal planning, exercise, and total cholesterol. Insulin users evidenced the highest mean DDS total scores, whereas diet-controlled subjects displayed the lowest scores (P < 0.001). CONCLUSIONS - The DDS has a consistent, generalizable factor structure and good internal reliability and validity across four different clinical sites. The new instrument may serve as a valuable measure of diabetes-related emotional distress for use in research and clinical practice. C1 Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. Tripler Army Med Ctr, Honolulu, HI 96859 USA. Kaiser Permanente, San Diego, CA USA. USN, Med Ctr, San Diego, CA 92152 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Polonsky, WH (reprint author), CDE,POB 2148, Del Mar, CA 92014 USA. EM whpolonsky@aol.com NR 19 TC 275 Z9 286 U1 5 U2 37 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2005 VL 28 IS 3 BP 626 EP 631 DI 10.2337/diacare.28.3.626 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903ME UT WOS:000227429200021 PM 15735199 ER PT J AU Gunton, JE Cheung, NW Hitchman, R Hams, G O'Sullivan, C Foster-Powell, KE McElduff, A AF Gunton, JE Cheung, NW Hitchman, R Hams, G O'Sullivan, C Foster-Powell, KE McElduff, A TI Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile - A randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance SO DIABETES CARE LA English DT Article ID TOTAL PARENTERAL-NUTRITION; DEFICIENCY C1 Kahn Lab, Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Royal N Shore Hosp, Dept Endocrinol, St Leonards, NSW 2065, Australia. Westmead & Nepean Hosp, Western Sydney Area Hlth Serv, Dept Diabet & Endocrinol, Sydney, NSW, Australia. Royal N Shore Hosp, Pacific Lab Med Serv, Sydney, NSW, Australia. RP Gunton, JE (reprint author), Kahn Lab, Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Level 6,1 Joslin Pl, Boston, MA 02215 USA. EM jenny.gunton@joslin.harvard.edu NR 7 TC 45 Z9 46 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2005 VL 28 IS 3 BP 712 EP 713 DI 10.2337/diacare.28.3.712 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903ME UT WOS:000227429200036 PM 15735214 ER PT J AU Kemmis, K Stuber, D AF Kemmis, K Stuber, D TI Diabetes and osteoporotic fractures - The role of the diabetes educator SO DIABETES EDUCATOR LA English DT Editorial Material ID BONE-MINERAL DENSITY; OLDER WOMEN; RISK-FACTORS; MELLITUS; TYPE-1; FALLS; METAANALYSIS; OSTEOPENIA; NEUROPATHY; PEOPLE AB The purpose of this article is to present information that will assist the diabetes educator in screening patients with diabetes for risk of osteoporosis and fracture, to offer appropriate treatment options for patients, and to identify potential referrals to other providers for patients with diabetes and increased risk of fracture. C1 SUNY Syracuse, Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY 13202 USA. RP Kemmis, K (reprint author), SUNY Syracuse, Upstate Med Univ, Joslin Diabet Ctr, 90 Presidential Plaza, Syracuse, NY 13202 USA. EM kemmisk@upstate.edu NR 28 TC 3 Z9 4 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAR-APR PY 2005 VL 31 IS 2 BP 187 EP + DI 10.1177/045721705275409 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 910NQ UT WOS:000227938900003 PM 15797848 ER PT J AU Kearns, JW Kemmis, K Ploutz-Snyder, R Weinstock, RS AF Kearns, JW Kemmis, K Ploutz-Snyder, R Weinstock, RS TI It's mine - Initiating treatment success - My individualized nutrition and exercise plan SO DIABETES EDUCATOR LA English DT Editorial Material AB The authors' class structure incorporates individual meal and exercise planning in the group setting. This study was conducted to (1) determine if class participants can create their own meal and exercise plans, (2) determine if class participants feel they will be able to adhere to their meal and exercise plans, and (3) assess adherence to the plans over time. Subjects were recruited from the classes offered at the Joslin Diabetes Center. Following completion of class, patients completed the evaluation questionnaire! Two and 6 months later, study participants received follow-up questionnaires by phone or mail. Among respondents, 63% were able to determine their own carbohydrate goals, with 95.9% indicating they could adhere to the plan, and 82.8% felt the plan would be easier than previous ones. At 2 and 6 months, respectively, 89% and 92% of the participants felt they were following the meal plan either some or most of the time. One hundred percent of the respondents were able to determine their own exercise plan, with 98% indicating they could adhere to the plan, and 85.7% felt the new plan would be easier than previous ones. At 2 and 6 months, respectively, 70% and 73% felt they were following their exercise plan either some or most of the time. Individualized meal and exercise plans can be successfully created in a group setting. C1 Syracuse Univ, Hlth Care Ctr, Joslin Diabet Ctr, Syracuse, NY 13202 USA. SUNY Syracuse, Upstate Med Ctr, Syracuse, NY USA. RP Kearns, JW (reprint author), Syracuse Univ, Hlth Care Ctr, Joslin Diabet Ctr, 90 Presidential Plaza, Syracuse, NY 13202 USA. EM kearnsj@upstate.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAR-APR PY 2005 VL 31 IS 2 BP 199 EP + DI 10.1177/0145721705275453 PG 5 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 910NQ UT WOS:000227938900004 PM 15797849 ER PT J AU Rutkove, SB Chapman, KM Acosta, JA Larrabee, JE AF Rutkove, SB Chapman, KM Acosta, JA Larrabee, JE TI Foot temperature in diabetic polyneuropathy: innocent bystander or unrecognized accomplice? SO DIABETIC MEDICINE LA English DT Review DE diabetic polyneuropathy; temperature; pathogenesis; pain; ischaemia ID FREEZING COLD INJURY; CELL-MEDIATED-IMMUNITY; SENSORY NERVE-FIBERS; PROTEIN-KINASE-C; AUTONOMIC NEUROPATHY; BLOOD-FLOW; AXONAL-TRANSPORT; ANTEROGRADE TRANSPORT; PERIPHERAL NEUROPATHY; TISSUE OXYGENATION AB Aim To explore mechanisms by which temperature could influence the pathogenesis and symptoms of diabetic polyneuropathy. Methods We conducted a literature review attempting to identify mechanisms by which diabetic polyneuropathy could be affected by temperature. Results Cooling can theoretically hasten the progression of diabetic polyneuropathy through several different mechanisms. Specifically, cooling can enhance neuronal ischaemia, increase formation of reactive oxygen species, slow axonal transport, increase protein kinase C activity, and interfere with immune function. Short-term temperature fluctuations (both warming and cooling) can initiate and exacerbate neuropathic pain by causing neuronal hyperexcitability and functional deafferentation. Although normal fluctuations of distal extremity temperature may be sufficient for these effects, impaired thermoregulation may make the distal extremities more susceptible to temperature extremes. Eventually, a 'vicious cycle' may ensue, resulting in neuronal deterioration with further disruption of temperature regulation. Limited epidemiological data suggest a higher prevalence of diabetic polyneuropathy in populations living in colder locations, supporting our hypothesis. Conclusions Variations in foot temperature may play an important but as yet unrecognized role in the development and symptoms of diabetic polyneuropathy. Further basic and clinical research exploring this concept could help elucidate the natural history of diabetic polyneuropathy and lead to novel therapeutic strategies. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Rutkove, SB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, 330 Brookline Ave,TCC-810, Boston, MA 02215 USA. EM srutkove@bidmc.harvard.edu NR 96 TC 6 Z9 7 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAR PY 2005 VL 22 IS 3 BP 231 EP 238 DI 10.1111/j.1464-5491.2005.01486.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 897PD UT WOS:000227016200001 PM 15717867 ER PT J AU Kobayashi, T Kronenberg, H AF Kobayashi, T Kronenberg, H TI Minireview: Transcriptional regulation in development of bone SO ENDOCRINOLOGY LA English DT Review ID GROWTH-FACTOR-BETA; NF-KAPPA-B; CHONDROCYTE-SPECIFIC ENHANCER; COLONY-STIMULATING FACTOR; ACID-PHOSPHATASE GENE; LACKING C-FOS; OSTEOBLAST DIFFERENTIATION; CARTILAGE FORMATION; INDIAN-HEDGEHOG; SKELETAL DEVELOPMENT AB Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kronenberg, H (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. NR 90 TC 106 Z9 112 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2005 VL 146 IS 3 BP 1012 EP 1017 DI 10.1210/en.2004-1343 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 897WC UT WOS:000227035400009 PM 15604211 ER PT J AU Habener, JF Kemp, DM Thomas, MK AF Habener, JF Kemp, DM Thomas, MK TI Minireview: Transcriptional regulation in pancreatic development SO ENDOCRINOLOGY LA English DT Review ID INSULIN GENE-TRANSCRIPTION; CELL-SPECIFIC TRANSCRIPTION; TYPE-2 DIABETES-MELLITUS; LOOP-HELIX PROTEIN; FACTOR-I IPF-1; BETA-CELLS; ENDOCRINE-CELLS; SECRETORY RESPONSES; BINDING-ACTIVITY; HOMEOBOX FACTOR AB Considerable progress has been made in the understanding of the sequential activation of signal transduction pathways and the expression of transcription factors during pancreas development. Much of this understanding has been obtained by analyses of the phenotypes of mice in which the expression of key genes has been disrupted (knockout mice). Knockout of the genes for Pdx1, Hlxb9, Isl1, or Hex results in an arrest of pancreas development at a very early stage (embryonic d 8-9). Disruption of genes encoding components of the Notch signaling pathway, e.g. Hes1 or neurogenin-3, abrogates development of the endocrine pancreas ( islets of Langerhans). Disruption of transcription factor genes expressed more downstream in the developmental cascade (Beta2/NeuroD, Pax4, NKx2.2, and Nkx6.1) curtails the formation of insulin-producing beta-cells. An understanding of the importance of transcription factor genes during pancreas development has provided insights into the pathogenesis of diabetes, in which the mass of insulin-producing beta-cells is reduced. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Novartis Inst BioMed Res, Cambridge, MA 02139 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK-55365, DK-02476] NR 116 TC 255 Z9 275 U1 1 U2 28 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2005 VL 146 IS 3 BP 1025 EP 1034 DI 10.1210/en.2004-1576 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 897WC UT WOS:000227035400011 PM 15604203 ER PT J AU Ray, KK Morrow, DA Gibson, CM Murphy, S Antman, EM Braunwald, E AF Ray, KK Morrow, DA Gibson, CM Murphy, S Antman, EM Braunwald, E CA ENTIRE TIMI 23 Study Grp TI Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome - An ENTIRE-TIMI 23 substudy SO EUROPEAN HEART JOURNAL LA English DT Article DE vWF; TIMI flow grade; corrected TIMI frame count; ST elevation myocardial; infarction; endothelial activation ID VON-WILLEBRAND-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; ENDOTHELIAL-CELL FUNCTION; MOLECULAR-WEIGHT HEPARIN; UNSTABLE ANGINA; VONWILLEBRAND-FACTOR; UNFRACTIONATED HEPARIN; ADHESION MOLECULES; ARTERY-DISEASE; BONE-MARROW AB Aims Prior studies suggest that acute coronary syndromes (ACSs) are associated with endothetial activation and that this is of prognostic significance. We hypothesized that endothetial activation, as measured by a rise in von Willebrand Factor (&UDelta; vWF), was influenced by the thrombolysis in myocardial infarction flow grade (TFG), the corrected TIM1 frame count (CTFC) and the choice of anticoagutant therapy after fibrinolysis in ST elevation myocardial infarction (STEMI). Methods and results Data were drawn from the enoxaparin and tenecteplase tissue plasminogen activator (TNK-tpa) with or without GPIIb/IIIa inhibitor as the reperfusion strategy in the STEMI trial (ENTIRE-TIMI 23). Three hundred and fourteen patients had serial measurements of vWF (baseline and 48-72 h) and angiographic data available. TFG < 3 (P = 0.0042) or CTFC &GE; 40 at 60 min (P = 0.0035) were associated with a higher &UDelta; vWF. &UDelta; vWF &GE; 75th percentile was associated with a higher incidence of death or myocardial infarction (MI) at 30 days, compared with < 75th percentile (11.2 vs. 4.1%, P = 0.027). Enoxaparin independently reduced the &UDelta; vWF (P = 0.019) and also the composite of death or MI (OR 0.33, 95% CI 0.12-0.91, P = 0.03) compared with unfractionated heparin. Conclusion In STEMI treated by fibrinolysis, coronary flow at 60 min and choice of adjunctive anticoagulant appear to be independent determinants of &UDelta; vWF. Enoxaparin is independently associated with a reduction in &UDelta; vWF and a reduction in death or MI. The clinical benefits of enoxaparin as an adjunctive treatment in STEMI may be mediated in part by a reduction in vWF release. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. RP Ray, KK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM kkray@partners.org NR 41 TC 34 Z9 42 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAR PY 2005 VL 26 IS 5 BP 440 EP 446 DI 10.1093/eurheartj/ehi104 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 923ER UT WOS:000228892500007 PM 15673542 ER PT J AU Becker, V Ketteler, R Schilling, M Baumann, U Heinrich, AC Ruan, W Sengupta, D Langosch, D Smith, JC Klingmuller, U AF Becker, V Ketteler, R Schilling, M Baumann, U Heinrich, AC Ruan, W Sengupta, D Langosch, D Smith, JC Klingmuller, U TI A single residue in the transmembrane domain of the erythropoietin receptor regulates lipid raft localization and signal amplification SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Deutsche-Gesellschaft-fur-Zellbiologie CY MAR 16-19, 2005 CL Heidelberg, GERMANY SP Deutsch Gesell Zellbiol C1 German Canc Res Ctr, D-6900 Heidelberg, Germany. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Tech Univ Munich, D-8000 Munich, Germany. IWR, Heidelberg, Germany. EM v.becker@dkfz-heidelberg.de RI smith, jeremy/B-7287-2012; Klingmuller, Ursula/G-8477-2013 OI smith, jeremy/0000-0002-2978-3227; Klingmuller, Ursula/0000-0001-9845-3099 NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2005 VL 84 SU 55 BP 45 EP 45 PG 1 WC Cell Biology SC Cell Biology GA 918FM UT WOS:000228527700081 ER PT J AU Lin, B Masland, RH AF Lin, B Masland, RH TI S(y)naptic contacts between an identified type of ON cone bipolar cell and ganglion cells in the mouse retina SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE bipolar cell; ganglion cell; GFP; retina; synaptic contacts ID STARBURST AMACRINE CELLS; MACAQUE MONKEY RETINA; INNER PLEXIFORM LAYER; RABBIT RETINA; MAMMALIAN RETINA; SYNAPTIC CONNECTIONS; IMMUNOCYTOCHEMICAL IDENTIFICATION; FUNCTIONAL ARCHITECTURE; ELECTRON-MICROSCOPY; ROD PHOTORECEPTORS AB We surveyed the potential contacts between an identified type of bipolar cell and retinal ganglion cells in the mouse. By crossing two existing mouse strains (line 357 and line GFP-M), we created a double transgenic strain in which GFP is expressed by all members of a single type of ON cone bipolar cell and a sparse, mixed population of retinal ganglion cells. The GFP-expressing bipolar cells appear to be those termed CB4a of Pignatelli W Strettoi [(2004) J. Comp. Neurol., 476, 254-266] and type 7 of Ghosh et al. [(2004) J. Comp. Neurol., 469, 70-82 and J. Comp. Neurol., 476, 202-203]. The labelled ganglion cells include examples of most or all types of ganglion cells present in the mouse. By studying the juxtaposition of their processes in three dimensions, we could learn which ganglion cell types are potential synaptic targets of the line 357 bipolar cell. Of 12 ganglion cell types observed, 10 types could be definitively ruled out as major synaptic targets of the line 357 bipolar cells. One type of monostratified ganglion cell and one bistratified cell tightly cofasciculate with axon terminals of the line 357 bipolar cells. Double labelling for kinesin II demonstrates colocalization of bipolar cell ribbons at the sites of contact between these two types of ganglion cell and the line 357 bipolar cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lin, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. EM blin@helix.mgh.harvard.edu RI Lin, Bin/E-9871-2010 NR 58 TC 26 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2005 VL 21 IS 5 BP 1257 EP 1270 DI 10.1111/j.1460-9568.2005.03967.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 909ZW UT WOS:000227900200012 PM 15813935 ER PT J AU Heine, VM Zareno, J Maslam, S Joels, M Lucassen, PJ AF Heine, VM Zareno, J Maslam, S Joels, M Lucassen, PJ TI Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE corticosteroids; hippocampus; Ki-67; neurogenesis; vasculature ID ENDOTHELIAL GROWTH-FACTOR; NEURAL STEM-CELLS; CHRONIC PSYCHOSOCIAL STRESS; STIMULATES AXONAL OUTGROWTH; NMDA RECEPTOR ACTIVATION; CA3 PYRAMIDAL NEURONS; SMOOTH-MUSCLE-CELLS; HIPPOCAMPAL NEUROGENESIS; NEUROTROPHIC FACTOR; IN-VITRO AB Recent evidence has shown that cell proliferation in the adult hippocampal dentate gyrus occurs in tight clusters located near the vasculature. Also, changes in neurogenesis often appear parallel to changes in angiogenesis. Moreover, both these processes share similar modulating factors, like vascular endothelial growth factor (VEGF) and its receptor Flk-1. In an earlier study we found that chronic stress decreased new cell proliferation in the adult dentate gyrus. We here questioned whether these effects of chronic stress are mediated through the vasculature and whether they involve an angiogenic-signaling pathway. We therefore measured the surface area covered by the vasculature, the proportion of vascular-associated newborn cells, and analysed VEGF and Flk-1 protein expression in the hippocampus of a control, chronically stressed and recovery group of rats. Our results show that 32% of the proliferating cells in the rat hippocampus is vascular associated. Chronic stress affected this population of newborn cells to a significantly larger extent than the non-associated cells. Interestingly, after 3 weeks of recovery, the decreased proliferation not associated with the vasculature was more effectively restored than vascular-associated proportion of proliferating cells. VEGF protein was expressed in high densities in GFAP-positive astrocytes located in the hilus, with VEGF-positive end feet extending into and often contacting the granule cells. After chronic stress, both VEGF and Flk-1 protein levels were significantly decreased in the granular cell layer, and again recovered after 3 weeks. This demonstrates that changes in angiogenic factors are implicated in the decreased adult proliferation found after chronic stress. C1 Univ Amsterdam, Inst Neurobiol, Swammerdam Inst Life Sci, NL-1098 SM Amsterdam, Netherlands. RP Heine, VM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM vivi_heine@dfci.harvard.edu RI Heine, Vivi/F-1741-2011; Joels, Marian/P-6415-2016 NR 108 TC 114 Z9 129 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2005 VL 21 IS 5 BP 1304 EP 1314 DI 10.1111/j.1460-9568.2005.03951.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 909ZW UT WOS:000227900200017 PM 15813940 ER PT J AU Pollack, M Zornberg, G Brock, J Tobias, K Farfel, G AF Pollack, M Zornberg, G Brock, J Tobias, K Farfel, G TI Efficacy of Ppregoahalin in GAD by demographics and baseline severity SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD MAR PY 2005 VL 20 SU 1 BP S178 EP S178 PG 1 WC Psychiatry SC Psychiatry GA 922WE UT WOS:000228869801200 ER PT J AU Albertson, RC Kocher, TD AF Albertson, RC Kocher, TD TI Genetic architecture sets limits on transgressive segregation in hybrid cichlid fishes SO EVOLUTION LA English DT Article DE adaptive radiation; cichlids; jaw; skull; transgressive segregation ID LAKE-MALAWI; PSEUDOTROPHEUS-ZEBRA; ADAPTIVE RADIATION; AFRICAN CICHLIDS; SPECIATION; HYBRIDIZATION; POPULATION; MORPHOLOGY; TELEOSTEI; PERCIFORMES AB The role of hybridization in the evolution of animal species is poorly understood. Transgressive segregation is a mechanism through which hybridization can generate diversity and ultimately lead to speciation. In this report we investigated the capacity of hybridization to generate novel (transgressive) phenotypes in the taxonomically diverse cichlid fishes. We generated a large F(2) hybrid population by crossing two closely related cichlid species from Lake Malawi in Africa with differently shaped heads. Our morphometric analysis focused on two traits with different selective histories. The cichlid lower jaw (mandible) has evolved in response to strong directional selection, and does not segregate beyond the parental phenotype. The cichlid neurocranium (skull) has likely diverged in response to forces other than consistent directional selection (e.g., stabilizing selection), and exhibits marked transgressive segregation in our F2 population. We show that the genetic architecture of the cichlid jaw limits transgression, whereas the genetic basis of skull shape is permissive of transgressive segregation. These data suggest that natural selection, acting through the genome, will limit the degree of diversity that may be achieved via hybridization. Results are discussed in the context of the broader question of how phenotypic diversity may be achieved in rapidly evolving systems. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Univ New Hampshire, Hubbard Ctr Genome Studies, Durham, NH 03824 USA. RP Albertson, RC (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM calbertson@forsyth.org RI Kocher, Thomas/B-3089-2013 NR 38 TC 51 Z9 52 U1 0 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-3820 J9 EVOLUTION JI Evolution PD MAR PY 2005 VL 59 IS 3 BP 686 EP 690 DI 10.1111/j.0014-3820.2005.tb01027.x PG 5 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 910PG UT WOS:000227943400020 PM 15856710 ER PT J AU Oba, Y Lee, JW Ehrlich, LA Chung, HY Jelinek, DF Callander, NS Horuk, R Choi, SJ Roodman, GD AF Oba, Y Lee, JW Ehrlich, LA Chung, HY Jelinek, DF Callander, NS Horuk, R Choi, SJ Roodman, GD TI MIP-1 alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; HUMAN MULTIPLE-MYELOMA; CHEMOKINE RECEPTOR; BONE-DISEASE; PROTEIN 1-ALPHA; NONPEPTIDE CCR1; EXPRESSION; ALPHA; ANTAGONIST; MODULATION AB Objectives. Macrophage inflammatory protein-let (MIP-1 alpha), an osteoclast (OCL) stimulatory factor produced by primary multiple myeloma (MM) cells, increases bone destruction and tumor burden in murine models of MM. Several chemokine receptors (CCR1, CCR5, and CCR9) mediate the effects of MIP-1 alpha. In this study, we determined which of these mediates the effects of MIP-1 alpha on human OCL formation and myeloma cells. Methods. We employed RT-PCR analysis, neutralizing antibodies to CCR1 and CCR5 as well as a CCR1-specific antagonist and OCL formation assays to identify the MIP-1 alpha receptors involved in MIP-1 alpha's effects on myeloma cells and OCL formation. Results. RT-PCR analysis demonstrated that both CCR1 and CCR5 were expressed by highly purified human OCL precursors, myeloma cell lines, and purified marrow plasma cells from MM patients. Neutralizing antibodies to CCR1 or CCR5 inhibited MIP-1 alpha-induced OCL formation. Furthermore, monocyte chemotactic protein-3 (MCP-3), which binds CCR1 but not CCR5 and the CCR1-specific antagonist, BX471, markedly inhibited OCL formation stimulated with MIP-1 alpha. Anti-CCR1, anti-CCR5, or BX471 also inhibited the upregulation of 01 integrin mRNA in myeloma cells induced by MIP-1 alpha, as well as the adherence of myeloma cells to stromal cells and IL-6 production by stromal cells in response to myeloma cells. Conclusion. These data demonstrate that MIP-1 alpha utilizes either CCR1 or CCR5 for its effects on OCL formation and myeloma cells, and that blocking either CCR1 or CCR5 inhibits OCL formation and myeloma cell adhesion to stromal cells. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Univ Pittsburgh, Inst Canc, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. Dept Vet Affairs, Ctr Med, Pittsburgh, PA USA. Mayo Clin, Dept Immunol, Rochester, MN USA. Univ Texas, Ctr Hlth Sci, Dept Med Hematol, San Antonio, TX 78285 USA. Berlex Biosci, Richmond, CA USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, Res & Dev, 151-U,Univ Dr, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 26 TC 97 Z9 104 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2005 VL 33 IS 3 BP 272 EP 278 DI 10.1016/j.exphem.2004.11.015 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 908ZS UT WOS:000227829300002 PM 15730850 ER PT J AU Haining, WN Cardoso, AA Keczkemethy, HL Fleming, M Neuberg, D DeAngelo, DJ Stone, RM Galinsky, I Silverman, LB Sallan, SE Nadler, LM Guinan, EC AF Haining, WN Cardoso, AA Keczkemethy, HL Fleming, M Neuberg, D DeAngelo, DJ Stone, RM Galinsky, I Silverman, LB Sallan, SE Nadler, LM Guinan, EC TI Failure to define window of time for autologous tumor vaccination in patients with newly diagnosed or relapsed acute lymphoblastic leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA CELLS; NON-HODGKIN-LYMPHOMA; CD40 LIGAND; T-CELLS; INTENSIVE CHEMOTHERAPY; ANTITUMOR IMMUNITY; ADOPTIVE TRANSFER; DENDRITIC CELLS; GENE-TRANSFER AB Objectives. We and others have shown that B cell precursor acute lymphoblastic leukemia cells (ALL) stimulated with CD40 ligand become efficient antigen-presenting cells (APC) capable of expanding autologous, tumor-specific T cells from patients. Translation of these preclinical findings to a novel treatment strategy required four separate issues to be determined: (1) if a CD40-ALL vaccine could be generated for clinical use; (2) whether clinical translation could be achieved; (3) whether the vaccination was safe; and (4) whether a window of time could be identified that would optimize the efficacy of vaccination. Patients and Methods. Nine patients with relapsed/refractory ALL were enrolled in a phase I trial of vaccination with autologous CD40-ALL. Immunologic reconstitution was measured in a separate cohort of 23 patients with newly diagnosed ALL. Results. We successfully prepared autologous vaccines for all nine patients in the phase I trial. CD40-ALL were potent APC, capable of stimulating allogeneic and peptide-specific T cells in vitro. Two patients were vaccinated without adverse events. Five patients died or progressed before vaccination, suggesting that rapid disease progression limits vaccination in patients with relapse disease, thus limiting clinical translation. We therefore sought to identify a window of time for vaccination during which this approach might be feasible. To achieve this end, we evaluated immunological reconstitution in newly diagnosed patients with ALL patients. Despite recovery of myelopoiesis, most patients had profound defects in T, B, and natural killer (NK) cell numbers that failed to recover at any point during therapy. Conclusion. Autologous tumor vaccination at a time of ALL relapse is not feasible. Alternative strategies for immunotherapy of ALL may require ex vivo generation of antigen specific T cells and adoptive therapy. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU NCI NIH HHS [P01CA68484]; NHLBI NIH HHS [K08HL72750] NR 49 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2005 VL 33 IS 3 BP 286 EP 294 DI 10.1016/j.exphem.2004.12.001 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 908ZS UT WOS:000227829300004 PM 15730852 ER PT J AU Giovino, MA Wang, H Sykes, M Yang, YG AF Giovino, MA Wang, H Sykes, M Yang, YG TI Role of VLA-4 and VLA-5 in ex vivo maintenance of human and pig hematopoiesis in human stroma-supported long-term cultures SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID CELL-ADHESIVE FUNCTION; BONE-MARROW; TOLERANCE INDUCTION; STEM-CELLS; HUMAN FIBRONECTIN; MIXED CHIMERISM; C-KIT; PREPARATIVE REGIMEN; ALLOGRAFT TOLERANCE; XENOGENEIC BARRIER AB Objective. The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta 1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environment. Methods. Porcine and human c-kit(+) bone marrow cells were purified and cultured on human bone marrow stroma for 6 weeks. The role of VLA-4 and VLA-5 in the maintenance of porcine vs human hematopoiesis in this human stroma-supported long-term bone marrow culture (LTBMC) system was evaluated by using blocking mAbs that bind to both species. Results. Blocking VLA-4 with HP2/1 inhibited both human and porcine hematopoiesis, whereas anti-VLA-5 (SAM-1) suppressed the function of human, but not porcine, hematopoietic cells. In mixed LTBMC of porcine and human cells on a human stroma, porcine hematopoietic cells were at a competitive disadvantage, as seen by a rapid decline in cellularity, including clonogenic progenitors. This disadvantage was substantially overcome by the addition of SAM-1. Furthermore, human, but not porcine, cell adhesion to human fibronectin was inhibited by arginine-glycine-aspartic acid (RGD) peptides. Conclusion. Taken together, these results indicate that VLA-4 plays critical role for porcine hematopoiesis in a human hematopoietic environment, and raise the possibility that porcine VLA-5 might be unable to bind the respective human ligand and/or to initiate adequate post-ligand-binding signaling. Thus, VLA-5 may provide a potential target for developing approaches to improve porcine hematopoiesis in human recipients. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. Immerge BioTherapeut Inc, Cambridge, MA USA. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Surg Serv, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL54038] NR 43 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2005 VL 33 IS 3 BP 363 EP 370 DI 10.1016/j.exphem.2004.11.011 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 908ZS UT WOS:000227829300012 PM 15730860 ER PT J AU Lee, PW Cina, RA Randolph, MA Goodrich, J Rowland, H Arellano, R Kim, HB Sachs, DH Huang, CA AF Lee, PW Cina, RA Randolph, MA Goodrich, J Rowland, H Arellano, R Kim, HB Sachs, DH Huang, CA TI Stable multilineage chimerism across full MHC barriers without graft-versus-host disease following in utero bone marrow transplantation in pigs SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; MONOCLONAL-ANTIBODIES; T-CELLS; MINIATURE SWINE; INUTERO TRANSPLANTATION; MICE; ENGRAFTMENT; INDUCTION; TOLERANCE AB Stable engraftment of hematopoietic progenitors and multilineage chimerism following in utero bone marrow transplantation could be a promising modality for treatment of prenatally diagnosed blood dyscrasias. For treatment of these diseases, stable chimerism in the myeloid and erythroid lineages is important because it is anticipated that donor-derived cells will compensate for defects in these host lineages. In the present study, a preparation of bone marrow that includes fresh, unmanipulated marrow mixed with T-cell-depleted marrow to achieve 1.5% T-cell content, was injected into the intrahepatic portion of the umbilical vein of porcine fetuses at mid-gestation. Donor hematopoietic progenitor cell engraftment was assessed in fetal liver and recipient bone marrow postnatally by donor-specific polymerase chain reaction of colony-forming units. Chimerism was assessed in lymphoid tissues and peripheral blood by flow cytometry. Graft-versus-host disease (GVHD) was assessed by histological analysis of biopsies of skin, bone marrow, liver, and intestine. In this report, we demonstrate that stable multilineage chimerism across a full major histocompatibility complex disparity can be achieved without GVHD through in utero bone marrow transplantation. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Huang, CA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149-9019,13th St, Boston, MA 02129 USA. EM huangc@helix.mgh.harvard.edu NR 31 TC 16 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2005 VL 33 IS 3 BP 371 EP 379 DI 10.1016/j.exphem.2004.12.002 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 908ZS UT WOS:000227829300013 PM 15730861 ER PT J AU Mayerhofer, M Aichberger, KJ Florian, S Krauth, MT Hauswirth, AW Derdak, S Sperr, WR Esterbauer, H Wagner, O Marosi, C Pickl, WF Deininger, M Weisberg, E Druker, BJ Griffin, JD Sillaber, C Valent, P AF Mayerhofer, M Aichberger, KJ Florian, S Krauth, MT Hauswirth, AW Derdak, S Sperr, WR Esterbauer, H Wagner, O Marosi, C Pickl, WF Deininger, M Weisberg, E Druker, BJ Griffin, JD Sillaber, C Valent, P TI Identification of mTOR as a novel bifunctional target in chronic myeloid leukemia: dissection of growth-inhibitory and VEGF-suppressive effects of rapamycin in leukemic cells SO FASEB JOURNAL LA English DT Article DE CML; Bcr-Abl; imatinib; vascular endothelial growth factor ID CHRONIC MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; INDUCED G(1) ARREST; BCR-ABL; IMATINIB MESYLATE; CYTOGENETIC RESPONSES; MAMMALIAN PROTEIN; RESIDUAL DISEASE; INTERFERON-ALPHA; CANCER-THERAPY AB The mammalian target of rapamycin (mTOR) has recently been described to be constitutively activated in B cr-Abl-transformed cells and to mediate rapamycin-induced inhibition of growth in respective cell lines. We have recently shown that rapamycin down-regulates expression of vascular endothelial growth factor (VEGF), a mediator of leukemia-associated angiogenesis, in primary CML cells. In the present study, we analyzed growth-inhibitory in vitro and in vivo effects of rapamycin on primary CML cells and asked whether rapamycin-induced suppression of VEGF in leukemic cells is related to growth inhibition. Rapamycin dose dependently inhibited growth of primary CML cells obtained from patients with imatinib-responsive or imatinib-resistant disease as well as growth of B cr-Abl-transformed imatinib-resistant cell lines. Moreover, we observed potent cytoreductive effects of rapamycin in a patient with imatinib-resistant Bcr-Abl+ leukemia. The growth-inhibitory effects of rapamycin on CML cells were found to be associated with G1 cell cycle arrest and with induction of apoptosis. In all cell types tested, rapamycin was found to down-regulate expression of VEGF. However, exogenously added VEGF did not counteract the rapamycin-induced decrease in proliferation. In conclusion, rapamycin inhibits growth of CML cells in vitro and in vivo and, in addition, down-regulates expression of VEGF. Both effects may contribute to the antileukernic activity of the drug in CML. C1 Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, A-1097 Vienna, Austria. Med Univ Vienna, Inst Immunol, A-1097 Vienna, Austria. Med Univ Vienna, Clin Inst Med & Chem Lab Diagnost, A-1097 Vienna, Austria. Med Univ Vienna, Dept Internal Med 1, Div Oncol, A-1097 Vienna, Austria. Oregon Hlth Sci Univ, Inst Canc, Ctr hematol Malignancies, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Portland, OR USA. RP Mayerhofer, M (reprint author), Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Waehringer Guertel 18-20, A-1097 Vienna, Austria. EM matthias.mayerhofer@univie.ac.at RI Pickl, Winfried/E-5682-2011 NR 63 TC 51 Z9 53 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2005 VL 19 IS 3 BP 960 EP + DI 10.1096/fj.04-1973fje PG 27 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 910AH UT WOS:000227901300007 PM 15784722 ER PT J AU Kim, A Murphy, MP Oberley, TD AF Kim, A Murphy, MP Oberley, TD TI Mitochondrial redox state regulates transcription of the nuclear-encoded mitochondrial protein manganese superoxide dismutase: a proposed adaptive response to mitochondrial redox imbalance SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE MnSOD; thioredoxin 2; transcription; mRNA; mitochondrial redox; H2O2; mitochondrial antioxidant; MitoQ; free radicals ID PROSTATE CARCINOMA-CELLS; CYSTEINE SULFINIC ACID; REACTIVE OXYGEN; NIH/3T3 FIBROBLASTS; OXIDATIVE STRESS; OVEREXPRESSION; INHIBITION; PEROXIREDOXINS; ANTIOXIDANT; MODULATION AB Overexpression of human manganese superoxide dismutase (MnSOD) in mouse NIH/3T3 cells using an inducible retroviral system led to alterations in the mitochondrial redox state since levels of reactive oxygen species rapidly increased after induction of human MnSOD (Antioxid. Redox Signal. 6:489-500; 2004). Alterations in exogenous human MnSOD led to large increases in levels of endogenous mouse MnSOD (sod2) and thioredoxin 2 (txn2) mRNAs, but smaller increases in MnSOD and thioredoxin 2 protein expression. Tight regulation of mitochondrial protein levels seems to be necessary for optimal cellular function, since mitochondrial antioxidant protein levels did not increase to the same extent as antioxidant protein mRNA levels. We hypothesize that these changes in antioxidant proteins are adaptations to the altered mitochondrial redox state elicited by MnSOD overexpression. The mitochondrial-specific antioxidant MitoQ reversed cell growth inhibition, and greatly decreased levels of endogenous sod2 and txn2 transcripts following induction of exogenous MnSOD. Elevated levels of mouse sod2 transcripts resulted from transcriptional activation of the endogenous sod2 gene since actinomycin D prevented transcription of this gene. Therefore, the mitochondrial redox state appears to modulate a nuclear-driven biochemical event, i.e., transcriptional activation of a nuclear gene encoding a protein targeted to mitochondria. (C) 2004 Elsevier Inc. All rights reserved. C1 William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI USA. MRC, Dunn Human Nutr Unit, Cambridge, England. Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu RI Murphy, Michael/C-2120-2009 OI Murphy, Michael/0000-0003-1115-9618 NR 31 TC 30 Z9 30 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 1 PY 2005 VL 38 IS 5 BP 644 EP 654 DI 10.1016/j.freeradbiomed.2004.10.030 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 898CY UT WOS:000227054900011 PM 15683720 ER PT J AU Shaib, YH El-Serag, HB Davila, JA Morgan, R McGlynn, KA AF Shaib, YH El-Serag, HB Davila, JA Morgan, R McGlynn, KA TI Risk factors of intrahepatic cholangiocarcinoma in the United States: A case-control study SO GASTROENTEROLOGY LA English DT Article ID HEPATITIS-C VIRUS; PRIMARY SCLEROSING CHOLANGITIS; DIABETES-MELLITUS; LIVER-CANCER; POPULATION; INFECTION; CARCINOMA; CIRRHOSIS; DENMARK; COHORT AB Background & Aims: The incidence of intrahepatic cholangiocarcinoma has been recently increasing in the United States. In this case-control study, we used the Surveillance, Epidemiology, and End Results-Medicare database to evaluate the prevalence of known risk factors for intrahepatic cholangiocarcinoma and explore other potential risk factors. Methods: We identified all patients with intrahepatic cholangiocarcinoma aged 65 years and older diagnosed between 1993 and 1999 in the population-based Surveillance, Epidemiology, and End Results registries (14% of the US population). Controls were randomly chosen from individuals without any cancer diagnosis in the underlying population of the Surveillance, Epidemiology, and End Results regions. We obtained information on risk factors from Medicare claims (parts A and 13) for all cases and controls with at least 2 years of continuous Medicare enrollment. Unadjusted and adjusted odds ratios were calculated in logistic regression analysis. Results: A total of 625 cases and 90,834 controls satisfied the inclusion and exclusion criteria. Cases were older than controls (78.7 vs. 76.5 years; P = .02) and were more likely to be male (48.3% vs. 36.8%; P < .0001). The racial composition was similar between cases and controls. Several risk factors were significantly more prevalent among cases. These included nonspecific cirrhosis (adjusted odds ratio, 27.2; P < .0001), alcoholic liver disease (adjusted odds ratio, 7.4; P < .0001), hepatitis C virus infection (adjusted odds ratio, 6.1; P < .0001), human immunodeficiency virus infection (adjusted odds ratio, 5.9; P = .003), diabetes (adjusted odds ratio, 2.0; P < .0001), and inflammatory bowel diseases (adjusted odds ratio, 2.3; P = .002). Conclusions: This population-based study shows that in addition to previously well described risk factors, several others could be associated with intrahepatic cholangiocarcinoma. These include hepatitis C virus, human immunodeficiency virus, liver cirrhosis, and diabetes. C1 Baylor Coll Med, Michael E Debakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Michael E Debakey Vet Affairs Med Ctr, Dept Gastroenterol, Houston, TX 77030 USA. NCI, NIH, Dept Human & Hlth Serv, Bethesda, MD 20892 USA. RP Shaib, YH (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM yshalb@bcm.tmc.edu NR 18 TC 248 Z9 262 U1 1 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2005 VL 128 IS 3 BP 620 EP 626 DI 10.1053/j.gastro.2004.12.048 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 903SO UT WOS:000227446100015 PM 15765398 ER PT J AU Ioannou, GN Weiss, NS Boyko, EJ Kahn, SE Lee, SP AF Ioannou, GN Weiss, NS Boyko, EJ Kahn, SE Lee, SP TI Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease SO GASTROENTEROLOGY LA English DT Article ID NONALCOHOLIC FATTY LIVER; CHRONIC HEPATITIS-C; INSULIN-RESISTANCE; UNITED-STATES; NATURAL-HISTORY; VIRUS-INFECTION; US ADULTS; STEATOHEPATITIS; OBESITY; ASSOCIATION AB Background & Aims: Nonalcoholic fatty liver disease has been defined by the presence of hepatic steatosis in the absence of other chronic liver diseases. We sought to determine whether obesity, insulin resistance, and the metabolic syndrome, which are the main risk factors for nonalcoholic fatty liver disease, are associated with similar elevations in serum alanine aminotransferase activity in persons with and those without other causes of chronic liver disease. Methods: Adult participants of the third National Health and Nutrition Examination Survey were divided into those with causes of chronic liver disease (n = .1037), defined as viral hepatitis, excessive alcohol consumption, or increased transferrin-iron saturation, and those without (n = 8004). Result : Among persons with other causes of chronic liver disease, obesity (adjusted odds ratio, 4.9; 95% confidence interval, 2.5-9.4), insulin resistance (adjusted odds ratio, 6.8; 95% confidence interval, 3.0-15.5, comparing the highest and the lowest quartile), and the metabolic syndrome (adjusted odds ratio, 3.3; 95% confidence interval, 1.4-8.0) were all strongly associated with increased alanine aminotransferase activity (> 43 IU/L). Among persons without other causes of chronic liver disease, statistically similar associations were identified. Conclusions: Obesity, insulin resistance, and the metabolic syndrome are strong predictors of increased alanine aminotransferase activity in the US population, both in persons with and in persons without other causes of chronic liver disease. We hypothesize that metabolic fatty liver disease related to these conditions is the cause of the increased alanine aminotransferase activity and may be under-recognized in persons with other causes of chronic liver disease. C1 Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Endocrinol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Nutr, Seattle, WA USA. Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Seattle Vet Affairs Med Ctr, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu RI Lee, Sum Ping/C-4333-2009; OI Kahn, Steven/0000-0001-7307-9002 NR 52 TC 49 Z9 50 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2005 VL 128 IS 3 BP 627 EP 635 DI 10.1043/j.gastro.2004.12.004 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 903SO UT WOS:000227446100016 PM 15810122 ER PT J AU El-Serag, HB AF El-Serag, HB TI Obesity and disease of the esophagus and colon SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID BODY-MASS INDEX; GASTROESOPHAGEAL-REFLUX DISEASE; Y GASTRIC BYPASS; RISK-FACTORS; ADENOMATOUS POLYPS; SPHINCTER PRESSURE; COLORECTAL-CANCER; HIATAL-HERNIA; UNITED-STATES; FAT INTAKE AB This article discusses the evidence linking obesity to the different manifestations of gastroesophageal reflux disease and colorectal cancer. C1 Baylor Coll Med, Gastroenterol Sect, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Baylor Coll Med, Gastroenterol Sect, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 62 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2005 VL 34 IS 1 BP 63 EP + DI 10.1016/j.gtc.2004.12.006 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 921KA UT WOS:000228761900007 PM 15823439 ER PT J AU Kaplan, LM AF Kaplan, LM TI Pharmacological therapies for obesity SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; VALVULAR HEART-DISEASE; TERM WEIGHT CONTROL; DOUBLE-BLIND; SIBUTRAMINE; ORLISTAT; PHARMACOTHERAPY; PLACEBO; METAANALYSIS; REDUCTION AB Pharmacological therapy for obesity is in transition. Historically, there have been few effective agents, and many have been withdrawn because of unacceptable side effects. Current options include three medications approved by the FDA for the treatment of obesity: phentermine, sibutramine and orlistat. Phentermine and sibutramine suppress appetite and promote thermogenesis, and orlistat blocks fat digestion and absorption in the gut. Several drugs approved for other indications often promote weight loss, including bupropion, metformin, topiramate and zonisamide; they have been used empirically for treatment of obesity and to counter the weight-promoting effects of other medications. Expanding knowledge of the physiological mechanisms of body weight regulation has revealed new molecular targets, and more than 150 novel agents are under active development. Because weight regulation is complex, and redundant systems protect against perceived starvation, optimal treatment of obesity will likely require combinations of therapies. The accelerating emergence of new medications will facilitate the development of such effective combinations. C1 Massachusetts Gen Hosp, Weight Ctr, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Weight Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Weight Ctr, Dept Med, 50 Staniford St, Boston, MA 02114 USA. EM lmkaplan@partners.org FU NIDDK NIH HHS [DK99010, DK46200, DK43351] NR 31 TC 37 Z9 40 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2005 VL 34 IS 1 BP 91 EP + DI 10.1016/j.gtc.2004.12.002 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 921KA UT WOS:000228761900009 PM 15823441 ER PT J AU Kaplan, LM AF Kaplan, LM TI Gastrointestinal management of the bariatric surgery patient SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID GASTRIC BYPASS-SURGERY; MORBID-OBESITY; BILIOPANCREATIC DIVERSION; WERNICKES ENCEPHALOPATHY; COMPLICATIONS; THERAPY; ONSET AB The use of gastrointestinal (GI) weight loss surgery to treat severe and medically complicated obesity has increased rapidly in recent years. Although highly effective, these surgical procedures often are associated with complications that can adversely affect the health and quality of life of its recipients. Beyond the acute peri-operative period, GI and nutritional complications are most common. As a result, gastroenterologists can make an important contribution to the preoperative evaluation and postoperative care of these patients. The preoperative GI evaluation should exclude distal gastric disease, occult GI bleeding, and esophageal dysmotility; identify hepatobiliary disease; and identify and correct nutritional deficiencies. Optimal postoperative care includes efforts to prevent GI and nutritional complications, efficient evaluation and treatment for GI symptoms, and monitoring and treating micronutrient deficiencies. Active participation of the gastroenterologist in the multi-disciplinary team that cares for patients undergoing weight loss surgery can help optimize the outcomes and reduce the risks associated with these important but complex therapies. C1 Massachusetts Gen Hosp, Weight Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Weight Ctr, Gastrointestinal Unit, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM lmkaplan@partners.org FU NIDDK NIH HHS [DK43351, DK46200, DK99010] NR 20 TC 24 Z9 26 U1 0 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2005 VL 34 IS 1 BP 105 EP + DI 10.1016/j.gtc.2004.12.004 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 921KA UT WOS:000228761900010 PM 15823442 ER PT J AU Lieberman, D AF Lieberman, D TI Quality and colonoscopy: a new imperative SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID PREVENT COLORECTAL ADENOMAS; CLINICAL IMPORTANCE; RANDOMIZED-TRIAL; FLAT ADENOMAS; CANCER; RECURRENCE; SIGMOIDOSCOPY; TUMORIGENESIS; ASPIRIN; CALCIUM C1 Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97201 USA. RP Lieberman, D (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97201 USA. NR 28 TC 24 Z9 24 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2005 VL 61 IS 3 BP 392 EP 394 DI 10.1016/S0016-5107(05)00133-1 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 909LL UT WOS:000227861300007 PM 15758909 ER PT J AU Gaynes, BN Rush, AJ Trivedi, M Wisniewski, SR Balasubramani, GK Spencer, DC Petersen, T Klinkman, M Warden, D Schneider, RK Castro, DB Golden, RN AF Gaynes, BN Rush, AJ Trivedi, M Wisniewski, SR Balasubramani, GK Spencer, DC Petersen, T Klinkman, M Warden, D Schneider, RK Castro, DB Golden, RN TI A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE primary care; depression; suicidality; clinical trial ID SEQUENCED TREATMENT ALTERNATIVES; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ILLNESS RATING-SCALE; QUALITY-OF-LIFE; PSYCHIATRIC-PATIENTS; MAJOR DEPRESSION; GENERAL-PRACTICE; ANTIDEPRESSANT TREATMENT; MINOR DEPRESSION AB Purpose: No study has directly compared the clinical features of depression for patients entering clinical trials using identical enrollment criteria at primary care (PC) and specialty care (SC) settings. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (http://www.star-d.org) provides a unique opportunity to provide this comparison for patients with a major depressive disorder (MDD) requiring treatment. Subjects and Methods: We report baseline data for the first 1500 patients enrolled in this trial involving 41 clinic sites (18 PC, 23 SC). Broadly inclusive eligibility criteria required that patients have a DSM-IV diagnosis of nonpsychotic MDD, have not failed an adequate medication trial during their current episode and score >= 14 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) Primary outcomes included the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C-30) and the HAM-D17. Results: Specialty care and PC patients had equivalent degrees of depressive severity (IDS-C-30=35.8; HAM-D-17=20.4). Specialty care patients were almost twice as likely to report a prior suicide attempt than PC patients (21% vs. 12%, P <.0001) and slightly less likely to endorse suicidal ideation in the past week (45.0% vs. 50.8%, P=.006). The only other distinguishing core symptoms were a slightly lower likelihood of PC patients endorsing depressed mood (95.2% vs. 97.7%, P=.032) or anhedonia (66.3% vs. 70.7%, P=.042, IDS-C30) and a lower likelihood of PC patients endorsing weight loss (IDS-C30). HAM-D-17 results were identical. Conclusion: Depressive severity was not different, and symptomatic presentations did not differ substantially. Major depressive disorder is more similar than different among patients at SC and PC settings. Thus, similar clinical and research methods for screening, detecting and measuring treatment outcomes can be applied in both settings. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Psychiat, Richmond, VA 23220 USA. Univ Calif Los Angeles, Sch Med, Dept Family Med, Harbor City, CA 90710 USA. RP Gaynes, BN (reprint author), Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. EM bngaynes@med.unc.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [K23 MH01951-03, N01MH90003] NR 52 TC 48 Z9 48 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAR-APR PY 2005 VL 27 IS 2 BP 87 EP 96 DI 10.1016/j.genhosppsych.2004.10.003 PG 10 WC Psychiatry SC Psychiatry GA 911VS UT WOS:000228035000001 PM 15763119 ER PT J AU Beppu, H Lei, H Bloch, KD Li, E AF Beppu, H Lei, H Bloch, KD Li, E TI Generation of a floxed allele of the mouse BMP type II receptor gene SO GENESIS LA English DT Article DE BMP; receptor; gene targeting; Cre-loxP ID PRIMARY PULMONARY-HYPERTENSION; BETA FAMILY; PATHWAYS; CANCER AB Bone morphogenetic proteins (BMPs) regulate a wide range of cellular functions that contribute to embryonic development from mesoderm formation to organogenesis. BMP type II receptor (BMPR-II) transduces BMP signals by forming heteromeric complexes with and phosphorylating BMP type I receptors. Heterozygous germline mutations of BMPR-H gene have been identified in patients with familial and sporadic primary pulmonary hypertension, indicating that BMPR-II may contribute to the maintenance of normal pulmonary vascular structure and function. Since embryos homozygous for a null BMPR-U allele died during gastrulation, precluding further studies of BMPR-II function in organ formation and in adult tissues, we generated mice carrying a conditional mutant BMPR-H allele in which exons 4 and 5 were flanked by loxP sequences. We anticipate that studies of mice carrying a floxed BMPR-H allele and a Cre transgene (under the control of a tissue-specific promoter) will enable characterization of the role of BMPR-II in specific cell types during development and in the pathogenesis of cardiovascular diseases. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Li, E (reprint author), Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA. EM en.li@pharma.novartis.com FU NHLBI NIH HHS [HL-74352]; NICHD NIH HHS [HD-35286] NR 18 TC 27 Z9 27 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD MAR PY 2005 VL 41 IS 3 BP 133 EP 137 DI 10.1002/gene.20099 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 913TR UT WOS:000228176700005 PM 15736264 ER PT J AU Henkes, LE Silva, WA Moraes, JCF Weimer, TA AF Henkes, LE Silva, WA Moraes, JCF Weimer, TA TI Mitochondrial control region genetic diversity and maternal ancestry of a Brangus-Ibage cattle populations SO GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE bovine mtDNA; maternal lineage; sequence analysis; beef cattle; genetic diversity ID DAIRY-CATTLE; DNA; SEQUENCE; GENOME; MTDNA; SUBSTITUTIONS; BOOTSTRAP; NUMBER AB The genetic diversity of 277 nucleotides in the mitochondrial DNA control region (nt 15,964 to 16,240 in reference sequence) was analyzed in crossbreed beef cattle (Brangus-lbage, 5/8 Bos primigenius taurus x 3/8 Bosprimigenius indicus) as well as in some Nellore samples (B. p. indicus). Fifty-seven mutations were found in Brangus-lbage comprising 18 haplotypes (haplotype diversity, h = 0.851 +/- 0.041 and nucleotide diversity, ntd = 0.009 +/- 0.006) and 66 in Nellore (h = 1.00 +/- 0.27, ntd = 0.014 +/- 0.012). These data indicated sequence identities of 99.6 and 92.1 % between the B. p. taurus reference sequence and Brangus-lbage and Nellore, respectively. The comparison of our data with sequence data for 612 individuals recovered from GenBank showed a total of 205 haplotypes defined by 99 polymorphic sites. Most of the variability (53 %) was due to differentiation within breeds. The phylogenetic tree constructed using the neighbor-joining method showed clearly the well-known dichotomy between B. p. taurus and B. p. indicus. The Brangus-lbage clustered with B. p. taurus lineages; however, the displacement of Nellore from B. p. indicus branch probably indicates a substantial B. p. taurus maternal ancestry in some Nellore samples (obtained from GenBank) and reflects the primarily male-driven introduction of this breed in Brazil. C1 Univ Fed Rio Grande Sul, Dept Genet, Porto Alegre, RS, Brazil. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02115 USA. Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil. Empresa Brasileira Pesquisa Agropecuaria, Baga, RS, Brazil. Univ Luterana Brasil, Hosp Vet, Lab Biotecnol Anim, Conoas, RS, Brazil. RP Weimer, TA (reprint author), Duque Caxias 910-101, BR-90010280 Porto Alegre, RS, Brazil. EM taw@plug-in.com.br RI Moraes, Jose Carlos/D-6593-2013; Silva Jr, Wilson Araujo/E-9487-2011 OI Silva Jr, Wilson Araujo/0000-0001-9364-2886 NR 33 TC 1 Z9 2 U1 0 U2 3 PU SOC BRASIL GENETICA PI RIBEIRAO PRET PA RUA CAP ADELMIO NORBET DA SILVA, 736, ALTO DA BOA VISTA, 14025-670 RIBEIRAO PRET, BRAZIL SN 1415-4757 J9 GENET MOL BIOL JI Genet. Mol. Biol. PD MAR PY 2005 VL 28 IS 1 BP 60 EP 66 DI 10.1590/S1415-47572005000100011 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 951KM UT WOS:000230929100011 ER PT J AU Formstecher, E Aresta, S Collura, V Hamburger, A Meil, A Trehin, A Reverdy, C Betin, V Maire, S Brun, C Jacq, B Arpin, M Bellaiche, Y Bellusci, S Benaroch, P Bornens, M Chanet, R Chavrier, P Delattre, O Doye, V Fehon, R Faye, G Galli, T Girault, JA Goud, B de Gunzburg, J Johannes, L Junier, MP Mirouse, V Mukherjee, A Papadopoulo, D Perez, F Plessis, A Rosse, C Saule, S Stoppa-Lyonnet, D Vincent, A White, M Legrain, P Wojcik, J Camonis, J Daviet, L AF Formstecher, E Aresta, S Collura, V Hamburger, A Meil, A Trehin, A Reverdy, C Betin, V Maire, S Brun, C Jacq, B Arpin, M Bellaiche, Y Bellusci, S Benaroch, P Bornens, M Chanet, R Chavrier, P Delattre, O Doye, V Fehon, R Faye, G Galli, T Girault, JA Goud, B de Gunzburg, J Johannes, L Junier, MP Mirouse, V Mukherjee, A Papadopoulo, D Perez, F Plessis, A Rosse, C Saule, S Stoppa-Lyonnet, D Vincent, A White, M Legrain, P Wojcik, J Camonis, J Daviet, L TI Protein interaction mapping: A Drosophila case study SO GENOME RESEARCH LA English DT Article ID INTERACTION MAP; SACCHAROMYCES-CEREVISIAE; HELICOBACTER-PYLORI; 2-HYBRID ANALYSIS; TUMOR-SUPPRESSOR; YEAST PROTEOME; C-ELEGANS; RAS; MELANOGASTER; COMPLEXES AB The Drosophila (fruit fly) model system has been instrumental ill our current Understanding of human biology, development, and diseases. Here, we Used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional Motifs allow the elaboration of known complexes and the identification of new ones. The full data set call be visualized Using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps. C1 Inst Curie, Hybrigen Lab, F-75248 Paris, France. Hybrigen, F-75014 Paris, France. CNRS, UMR 144, F-75014 Paris, France. INSERM, U520, F-75014 Paris, France. INSERM, U509, F-75014 Paris, France. INSERM, U528, F-75014 Paris, France. CNRS, UMR 218, F-75014 Paris, France. Inst Curie, Serv Genet, Med Sect, F-75014 Paris, France. LGPD, IBDM, F-13288 Marseille, France. Inst Curie, CNRS, UMR 146, F-91405 Orsay, France. Duke Univ, Dept Biol, Durham, NC 27708 USA. Inst Fer Moulin, INSERM, U536, F-75005 Paris, France. Coll France, INSERM, U114, F-75231 Paris, France. INSERM, UMR 384, F-63001 Clermont Ferrand, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Inst Jacques Monod, CNRS, UMR 7592, F-75251 Paris, France. Univ Toulouse 3, CNRS, UMR 5547, F-31062 Toulouse, France. UT Sw Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. RP Camonis, J (reprint author), Inst Curie, Hybrigen Lab, F-75248 Paris, France. EM jcamonis@curie.fr; ldaviet@hybrigenics.fr RI Girault, Jean-Antoine/F-7518-2013; Marion-Poll, Frederic/D-8882-2011; CHAVRIER, Philippe/B-4707-2010; Brun, Christine/B-4922-2008; Galli, Thierry/G-8842-2011; OI Girault, Jean-Antoine/0000-0002-7900-1705; Marion-Poll, Frederic/0000-0001-6824-0180; CHAVRIER, Philippe/0000-0002-7351-733X; Brun, Christine/0000-0002-5563-6765; Galli, Thierry/0000-0001-8514-7455; Perez, Franck/0000-0002-9129-9401 NR 39 TC 302 Z9 321 U1 2 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAR PY 2005 VL 15 IS 3 BP 376 EP 384 DI 10.1101/gr.2659105 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 902CB UT WOS:000227327800005 PM 15710747 ER PT J AU Nanthakumar, NN Dai, DW Meng, D Chaudry, N Newburg, DS Walker, WA AF Nanthakumar, NN Dai, DW Meng, D Chaudry, N Newburg, DS Walker, WA TI Regulation of intestinal ontogeny: effect of glucocorticoids and luminal microbes on galactosyltransferase and trehalase induction in mice SO GLYCOBIOLOGY LA English DT Article DE germ-free mice; hormonal regulation; microflora; postnatal development ID RAT SMALL-INTESTINE; BETA-1,4-GALACTOSYLTRANSFERASE KNOCKOUT MICE; EPITHELIAL-CELLS; NECROTIZING ENTEROCOLITIS; TERMINAL GLYCOSYLATION; DEVELOPMENTAL-CHANGES; POSTNATAL-DEVELOPMENT; INDUCED MATURATION; ECOSYSTEM; EXPRESSION AB Intestinal maturation can be influenced by intrinsic factors (glucocorticoid hormones) and by extrinsic factors (resident microflora); their relative roles in ontogeny of mouse intestinal trehalase expression, a marker of general gut development, and of beta1,4-galactosyltransferase (betaGT), a marker of glycosyltransferase development, were investigated. In conventional (CONV) mice, betaGT and trehalase gene expression rapidly increased to adult levels by the fourth postnatal week.,In germ-free (GF) mice, betaGT expression remained at initial low levels and was rapidly induced on reintroduction of luminal microbes of the adult gut but not of microbes characteristic of the suckling gut. Similar developmental patterns were observed for colonic galactosyl beta1,4-linked glycoconjugates, products of betaGT. activity. These results indicate an essential role for microbes in the ontogeny of betaGT. In both CONV and GF mice, cartisone acetate (CA) precociously accelerated the ontogeny of betaGT and trehalase until maturation of the gut occurred (day 22). In the mature gut of CONV mice, both betaGT and trehalase are elevated and insensitive to CA; in GF mature mice, the expression of betaGT remains low, whereas the expression of trehalase was at mature levels, regardless of CA treatment. These changes in enzyme activity were accompanied by parallel changes in mRNA, implying transcriptional regulation. Thus both microbes and cortisone regulate gut ontogeny, but only suckling gut responds to CA, an intrinsic factor, whereas adult gut betaGT expression remains sensitive to microflora, an extrinsic factor. However, induction of the adult pattern of glycosyltransferase expression in mature gut requires colonization by microflora typical of adult gut, suggesting an essential role for intestinal colonization in the ontogeny of normal intestinal mucosal cell surface glycoconjugate receptors. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nanthakumar, NN (reprint author), Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, 114 16th St, Charlestown, MA 02129 USA. EM nanthaku@helix.mgh.harvard.edu FU FIC NIH HHS [D43 TW1265]; NICHD NIH HHS [HD12437, HD13021, HD31852]; NIDDK NIH HHS [P01-DK33506, DK 59811, P30-DK40561] NR 51 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD MAR PY 2005 VL 15 IS 3 BP 221 EP 232 DI 10.1093/glycob/cwi004 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 896IA UT WOS:000226926600003 PM 15483270 ER PT J AU Feldweg, AM Lee, CW Matulonis, UA Castells, M AF Feldweg, AM Lee, CW Matulonis, UA Castells, M TI Rapid desensitization for hypersensitivity reactions to paclitaxel and docetaxel: a new standard protocol used in 77 successful treatments SO GYNECOLOGIC ONCOLOGY LA English DT Article DE paclitaxel and docetaxel hypersensitivity; desensitization ID CREMOPHOR-EL; MEDIATED REACTIONS; BREAST-CANCER; TAXOL; EXPERIENCE; TRIAL; CYCLOSPORINE; TOLERANCE; CARCINOMA; INFUSION AB Objective. Administration of paclitaxel is associated with hypersensitivity reactions (HSRs) in up to 9% of patients despite premedication. The purpose of this study was to evaluate the effectiveness of a standardized desensitization protocol in patients with HSRs to taxanes, based on our experience with carboplatin desensitization. Methods. We analyzed seventeen consecutive patients with documented HSRs to taxanes who required continued treatment with a taxane agent. The patients were treated with either paclitaxel or docetaxel using the 6- to 7-h standard desensitization protocol. Results. Seventeen patients who previously had severe taxane HSRs successfully completed 77 planned cycles of desensitization to paclitaxel or docetaxel, 72 of which were without reactions. Four patients developed HSRs during the desensitization protocol that were much less severe than their original HSRs and tolerated the re-administration of infusions without further reactions. Of these four patients, the first had palmar erythema 8 h after her 1st desensitization. The second patient had mild abdominal pain during her 1st cycle, and the third patient developed mild chest burning during her 2nd and 4th cycles. These three patients also completed subsequent desensitization cycles without reactions. The fourth patient developed a delayed urticaria reaction and gastrointestinal symptoms 6 h after completing her 1st desensitization. She elected to be treated with an alternative chemotherapy and did not receive additional courses of desensitization. Conclusion. The rapid standard desensitization protocol provides a safe and effective strategy for the re-administration of paclitaxel or docetaxel even after severe HSRs. (c) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Castells, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Rheumatol Immunol & Allergy, 1 Jimmy Fund Way,Smith Bldg Room 626D, Boston, MA 02115 USA. EM mcastells@partners.org NR 25 TC 66 Z9 72 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2005 VL 96 IS 3 BP 824 EP 829 DI 10.1016/j.ygyno.2004.11.043 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 906BN UT WOS:000227615600038 PM 15721432 ER PT J AU Liebson, E Rauch, P Graff, S Folstein, M AF Liebson, E Rauch, P Graff, S Folstein, M TI Early-onset dementia: Diagnostic considerations and implications for families SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID EARLY ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; COGNITIVE IMPAIRMENT; TEMPORAL VARIANT; BEHAVIOR; PREFERENCE; CARE C1 Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Canc Ctr Parenting Program, Boston, MA 02114 USA. Tufts Univ, Dept Psychiat, Medford, MA 02155 USA. Johns Hopkins Med Inst, Dept Psychiat, Baltimore, MD 21205 USA. RP Liebson, E (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. NR 26 TC 5 Z9 5 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2005 VL 13 IS 2 BP 102 EP 111 DI 10.1080/10673220590956492 PG 10 WC Psychiatry SC Psychiatry GA 932NR UT WOS:000229560900004 PM 16020024 ER PT J AU Betancourt, JR Green, AR Carrillo, JE Park, ER AF Betancourt, JR Green, AR Carrillo, JE Park, ER TI Cultural competence and health care disparities: Key perspectives and trends - Among stakeholders in managed care, government, and academe, cultural competence is emerging as an important strategy to address health care disparities SO HEALTH AFFAIRS LA English DT Article AB Cultural competence has gained attention as a potential strategy to improve quality and eliminate racial/ethnic disparities in health care. In 2002 we conducted interviews with experts in cultural competence from managed care, government, and academe to identify their perspectives on the field. We present our findings here and then identify recent trends in cultural competence focusing on health care policy, practice, and education. Our analysis reveals that many health care stakeholders are developing initiatives in cultural competence. Yet the motivations for advancing cultural competence and approaches taken vary depending on mission, goals, and sphere of influence. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Partners HealthCare Syst Inc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. New York Presbyterian Community Hlth Plan, New York, NY USA. Cornell Univ, Joan & Sanford Weill Med Coll, New York, NY 10021 USA. RP Betancourt, JR (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. EM jbetancourt@pol.net NR 26 TC 176 Z9 177 U1 3 U2 25 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR-APR PY 2005 VL 24 IS 2 BP 499 EP 505 DI 10.1377/hlthaff.24.2.499 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 909CE UT WOS:000227835700028 PM 15757936 ER PT J AU Fremont, AM Bierman, A Wickstrom, SL Bird, CE Shah, M Escarce, JJ Horstman, T Rector, T AF Fremont, AM Bierman, A Wickstrom, SL Bird, CE Shah, M Escarce, JJ Horstman, T Rector, T TI Use of geocoding in managed care settings to identify quality disparities - How indirect measures of race/ethnicity and socioeconomic status can be used by the nation's health plans to demonstrate disparities SO HEALTH AFFAIRS LA English DT Article; Proceedings Paper CT AcadrmyHealth Annual Meeting 2002 CY JUN, 2002 CL Washington, DC ID RACIAL VARIATION; ENROLLEES AB Tracking quality-of-care measures is essential for improving care, particularly for vulnerable populations. Although managed care plans routinely track quality measures, few examine whether their performance differs by enrollee race/ethnicity or socioeconomic status (SES), in part because plans do not collect that information. We show that plans can begin examining and targeting potential disparities using indirect measures of enrollee race/ethnicity and SES based on geocoding. Using such measures, we demonstrate disparities within both Medicare+Choice and commercial plans on Health Plan Employer Data and Information Set (HEDIS) measures of diabetes and cardiovascular care, including instances in which race/ethnicity and SES have distinct effects. C1 RAND Hlth, Santa Monica, CA USA. Univ Toronto, Toronto, ON, Canada. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Gen Internal Med, Westwood, CA USA. RP Fremont, AM (reprint author), RAND Hlth, Santa Monica, CA USA. EM fremont@rand.org RI Bird, Chloe/C-7107-2008 NR 12 TC 35 Z9 35 U1 1 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR-APR PY 2005 VL 24 IS 2 BP 516 EP 526 DI 10.1377/hlthaff.24.2.516 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 909CE UT WOS:000227835700031 PM 15757939 ER PT J AU Noel, P Frueh, BC Larme, AC Pugh, JA AF Noel, P Frueh, BC Larme, AC Pugh, JA TI Cottaborative care needs and preferences of primary care patients with muttimorbidity SO HEALTH EXPECTATIONS LA English DT Article DE chronic illness; collaborative care; multimorbidity; primary care; qualitative methods ID GENERAL-PRACTICE; DEPRESSIVE-DISORDERS; CHRONIC DISEASES; CHRONIC ILLNESS; MANAGEMENT; COMORBIDITY; MORBIDITY; QUALITY AB Objective To explore the collaborative care needs and preferences in primary care patients with multiple chronic illnesses. Design Focus groups utilizing a series of open-ended questions elicited self-identified problems, experiences in communicating with self-management needs, and preferences for monitoring providers, and follow-up. Responses were organized and interpreted in light of the essential elements of collaborative care for chronic illness. Setting and Participants Sixty patients having two or more chronic illnesses at eight geographically dispersed primary care clinics within the Veterans Health Administration in the United States. Results Identified problems included poor functioning, negative psychological reactions, negative effects on relationships and interference with work or leisure. Polypharmacy was a major concern. Problematic interactions with providers and the health care system were also mentioned, often in relation to specialty care and included incidents in which providers had ignored concerns or provided conflicting advice. Most participants, however, expressed overall satisfaction with their care and appreciation of their primary care physicians. Knowledge and skills deficits interfered with self-management. Participants were willing to use technology for monitoring or educational purposes if it did not preclude human contact, and were receptive to non-physician providers as long as they were used to augment, not eliminate, a physician's care. Conclusions Findings are consistent with the basic tenets of patient-centred, collaborative care, and suggested that health care can be organized and delivered to meet the complex needs of patients with multimorbidity. C1 Hlth Serv Res Ctr Excellence, VERDICT, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Noel, P (reprint author), Hlth Serv Res Ctr Excellence, VERDICT, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd,11C6, San Antonio, TX 78229 USA. EM pollyh@verdict.uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X NR 27 TC 59 Z9 59 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD MAR PY 2005 VL 8 IS 1 BP 54 EP 63 DI 10.1111/j.1369-7625.2004.00312.x PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 905VV UT WOS:000227599800007 PM 15713171 ER PT J AU Boudreaux, ED Kim, S Hohrmann, JL Clark, S Camargo, CA AF Boudreaux, ED Kim, S Hohrmann, JL Clark, S Camargo, CA TI Interest in smoking cessation among emergency department patients SO HEALTH PSYCHOLOGY LA English DT Article DE smoking; readiness to quit; emergency medicine ID CLINICAL PREVENTIVE SERVICES; REGULAR SOURCE; CARE; INTERVENTION; PHYSICIANS; SMOKERS; MEDICINE; ILLNESS; ABUSE AB The authors interviewed adult patients presenting to 4 Boston emergency departments (EDs) about their smoking, quit attempts, and interest in an outpatient referral. Of the 539 patients enrolled, 26% were current smokers. Of the current smokers, 72% had tried to quit in the past year, and 34% wanted an outpatient referral. Current smokers were younger than nonsmokers and were less likely to have a high school education, primary care provider, and private insurance. The findings of this study reinforce the potential benefit of routine screening for smoking and interest in quitting in the ED. Because many underinsured Americans use the ED as a source of regular health care, the public health implications of increasing screening, counseling, and referral for smokers are substantial. C1 Cooper Univ Hosp, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Newark, NJ 07103 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Med Sch, Cambridge, MA 02138 USA. RP Boudreaux, ED (reprint author), Cooper Univ Hosp, 1 Cooper Plaza, Camden, NJ 08103 USA. EM boudreaux-edwin@cooperhealth.edu OI Boudreaux, Edwin/0000-0002-3223-6371 FU NHLBI NIH HHS [R01- HL-03533]; NIDA NIH HHS [DA-016698-01]; NIEHS NIH HHS [T32 ES07069] NR 32 TC 18 Z9 18 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAR PY 2005 VL 24 IS 2 BP 220 EP 224 DI 10.1037/0278-6133.24.2.220 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA 905UE UT WOS:000227595000011 PM 15755236 ER PT J AU Newton-Cheh, C Larson, MG Corey, DC Benjamin, EJ Herbert, AG Levy, D D'Agostino, RB O'Donnell, CJ AF Newton-Cheh, C Larson, MG Corey, DC Benjamin, EJ Herbert, AG Levy, D D'Agostino, RB O'Donnell, CJ TI QT interval is a heritable quantitative trait with evidence of linkage to chromosome 3 in a genome-wide linkage analysis: The Framingham Heart Study SO HEART RHYTHM LA English DT Article; Proceedings Paper CT 54th Annual Fall Conference and Scientific Sessions of the American-Heart-Association Council for High Pressure Research CY OCT 24-27, 2000 CL WASHINGTON, D.C. SP Amer Heart Assoc DE genetics; QT interval; electrocardiography; long QT syndrome; arrthythmia; cohort study ID CARDIOVASCULAR MORTALITY; HYPERTENSIVE PATIENTS; CARDIAC-ARRHYTHMIA; TWINS; RISK; ELECTROCARDIOGRAM; POPULATION; DISEASE; REPOLARIZATION; VARIABILITY AB OBJECTIVES To identify genomic regions linked to QT interval duration in an unselected population. BACKGROUND QT interval prolongation is associated with increased risk of sudden cardiac death and coronary heart disease and may result from acquired conditions or inherited ion channel defects. The influence of genetic variants on QT interval length in apparently healthy individuals is uncertain. METHODS We studied subjects from the Framingham Heart Study in whom 12-lead ECGs were available from regular clinic examinations. QT, QT-peak, and RR intervals were measured using digital calipers. A 10-centiMorgan (cM) density genome-wide scan was performed in a subset of the largest families having at least two members with ECG phenotypes (326 families). Variance components methods (Genehunter) were used. RESULTS Evidence was observed for significant heritability of the QT interval (h(2) 0.35; 95% CI, 0.29-0.41), QT-peak interval (h(2) 0.37; 95% CI, 0.29-0.45), and calculated JT interval (h(2) 0.25; 95% CI, 0.19 - 0.31). In the genome-wide linkage analysis, we found suggestive evidence for linkage of the QT interval 19 to 48 cM from the tip of the short arm of chromosome 3 (maximum two-point LOD score 3.00, maximum multipoint LOD score 2.71). After fine-mapping with seven microsatellite markers, the peak multipoint LOD score rose to 2.84 at 24.4 cM. The region of linkage contains potassium and sodium channel genes, including the SCN5A gene, which has been implicated in one form of the long QT syndrome and in the Brugada syndrome. CONCLUSIONS QT and related ECG intervals are heritable traits in a large unselected population. We provide suggestive evidence for a quantitative trait locus on chromosome 3 influencing QT interval duration. Further studies are warranted to identify genes that influence QT interval variation and to determine the role of heritable factors in life-threatening QT prolongation. C1 NHLBI, Framinigham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Hosp, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. Boston Univ, Sch Med, Epidemiol & Prevent Med Sect, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framinigham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM codonnell@nih.gov OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1U01 HL 66582, HL07575] NR 41 TC 76 Z9 76 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2005 VL 2 IS 3 BP 277 EP 284 DI 10.1016/j.hrthm.2004.11.009 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 904LQ UT WOS:000227500000012 PM 15851319 ER PT J AU Rothman, AL Morishima, C Bonkovsky, HL Polyak, SJ Ray, R Di Bisceglie, AM Lindsay, KL Malet, PF Chang, M Gretch, DR Sullivan, DG Bhan, AK Wright, EC Koziel, MJ AF Rothman, AL Morishima, C Bonkovsky, HL Polyak, SJ Ray, R Di Bisceglie, AM Lindsay, KL Malet, PF Chang, M Gretch, DR Sullivan, DG Bhan, AK Wright, EC Koziel, MJ CA HALT-C Trial Grp TI Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C SO HEPATOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; VIRUS-INFECTION; IMMUNE-RESPONSES; PSEUDOTYPE VIRUS; RNA LEVELS; HCV; CELLS; NEUTRALIZATION; GLYCOPROTEINS; REPLICATION AB The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-Q on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CIL NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT, HCV RNA level, HCV genotype, and hepatic histopathology. LP, CEL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P =.03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed. C1 Univ Massachusetts, Sch Med, CIDVR, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Gen Clin Res Ctr, Farmington, CT USA. St Louis Univ, Sch Med, Div Infect Dis, St Louis, MO USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. Univ So Calif, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Div Gastroenterol, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Res Inst, Watertown, MA 02172 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Rothman, AL (reprint author), Univ Massachusetts, Sch Med, CIDVR, Rm S5-326,55 Lake Ave N, Worcester, MA 01655 USA. EM alan.rothman@umassmed.edu RI Polyak, Stephen/B-5743-2011 FU NCRR NIH HHS [M01 RR00043, RR00633]; NIDDK NIH HHS [DK92321, DK92324, DK92325, DK92326, DK92328, N01 DK92318] NR 39 TC 31 Z9 33 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2005 VL 41 IS 3 BP 617 EP 625 DI 10.1002/hep.20581 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 901QY UT WOS:000227298200026 PM 15726656 ER PT J AU Kamegaya, Y Hiasa, Y Zukerberg, L Fowler, N Blackard, JT Lin, WY Choe, WH Schmidt, EV Chung, RT AF Kamegaya, Y Hiasa, Y Zukerberg, L Fowler, N Blackard, JT Lin, WY Choe, WH Schmidt, EV Chung, RT TI Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis SO HEPATOLOGY LA English DT Article ID TRANSGENIC MICE; CORE PROTEIN; HEPATOCELLULAR-CARCINOMA; STRUCTURAL PROTEINS; EXPRESSION; STEATOSIS AB We developed hepatitis C virus (HCV) core-E1-E2 and HCV core transgenic mice on a common genetic background to assess the contribution of HCV structural proteins to hepatocarcinogenesis. Eight-week-old core-E1-E2, core, and nontransgenic mice inbred on the FVB X C57Bl/6 background were treated with diethylnitrosamine (DEN) and sacrificed at 32 weeks old. Proliferation and apoptosis were assessed by immunohistochemistry. The effect of viral proteins on apoptosis was evaluated in HepG2 cells in which apoptosis was induced by anti-Fas antibody. HCCs were identified at 32 weeks in the majority of DEN-treated mice from all three groups. The mean size of HCCs was significantly larger in core-E1-E2 transgenic (4.63 +/- 1.48 mm), compared with core transgenic (0.78 +/- 0.26 mm, P =.01), and nontransgenic (1.0 +/- 0.19 mm, P =.002) mice. While there were no differences in proliferation, the apoptotic index in core-E1-E2 transgenic HCCs was significantly lower than those found in core and non-transgenic HCCs. Core-E1-E2 transfected HepG2 cells demonstrated a significantly lower apoptotic index (0.35 +/- 0. 11) compared with that of core transfected cells (0.74 +/- 0.07, P =.0103). Analysis of a Fas-induced apoptosis model in HCV transgenic mice confirmed that core-E1-E2 transgenic liver underwent significantly less apoptosis than transgenic tissue expressing core only. In conclusion, HCV core-E1-E2 transgenic mice develop significantly larger tumors than transgenic mice expressing core alone or nontransgenic mice. The accelerated tumor phenotype is attributable to suppression of apoptosis rather than enhanced proliferation. These data implicate HCV E1 and/or E2 in conjunction with core as antiapoptotic, tumor accelerator proteins. C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, GRJ 825, Boston, MA 02114 USA. EM eschmidt@partners.org; rtchung@partners.org FU NIDDK NIH HHS [DK57857] NR 19 TC 39 Z9 41 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2005 VL 41 IS 3 BP 660 EP 667 DI 10.1002/hep.20621 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 901QY UT WOS:000227298200031 PM 15723444 ER PT J AU Leoncini, L Delsol, G Gascoyne, RD Harris, NL Pileri, SA Piris, MA Stein, H AF Leoncini, L Delsol, G Gascoyne, RD Harris, NL Pileri, SA Piris, MA Stein, H TI Aggressive B-cell lymphomas: a review based on the workshop of the XI Meeting of the European Association for Haematopathology SO HISTOPATHOLOGY LA English DT Review DE aggressive B-cell lymphoma; clinics; lymphoma classification; molecular biology; morphology; phenotype ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PREDOMINANT HODGKINS-DISEASE; FOLLICULAR LYMPHOMA; LYMPHOBLASTIC LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; MOLECULAR DIAGNOSIS; HETEROGENEOUS GROUP; OUTCOME PREDICTION; CASTLEMAN-DISEASE; VIRUS INFECTION AB The generic term aggressive B-cell lymphoma includes a variety of entities, each with particular diagnostic and therapeutic issues. To define these entities better and to help confront such issues, a workshop was organized by the European Association of Haematopathology (EAHP) and the Society of Haematology during the XI Meeting of the EAHP, held in Italy in May 2002. Participants were asked to submit cases under various categories and all cases submitted were examined and reviewed by the panel members. The panel's diagnoses formed the basis for discussion at the workshop and a limited number of cases were selected to be presented in more detail and discussed during the workshop. After the workshop the panel met again to discuss the outcome, summarized in this report, which describes the panel's proposals regarding diagnostic criteria, terminology, the definition of new entities and evaluation of biological differential and new prognostic parameters. C1 Univ Siena, Nuovo Policlin Le Scotte, Dipartimento Patol Umana & Oncol, I-53100 Siena, Italy. CHU Purpan, Anat Pathol Lab, Toulouse, France. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Policlin S Orsola, Ist Ematol & Oncol Med L&A Seragnoli, Cattedra Anat Patol, Bologna, Italy. Ctr Nacl Invest Oncol, Programa Patol Mol, Madrid, Spain. Free Univ Berlin, Univ Hosp Benjamin Franklin, Inst Pathol, D-1000 Berlin, Germany. RP Leoncini, L (reprint author), Univ Siena, Nuovo Policlin Le Scotte, Dipartimento Patol Umana & Oncol, Via Scotte 6, I-53100 Siena, Italy. EM leoncinil@unisi.it OI Piris, Miguel A/0000-0001-5839-3634 NR 75 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD MAR PY 2005 VL 46 IS 3 BP 241 EP 255 DI 10.1111/j.1365-2559.2005.02068.x PG 15 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 899GW UT WOS:000227133900001 PM 15720410 ER PT J AU Lim, HJ Gordon, NH Justice, AC AF Lim, HJ Gordon, NH Justice, AC TI Evaluation of multiple failure time analyses of observational data in patients treated for HIV SO HIV CLINICAL TRIALS LA English DT Article DE HIV/AIDS; multiple failures; observational data; treatment sequences ID ZIDOVUDINE COMBINATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; REGRESSION-ANALYSIS; PLUS LAMIVUDINE; STAVUDINE; DIDANOSINE; MONOTHERAPY; INFECTION; EFFICACY; SAFETY AB The development of protease inhibitors and nonnucleoside reverse transcriptase inhibitors has substantially increased the number of combinations available for multi-drug therapies in human immunodeficiency virus (HIV) infection. Unfortunately, all antiretroviral therapies lose efficacy over time or induce side effects, thus making secondary and tertiary alternatives necessary. With the multiplicity of multi-drug combination therapies, the challenge is to determine which multi-drug combination to use as initial therapy and which to use as subsequent therapy to maximize survival. No standard methodologic approach has been developed to answer this question within the context of observational clinical HIV data. We demonstrate the use of semi-parametric models employing repeated, multiple failure time analysis to compare the relative efficacy of treatments containing zidovudine, stavudine, or other multi-drug combinations for patients in the CHORUS (Collaborations in HIV Outcomes Research - US) database. C1 Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Serv Res, Pittsburgh, PA USA. RP Lim, HJ (reprint author), Med Coll Wisconsin, Div Biostat, 8701 Water Plank, Milwaukee, WI 53226 USA. EM hyun@mcw.edu NR 19 TC 2 Z9 2 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAR-APR PY 2005 VL 6 IS 2 BP 81 EP 91 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 943CU UT WOS:000230330500003 PM 15983892 ER PT J AU Napadow, V Makris, N Liu, J Kettner, NW Kwong, KK Hui, KKS AF Napadow, V Makris, N Liu, J Kettner, NW Kwong, KK Hui, KKS TI Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI SO HUMAN BRAIN MAPPING LA English DT Article DE acupuncture methods; current frequencies; human brain mapping; limbic system; electro-acupuncture ID POSITRON-EMISSION-TOMOGRAPHY; SOMATOSENSORY CORTEX; SENSORY STIMULATION; FUNCTIONAL MRI; DEFAULT MODE; PAIN; ACTIVATION; ANALGESIA; RATS; MECHANISMS AB The goal of this functional magnetic resonance imaging (fMRI) study was to compare the central effects of electroacupuncture at different frequencies with traditional Chinese manual acupuncture. Although not as time-tested as manual acupuncture, electroacupuncture does have the advantage of setting stimulation frequency and intensity objectively and quantifiably. Manual acupuncture, electroacupuncture at 2 Hz and 100 Hz, and tactile control stimulation were carried out at acupoint ST-36. Overall, electroacupuncture (particularly at low frequency) produced more widespread fMRI signal increase than manual acupuncture did, and all acupuncture stimulations produced more widespread responses than did our placebo-like tactile control stimulation. Acupuncture produced hemodynamic signal increase in the anterior insula, and decrease in limbic and paralimbic structures including the amygdala, anterior hippocampus, and the cortices of the subgenual and retrosplenial cingulate, ventromedial prefrontal cortex, frontal, and temporal poles, results not seen for tactile control stimulation. Only electroacupuncture produced significant signal increase in the anterior middle cingulate cortex, whereas 2-Hz electroacupuncture produced signal increase in the pontine raphe area. All forms of stimulation (acupuncture and control) produced signal increase in SII. These findings support a hypothesis that the limbic system is central to acupuncture effect regardless of specific acupuncture modality, although some differences do exist in the underlying neurobiologic mechanisms for these modalities, and may aid in optimizing their future usage in clinical applications. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Hui, KKS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM hui@nmr.mgh.harvard.edu FU NCCIH NIH HHS [R21 AT00978-A02, P01 AT002048-01]; NCRR NIH HHS [P41RR14075] NR 70 TC 166 Z9 185 U1 1 U2 23 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAR PY 2005 VL 24 IS 3 BP 193 EP 205 DI 10.1002/hbm.20081 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 900YQ UT WOS:000227250600005 PM 15499576 ER PT J AU Howlett, NG Taniguchi, T Durkin, SG D'Andrea, AD Glover, TW AF Howlett, NG Taniguchi, T Durkin, SG D'Andrea, AD Glover, TW TI The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability SO HUMAN MOLECULAR GENETICS LA English DT Article ID NUCLEAR-COMPLEX; DAMAGE RESPONSE; FANCD2; UBIQUITIN; PROTEIN; BRCA2; RECOMBINATION; INHIBITION; PCNA; SUMO AB Fanconi anemia (FA) is a rare multi-genic, autosomal and X-linked recessive disorder characterized by hematological abnormalities, developmental defects and increased cancer susceptibility. Patient-derived FA cells display heightened sensitivity to DNA cross-linking agents such as mitomycin C (MMC). In response to DNA damaging agents, and during S-phase of the cell cycle, the FA pathway is activated via the mono-ubiquitination of FANCD2 (FANCD2-Ub), signaling its translocation to discrete nuclear foci, where it co-localizes with the central DNA repair proteins BRCA1 and RAD51. However, the exact function of activated FANCD2-Ub remains unclear. Here, we have characterized the role of the FA pathway in response to DNA replicative stress by aphidicolin (APH) and hydroxyurea (HU). The FA pathway is strongly activated in response to both agents. In addition, using patient-derived FA cell lines and siRNA targeting FANCD2, we demonstrate a functional requirement for the FA pathway in response to low doses of APH: a replicative stress treatment known to result in chromosome breakage at common fragile sites. Both the total number of chromosome gaps and breaks and breaks at the specific common fragile sites FRA3B and FRA16D were significantly elevated in the absence of an intact FA pathway. Furthermore, we demonstrate that APH activates the mono-ubiquitination of both FANCD2 and PCNA and the phosphorylation of RPA2, signaling processive DNA replication arrest. Following APH treatment, FANCD2-Ub co-localizes with PCNA (early) and RPA2 (late) in discrete nuclear foci. Our results demonstrate an integral role for the FA pathway in the DNA replication stress response. C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Howlett, NG (reprint author), Univ Michigan, Dept Human Genet, 4909 Buhl,Box 0618,1241 E Catherine St, Ann Arbor, MI 48109 USA. EM niallg@umich.edu FU NCI NIH HHS [R01CA43222]; NHLBI NIH HHS [R01HL52725, P01HL54785]; NIDDK NIH HHS [R01DK43889]; NIGMS NIH HHS [T32 GM007544] NR 32 TC 152 Z9 156 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2005 VL 14 IS 5 BP 693 EP 701 DI 10.1093/hmg/ddi065 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 899EY UT WOS:000227128900013 PM 15661754 ER PT J AU Rollins, KE Kleinschmidt-DeMasters, BK Corboy, JR Damek, DM Filley, CM AF Rollins, KE Kleinschmidt-DeMasters, BK Corboy, JR Damek, DM Filley, CM TI Lymphomatosis cerebri as a cause of white matter dementia SO HUMAN PATHOLOGY LA English DT Article DE primary central nervous system lymphoma; white matter; dementia; immunocompetent; magnetic resonance imaging ID CENTRAL-NERVOUS-SYSTEM; RAPIDLY PROGRESSIVE DEMENTIA; PRIMARY MALIGNANT-LYMPHOMA; CNS LYMPHOMA; BRAIN; FEATURES; CT; AIDS AB Primary central nervous system lymphoma most often presents as a solitary, isolated lesion in immunocompetent patients. Rarely, the disease presents as a diffuse, infiltrating condition without formation of a cohesive mass, a pattern called lymphomatosis cerebri. We present 3 immunocompetent individuals who developed rapidly progressive dementia. Magnetic resonance imaging features mimicked other disorders of white matter and prompted preoperative diagnoses of Binswanger's disease (subcortical ischemic vascular dementia), unknown leukoencephalopathy, viral infection, or infiltrating glioma. Neuropathologic examination at biopsy (Poon T, Matoso I, Tchertkoff V, Weitzner I Jr, Gade M. CT features of primary cerebral lymphoma in AIDS and non-AIDS patients. J Comput Assist Tomogr. 1989;13:6-9) and autopsy (Schwaighofer BW, Hesselink JR, Press GA, Wolf RL, Healy ME, Berthoty DP. Primary intracranial CNS lymphoma: MR manifestations. Am J Neuroradiol. 1993;10:725-9) demonstrated nonnecrotic, diffusely infiltrating, large-cell B-cell lymphoma of white matter, with relative sparing of gray matter, and without significant leptomeningeal involvement or bulky periventricular disease at autopsy. Microglial and astrocytic reactions, but only subtle myelin pallor, were evident as individual tumor cells permeated the entire brain and spinal cord, albeit with considerable variation in cell density. Individual tumor cells Could be identified from the optic nerve to spinal cord, documenting the "whole-brain" nature of the disease. CD20 immunostaining was necessary to fully appreciate the extent of individual lymphoma cell percolation through the white matter. The neurobehavioral deficits manifested by these patients demonstrate that lymphomatosis cerebri is an additional neoplastic cause of white matter dementia and can be added to the growing list of disorders responsible for this syndrome. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Sch Med, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Neurosurg, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO 80220 USA. RP Kleinschmidt-DeMasters, BK (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pathol, Sch Med, Box B-216, Denver, CO 80262 USA. EM bk.demasters@uchsc.edu NR 39 TC 42 Z9 43 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2005 VL 36 IS 3 BP 282 EP 290 DI 10.1016/j.humpath.2005.01.014 PG 9 WC Pathology SC Pathology GA 915DR UT WOS:000228278400009 PM 15791573 ER PT J AU Duty, SM Calafat, AM Silva, MJ Ryan, L Hauser, R AF Duty, SM Calafat, AM Silva, MJ Ryan, L Hauser, R TI Phthalate exposure and reproductive hormones in adult men SO HUMAN REPRODUCTION LA English DT Article DE environmental; epidemiology; hormones; human; phthalates ID SEXUAL-DIFFERENTIATION; MALE-RATS; DIETHYLHEXYL PHTHALATE; QUANTITATIVE DETECTION; INHIBIN-B; METABOLITES; TESTOSTERONE; MALFORMATIONS; POPULATION; PARAMETERS AB BACKGROUND: Phthalates are used in personal and consumer products, food packaging materials, and polyvinyl chloride plastics and have been measured in the majority of the general population of the USA. Consistent experimental evidence shows that some phthalates are developmental and reproductive toxicants in animals. This study explored the association between environmental levels of phthalates and altered reproductive hormone levels in adult men. METHODS: Between 1999 and 2003, 295 men were recruited from Massachusetts General Hospital. Selected phthalate metabolites were measured in urine. Linear regression models explored the relationship between specific gravity-adjusted urinary phthalate monoester concentrations and serum levels of reproductive hormones, including FSH, LH, sex hormone-binding globulin, testosterone, and inhibin B. RESULTS: An interquartile range (IQR) change in monobenzyl phthalate (MBzP) exposure was significantly associated with a 10% [95% confidence interval (CI): -16, -4.0] decrease in FSH concentration. Additionally, an IQR change in monobutyl phthalate (MBP) exposure was associated with a 4.8% (95% CI: 0, 10) increase in inhibin B but this was of borderline significance. CONCLUSIONS: Although we found associations between MBP and MBzP urinary concentrations and altered levels of inhibin B and FSH, the hormone concentrations did not change in the expected patterns. Therefore, it is unclear whether these associations represent physiologically relevant alterations in these hormones, or whether they represent associations found as a result of conducting multiple comparisons. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Simmons Coll, Sch Hlth Studies, Dept Nursing, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIEHS NIH HHS [ES00002, ES09718, T32 ES07069] NR 32 TC 105 Z9 108 U1 7 U2 27 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAR PY 2005 VL 20 IS 3 BP 604 EP 610 DI 10.1093/humrep/deh656 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 899FC UT WOS:000227129300006 PM 15591081 ER PT J AU Oh, WY Yun, SH Tearney, GJ Bouma, BE AF Oh, WY Yun, SH Tearney, GJ Bouma, BE TI Wide tuning range wavelength-swept laser with two semiconductor optical amplifiers SO IEEE PHOTONICS TECHNOLOGY LETTERS LA English DT Article DE optical filters; semiconductor lasers; semiconductor optical amplifiers (SOAs); tunable lasers ID FREQUENCY-DOMAIN REFLECTOMETRY; DOPED FIBER LASER; COHERENCE TOMOGRAPHY; CAVITY; FILTER; POWER AB We demonstrate a wide tuning range high-speed wavelength-swept semiconductor laser based on a polygon scanning filter that is common to two laser cavities. Linear wavelength tuning was achieved over 145 nm around 1310 nm at a tuning repetition rate of 20 kHz. The wavelength tuning filter is expandable to accommodate multiple semiconductor optical amplifiers for further widening of the laser wavelength tuning range. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Oh, WY (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM woh1@partners.org RI Oh, Wang-Yuhl/C-2055-2011 FU NCI NIH HHS [R01 CA103769, R01 CA103769-03] NR 17 TC 28 Z9 28 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1041-1135 J9 IEEE PHOTONIC TECH L JI IEEE Photonics Technol. Lett. PD MAR PY 2005 VL 17 IS 3 BP 678 EP 680 DI 10.1109/LPT.2004.841003 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 899IP UT WOS:000227138400054 PM 20651947 ER PT J AU Nappi, J Frimmel, H Yoshida, H AF Nappi, J Frimmel, H Yoshida, H TI Virtual endoscopic visualization of the colon by shape-scale signatures. SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE computed tomographic colonography (CTC); computer-aided analysis; image shape analysis; virtual colonoscopy; visualization ID COMPUTER-AIDED DIAGNOSIS; CT COLONOGRAPHY; TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; POLYPS; COLONOSCOPY; SCHEME; IMAGES; PERFORMANCE AB We developed a new visualization method for virtual endoscopic examination of computed tomographic (CT) colonographic data by use of shape-scale analysis. The method provides each colonic structure of interest with a unique color, thereby facilitating rapid diagnosis of the colon. Two shape features, called the local shape index and curvedness, are used for defining the shape-scale spectrum. When we map the shape index and curvedness values within CT colonographic data to the shape-scale spectrum, specific types of colonic structures are represented by unique characteristic signatures in the spectrum. The characteristic signatures of specific types of lesions can be determined by use of computer-simulated lesions or by use of clinical data sets subjected to a computerized detection scheme. The signatures are used for defining a two-dimensional color map by assignment of a unique color to each signature region. The method was evaluated visually by use of computer-simulated lesions and clinical CT colonographic data sets, as well as by an evaluation of the human observer performance in the detection of polyps without and with the use of the color maps. The results indicate that the coloring of the colon yielded by the shape-scale color maps can be used for differentiating among the chosen colonic structures. Moreover, the results indicate that the use of the shape-scale color maps can improve the performance of radiologists in the detection of polyps in CT colonography. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. RP Nappi, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. EM jnappi@partners.org; Yoshida.Hito@mrg.harvard.edu FU NCI NIH HHS [CA095279] NR 40 TC 10 Z9 11 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD MAR PY 2005 VL 9 IS 1 BP 120 EP 131 DI 10.1109/TITB.2004.837834 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 906WU UT WOS:000227676200014 PM 15787014 ER PT J AU Freedman, D Radke, RJ Zhang, T Jeong, Y Lovelock, DM Chen, GTY AF Freedman, D Radke, RJ Zhang, T Jeong, Y Lovelock, DM Chen, GTY TI Model-based segmentation of medical imagery by matching distributions SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE deformable segmentation; image-guided therapy; medical image segmentation; prostate cancer; prostate segmentation; shape and appearance model ID GEODESIC ACTIVE CONTOURS; NONLINEAR DIMENSIONALITY REDUCTION; ULTRASOUND IMAGES; DEFORMABLE MODEL; PROSTATE; TRACKING; VARIABILITY; INFORMATION; FRAMEWORK; OBJECTS AB The segmentation of deformable objects from three-dimensional (3-D) images is an important and challenging problem, especially in the context of medical imagery. We present a new segmentation algorithm based on matching probability distributions of photometric variables that incorporates learned shape and appearance models for the objects of interest. The main innovation over similar approaches is that there is no need to compute a pixelwise correspondence between the model and the image. This allows for a fast, principled algorithm. We present promising results on difficult imagery for 3-D computed tomography images of the male pelvis for the purpose of image-guided radiotherapy of the prostate. C1 Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA. Rensselaer Polytech Inst, Dept Comp Sci, Troy, NY 12180 USA. Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Radiat Oncol & Radiat Therapy, Boston, MA 02114 USA. RP Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, 110 8th St, Troy, NY 12180 USA. EM freedman@cs.rpi.edu; rjradke@ecse.rpi.edu; zhangt3@cs.rpi.edu; jeongy@rpi.edu; lovelocm@mskcc.org; gchen@partners.org RI Radke, Richard/I-3289-2013 OI Radke, Richard/0000-0001-5064-7775 NR 39 TC 92 Z9 93 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2005 VL 24 IS 3 BP 281 EP 292 DI 10.1109/TMI.2004.841228 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 901CH UT WOS:000227260100001 PM 15754979 ER PT J AU Feuerer, M Benoist, C Mathis, D AF Feuerer, M Benoist, C Mathis, D TI Green T-R cells SO IMMUNITY LA English DT Editorial Material ID IMMUNOLOGICAL SELF-TOLERANCE; REGULATORY CELLS; FOXP3 AB Identification of the transcription factor Foxp3 as a "master regulator" of regulatory T (T-R) cells was a major discovery. A new study by Fontenot et al. (2005), reported in this issue of Immunity, provides novel insights into T-R cell biology by tracking their behavior in mice expressing a GFP-Foxp3 fusion-protein reporter. C1 Harvard Univ, Sch Med,Sect Immunol & Immunogenet, Brigham & Womens Hosp, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. RP Feuerer, M (reprint author), Harvard Univ, Sch Med,Sect Immunol & Immunogenet, Brigham & Womens Hosp, Joslin Diabet Ctr,Dept Med, 1 Joslin Pl, Boston, MA 02215 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2005 VL 22 IS 3 BP 271 EP 272 DI 10.1016/j.immuni.2005.03.002 PG 2 WC Immunology SC Immunology GA 912UP UT WOS:000228105700001 PM 15780983 ER PT J AU Martinvalet, D Zhu, PC Lieberman, J AF Martinvalet, D Zhu, PC Lieberman, J TI Granzyme A induces caspase-independent mitochondrial damage, a required first step for apoptosis SO IMMUNITY LA English DT Article ID CYTOCHROME-C RELEASE; SERINE-PROTEASE OMI/HTRA2; FAS-MEDIATED APOPTOSIS; CELL-DEATH; PERMEABILITY TRANSITION; SUPEROXIDE-DISMUTASE; DNA FRAGMENTATION; ENDONUCLEASE-G; ACTIVATION; INDUCTION AB Granzyme A (GzmA) triggers cell death with apoptotic features by targeting the endoplasmic reticulum-associated SET complex, which contains the GzmA-activated DNase NM23-H1, its inhibitor SET, and Ape1. The SET complex was postulated to translocate to the nucleus in response to oxidative stress and participate in its repair. Because mitochondrial damage is important in apoptosis, we investigated whether GzmA damages mitochondria. GzmA induces a rapid increase in reactive oxygen species and mitochondrial transmembrane potential loss, but does not cleave bid or cause apoptogenic factor release. The mitochondrial effect is direct, does not require cytosol, and is insensitive to bcl-2 and caspase inhibition. SET complex nuclear translocation, which occurs within minutes of peroxide or GzmA treatment, is dependent on superoxide generation since superoxide scavengers block it. Superoxide scavengers also block apoptosis by CTLs expressing GzmA and/or GzmB. Therefore, mitochondrial damage is an essential first step in killer cell granule-mediated pathways of apoptosis. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI45587] NR 58 TC 155 Z9 158 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2005 VL 22 IS 3 BP 355 EP 370 DI 10.1016/j.immuni.2005.02.004 PG 16 WC Immunology SC Immunology GA 912UP UT WOS:000228105700010 PM 15780992 ER PT J AU Zucchelli, S Holler, P Yamagata, T Roy, M Benoist, C Mathis, D AF Zucchelli, S Holler, P Yamagata, T Roy, M Benoist, C Mathis, D TI Defective central tolerance induction in NOD mice: Genomics and genetics SO IMMUNITY LA English DT Article ID NONOBESE DIABETIC MICE; STEROID-RECEPTOR NUR77; REGULATORY T-CELLS; SELECTION IN-VIVO; NEGATIVE SELECTION; ADAPTER PROTEIN; PEPTIDE LIGANDS; THYMOCYTES; APOPTOSIS; ANTIGEN AB The genetic determinism of type-1 diabetes in NOD mice likely involves complementary defects in central T cell tolerance induction and peripheral immunoregulation. To study the contribution of the NOD genetic background to central tolerance, we followed the behavior of BDC2.5 clonotype thymocytes in fetal thymic organ cultures (FTOC). The NOD genetic background encodes a quantitative deficiency in the ability to delete these self-reactive thymocytes and to divert them to the CD8 alpha alpha lineage. In genetic analyses, comparing NOD and B6.H2(g7) FTOCs, the NOD defect incorporated the influence of several loci (notably ones on chr1 and 3). Microarray analyses assessing FTOCs from the same two strains argued that the NOD abnormality reflects the combined effects of turning down the gene expression program that provokes apoptosis and turning on a new program promoting cell survival. Intersection of the data from the two approaches points to a small set of attractive candidate genes. C1 Harvard Univ, Sch Med,Sect Immunol & Immunogenet, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med,Sect Immunol & Immunogenet, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu NR 48 TC 117 Z9 121 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2005 VL 22 IS 3 BP 385 EP 396 DI 10.1016/j.immuni.2005.01.015 PG 12 WC Immunology SC Immunology GA 912UP UT WOS:000228105700012 PM 15780994 ER PT J AU Haake, DA Matsunaga, J AF Haake, DA Matsunaga, J TI Leptospiral membrane proteins - variations on a theme? Commentary SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Editorial Material ID OUTER-MEMBRANE; INTERROGANS; SURFACE C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Haake, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu FU NIAID NIH HHS [R01 AI034431-08, R01 AI034431] NR 16 TC 4 Z9 6 U1 0 U2 0 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD MAR PY 2005 VL 121 IS 3 BP 143 EP 145 PG 3 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 915UV UT WOS:000228337700003 PM 15802754 ER PT J AU Callahan, MV Hamer, DH AF Callahan, MV Hamer, DH TI On the medical edge: Preparation of expatriates, refugee and disaster relief workers, and peace corps volunteers SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID TERM MALARIA PROPHYLAXIS; TRAVELERS; ATOVAQUONE/PROGUANIL; SCHISTOSOMIASIS; PRIMAQUINE AB Travelers to medically remote areas require special pretravel evaluation and environmentally specific education. Using a case-based format, this article provides information on approaches to the predeployment medical, dental, and psychologic preparation of long-term travelers and expeditions to extreme environments. C1 Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. Boston Univ, Sch Publ Hlth, Ctr Int Hlth & Dev, Boston, MA 02118 USA. Tufts Univ, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA 02111 USA. RP Callahan, MV (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 65 Landsdowne St,Suite 200, Cambridge, MA 02139 USA. EM MVCallahan@partners.org OI Hamer, Davidson/0000-0002-4700-1495 NR 18 TC 7 Z9 7 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2005 VL 19 IS 1 BP 85 EP + DI 10.1016/j.idc.2004.10.010 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 903TO UT WOS:000227448700007 PM 15701548 ER PT J AU Farabaugh, A Mischoulon, D Fava, M Wu, SL Mascarini, A Tossani, E Alpert, JE AF Farabaugh, A Mischoulon, D Fava, M Wu, SL Mascarini, A Tossani, E Alpert, JE TI The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE depression; Hamilton Rating Scale for Depression (HAMD-17); treatment outcome ID MAJOR DEPRESSION; FLUOXETINE TREATMENT; PATTERN-ANALYSIS; PLACEBO; METAANALYSIS; MIRTAZAPINE; IMPROVEMENT; PAROXETINE; SCALE; ONSET AB The 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety/Somatization factor includes six items: Anxiety (psychic), Anxiety (somatic), Somatic Symptoms (gastrointestinal), Somatic Symptoms (general), Hypochondriasis and Insight. This study examines the relationship between early changes (defined as those observed between baseline and week 1) in these HAMD-17 Anxiety/Somatization Factor items and treatment outcome among major depressive disorder (MDD) patients who participated in a study comparing the antidepressant efficacy of a standardized extract of hypericum with both placebo and fluoxetine. Following a 1-week, single-blind washout, patients with MDD diagnosed by the Structured Clinical Interview for DSM-IV (SCID) were randomized to 12 weeks of double-blind treatment with hypericum extract (900 mg/day), fluoxetine (20 mg/day) or placebo. The relationship between early changes in HAMD-17 anxiety/ somatization factor items and treatment outcome was assessed separately for patients who received study treatment (hypericum or fluoxetine) versus placebo with a logistic regression method. One hundred and thirty-five patients (female 57%, mean age = 37.3 +/- 11.0 years; mean baseline HAMD-17 = 19.7 +/- 3.2 years) were randomized to double-blind treatment and were included in the intent-to-treat (ITT) analyses. After adjusting for baseline HAMD-17 scores and for multiple comparisons with the Bonferroni correction, patients who remitted (HAMD-17 score < 8) after study treatment had significantly greater early improvement in Somatic Symptoms (General) scores than non-remitters. No other significant differences in early changes were noted for the remaining items between remitters versus non-remitters who received active treatment. For patients treated with placebo, early change was not predictive of remission for any of the items after Bonferroni correction. In conclusion, the presence of early improvement on the HAMD-17 item concerning fatigue and general somatic symptoms is significantly predictive of achieving remission at endpoint with active study treatment but not with placebo. (c) 2005 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Farabaugh, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM afarabaugh@partners.org OI Alpert, Jonathan/0000-0002-4332-908X; Tossani, Eliana/0000-0002-6197-4496 NR 19 TC 20 Z9 22 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAR PY 2005 VL 20 IS 2 BP 87 EP 91 DI 10.1097/00004850-200503000-00004 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 906IO UT WOS:000227634600004 PM 15729083 ER PT J AU Zhang, YJ Finegold, MJ Jin, YZ Wu, MX AF Zhang, YJ Finegold, MJ Jin, YZ Wu, MX TI Accelerated transition from the double-positive to single-positive thymocytes in G alpha i2-deficient mice SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE colitis; Gai2; positive selection; and TCR ID HOMEOSTASIS-DRIVEN PROLIFERATION; REGULATORY T-CELLS; PERTUSSIS-TOXIN; ALPHA-SUBUNITS; G-PROTEINS; SELECTION; COLITIS; RECEPTOR; THYMUS; TCR AB Deletion of alphai2 subunit of heterotrimeric G proteins induces a 2-4-fold increase in the proportions of CD4 and CD8 single-positive (SP) thymocytes as compared with wild-type littermates, but how Galphai2 is involved in thymocyte development is unknown. To determine a role for Galphai2 in a specific developmental stage of thymocyte differentiation, we studied the ontogeny of thymocytes in Galphai2-deficient mice. Our data show that an accelerated transition from the double-positive (DP) to SP thymocytes, rather than impairment in thymic emigration, accounts for a high proportion of the SP thymocytes in the absence of Galphai2. Lack of Galphai2 greatly augmented a response of thymocytes to TCR-mediated stimulation, as evidenced by enhanced proliferation of the DP thymocytes upon ligation of the TCRs. The augmented response may be the reason behind the expedited transition from the DP to SP thymocytes in the animal. In accordance with this, effects of Galphai2 deficiency on CD8 or CD4 SP thymocyte differentiation required engagement of the TCRs with either MHC class I or MHC class II molecule. The abnormal thymocyte development resulted in an increase in positive selection, altered usage of TCR Vbeta gene, aberrant development of CD4+CD25+ T regulatory cells and untimely thymic involution, the contribution of which to colitis development in the animal is discussed. These findings reveal a previously unappreciated role for Galphai2 protein in clonal selection and functionality of thymocytes. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Wu, MX (reprint author), Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. EM mwu2@partners.org FU NIAID NIH HHS [AI050822]; NIDDK NIH HHS [DK56338, DK43351] NR 54 TC 18 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2005 VL 17 IS 3 BP 233 EP 243 DI 10.1093/intimm/dxh204 PG 11 WC Immunology SC Immunology GA 900WB UT WOS:000227243900003 PM 15684040 ER PT J AU Suswam, EA Nabors, LB Huang, YY Yang, XH King, PH AF Suswam, EA Nabors, LB Huang, YY Yang, XH King, PH TI IL-1 beta induces stabilization of IL-8 mRNA in malignant breast cancer cells via the 3 ' untranslated region: Involvement of divergent RNA-binding factors HuR, KSRP and TIAR SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE posttranscriptional gene regulation; AU-rich element; HuR; KH-type splicing regulatory protein; T-cell inhibitor of apoptosis-related protein; breast cancer ID ACTIVATED PROTEIN-KINASE; AU-RICH ELEMENTS; INTERLEUKIN-8 GENE-EXPRESSION; MAMMALIAN STRESS GRANULES; TUMOR-NECROSIS-FACTOR; IN-VIVO; POSTTRANSCRIPTIONAL REGULATION; 3'-UNTRANSLATED REGION; STABILITY FACTOR; TNF-ALPHA AB IL-8 plays an integral role in promoting the malignant phenotype in breast cancer, and its production is directly influenced by inflammatory cytokines in the tumor microenvironment. Here, we show that activation of IL-1beta receptors on malignant HS578t and MDA-MB-231 breast cancer cells strongly induces IL-8 expression and that RNA stabilization is persistently activated at least 12-24 hr after stimulation. SB 203580 and rapamycin reversed the RNA stabilization effect of IL-1beta in a dose-dependent manner, suggesting involvement of the p38/MAP kinase and mTOR pathways. A luciferase reporter assay indicated that the stabilization effect was dependent on cis elements in the 3'-untranslated region (UTR) of the IL-8 transcript. By UV cross-linking, we identified multiple cellular factors that interact with the IL-8 3'UTR, ranging 34-76 kDa. Immunoprecipitation analysis indicated that HuR, KSRP and TIAR bound to one or more loci in the 3'UTR. While the cross-linking patterns were similar, quantitative immunoprecipitation of native IL-8 RNA from IL-1beta-stimulated cytoplasmic extract revealed a 20-fold greater association of transcript with the stabilizing factor HuR vs. the destabilizing factor KSRP. In conclusion, IL-1beta is a potent cytokine stimulus for IL-8 RNA stabilization in breast cancer cells, possibly by enhanced binding of cytoplasmic HuR to the 3'UTR. Published 2004 Wiley-Liss, Inc(dagger). C1 Birmingham Veterans Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Neurol, Birmingham, AL USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL USA. RP King, PH (reprint author), 1235 Jefferson Tower,625 S 19th St, Birmingham, AL 35294 USA. EM pking@uab.edu NR 58 TC 62 Z9 64 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2005 VL 113 IS 6 BP 911 EP 919 DI 10.1002/ijc.20675 PG 9 WC Oncology SC Oncology GA 888BD UT WOS:000226348300007 PM 15514971 ER PT J AU Papakostas, GI Petersen, T Iosifescu, DV Burns, AM Nierenberg, AA Alpert, JE Rosenbaum, JF Fava, M AF Papakostas, GI Petersen, T Iosifescu, DV Burns, AM Nierenberg, AA Alpert, JE Rosenbaum, JF Fava, M TI Obesity among outpatients with major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fluoxetine treatment; major depressive disorder; obesity ID OVERWEIGHT AB Studies focusing on the prevalence of obesity in major depressive disorder (MDD), or the impact of excess body fat on the treatment of MDD are lacking. The aim of the present work is to systematically study obesity in MDD outpatients. A total of 369 MDD outpatients enrolled in an 8-wk trial of 20 mg fluoxetine had height and weight measured at baseline. We then examined: (1) the prevalence of being overweight or obese, (2) the relationship between obesity and a number of demographic and clinical variables, and, (3) the relationship between relative body weight and obesity with clinical response. We found that more than 50% of patients were overweight [body mass index (BMI) >= 25 kg/m(2)], while 20% were obese (BMI >= 30 kg/m(2)). Obese patients presented with worse somatic well-being scores than non-obese MDD patients, but they did not differ with respect to depression severity, anxiety, somatic complaints, hopelessness or hostility. Greater relative body weight, but not obesity, predicted non-response. In conclusion, greater relative body weight was found to place MDD outpatients at risk for fluoxetine resistance. C1 Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Depress Clin & Res Program,Sch Med, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Depress Clin & Res Program,Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01-MH-48-483-05] NR 18 TC 36 Z9 36 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD MAR PY 2005 VL 8 IS 1 BP 59 EP 63 DI 10.1017/S1461156704004602 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 911VH UT WOS:000228033700007 PM 15361263 ER PT J AU Arterburn, DE Maciejewski, ML Tsevat, J AF Arterburn, DE Maciejewski, ML Tsevat, J TI Impact of morbid obesity on medical expenditures in adults SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE health services; economic; cost; overweight ID COST-EFFECTIVENESS; GASTRIC BYPASS; UNITED-STATES; BODY-WEIGHT; US ADULTS; SURGERY; OVERWEIGHT; BURDEN; TRENDS; RISK AB CONTEXT: Morbid obesity (body mass index (BMI) greater than or equal to40 kg/m(2)) is associated with substantially increased morbidity and mortality from chronic health conditions and with poorer health-related quality of life; however, less is known about the impact of morbid obesity on healthcare expenditures. OBJECTIVE: To examine the impact of morbid obesity on healthcare expenditures using a nationally representative sample of US adults. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional analysis of 16 262 adults from the 2000 Medical Expenditure Panel Survey, a nationally representative survey of the noninstitutionalized civilian population of the United States. Per capita healthcare expenditures were calculated for National Institutes of Health BMI categories, based on self-reported height and weight, using a two-part, multivariable model adjusted for age, gender, race, income, education level, type of health insurance, marital status, and smoking status. MAIN OUTCOME MEASURES: Odds of incurring any healthcare expenditure and per capita healthcare expenditures associated with morbid obesity in 2000. RESULTS: When compared with normal-weight adults, the odds of incurring any healthcare expenditure in 2000 were two-fold greater among adults with morbid obesity. Per capita healthcare expenditures for morbidly obese adults were 81% (95% confidence interval (CI): 48-121%) greater than normal-weight adults, 65% (95% CI: 37-110%) greater than overweight adults, and 47% (95% CI: 11-96%) greater than adults with class I obesity. Excess costs among morbidly obese adults resulted from greater expenditures for office-based visits, outpatient hospital care, in-patient care, and prescription drugs. Aggregate US healthcare expenditures associated with excess body weight among morbidly obese US adults exceeded $11 billion in 2000. CONCLUSIONS: The economic burden of morbid obesity among US adults is substantial. Further research is needed to identify interventions to reduce the incidence and prevalence of morbid obesity and improve the health and economic outcomes of morbidly obese adults. C1 Univ Cincinnati, Med Ctr, Dept Internal Med, Div Gen Internal Med,Sect Outcomes Res, Cincinnati, OH 45267 USA. Cincinnati Vet Affairs Med Ctr, Hlth Serv Res & Dev, Cincinnati, OH USA. Univ Cincinnati, Inst Hlth Policy & Hlth Serv Res, Cincinnati, OH 45267 USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Arterburn, DE (reprint author), Univ Cincinnati, Med Ctr, Dept Internal Med, Div Gen Internal Med,Sect Outcomes Res, POB 670840, Cincinnati, OH 45267 USA. EM david.arterburn@uc.edu NR 28 TC 118 Z9 118 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 2005 VL 29 IS 3 BP 334 EP 339 DI 10.1038/sj.ijo.0802896 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 897CK UT WOS:000226981400012 PM 15685247 ER PT J AU Jagsi, R Buck, DA Singh, AK Engleman, M Thakkar, V Frank, SJ Flynn, D AF Jagsi, R Buck, DA Singh, AK Engleman, M Thakkar, V Frank, SJ Flynn, D TI Results of the 2003 Association of Residents in Radiation Oncology (ARRO) surveys of residents and chief residents in the United States SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 19-23, 2003 CL Salt Lake City, UT SP Amer Soc Therapeut Radiol & Oncol DE Association of Residents in Radiation Oncology; ARRO; radiation oncology residency; resident training; survey ID TRAINING-PROGRAMS AB Purpose: To document demographic characteristics of current residents, career motivations and aspirations, and training program policies and resources. Methods: In 2003, the Association of Residents in Radiation Oncology (ARRO) conducted two nationwide surveys: one of all U.S. radiation oncology residents and one of chief residents. Results: The Chief Residents' Survey was completed by representatives from all 77 programs (response rate, 100%). The Residents' Survey was returned by 229 respondents (response rate, 44%). In each, 32% of respondents were female. The most popular career after residency was private practice (46%), followed by permanent academic practice (28%). Changes that would entice those choosing private practice to consider an academic career included more research experience as a resident (76%), higher likelihood of tenure (69%), lesser time commitment (66%), and higher salary (54%). Although the majority of respondents were satisfied with educational experience overall, a number of programs were reported to provide fewer resources than required. Conclusions: Median program resources and numbers of outliers are documented to allow residents and program directors to assess the relative adequacy of experience in their own programs. Policy-making bodies and individual programs should consider these results when developing interventions to improve educational experiences of residents and to increase retention of radiation oncologists in academic practice. (C) 2005 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. Univ Washington, Seattle, WA 98195 USA. Northwestern Univ, Chicago, IL 60611 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Holy Family Hosp, Methuen, MA USA. RP Jagsi, R (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. OI Jagsi, Reshma/0000-0001-6562-1228 NR 14 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2005 VL 61 IS 3 BP 642 EP 648 DI 10.1016/j.ijrobp.2004.07.690 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 898CG UT WOS:000227052900004 PM 15708241 ER PT J AU Wyss, C Dewhirst, FE Paster, BJ Thurnheer, T Luginbuhl, A AF Wyss, C Dewhirst, FE Paster, BJ Thurnheer, T Luginbuhl, A TI Guggenheimella bovis gen. nov., sp nov., isolated from lesions of bovine dermatitis digitalis SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID HUMAN PERIODONTITIS; ORAL SPIROCHETE; DAIRY-CATTLE; ACID; TREPONEMES; TREES; FLORA AB Dermatitis digitalis is an economically important ulcerative disease of undetermined aetiology affecting the hooves of cattle. Material was examined from two independent cases of this disease in Switzerland. Cultures from the advancing front of both lesions yielded large numbers of closely related short, mesophilic, non-motile, non-spore-forming, anaerobic, proteolytic, Gram-positive rods. The 16S rRNA gene sequences of strains OMZ 913(T) and OMZ 915 were identical and indicate Tindallia magadiensis and Eubacterium saphenum as their closest relatives. Phenotypically, the novel isolates are clearly distinguished from related bacteria by protein and antigen patterns, by cellular fatty acids and by API ZYM activities. The diamino acid of the Gram-positive cell wall is ornithine and the G + C content of OMZ 913(T) DNA is 44.4 mol%. The phylogenetic distance from recognized taxa in the phylum Firmicutes is sufficient to place these bovine isolates into a novel genus and species, for which the name Guggenheimella bovis gen. nov., sp. nov. is proposed, with OMZ 913(T) (=CIP 108087(T) =DSM 15657(T)) as the type strain. C1 Univ Zurich, Inst Orale Biol, Zentrum Zahn Mund & Kieferheilkunde, CH-8028 Zurich, Switzerland. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Tierarztpraxis, CH-3186 Dudingen, Switzerland. RP Wyss, C (reprint author), Univ Zurich, Inst Orale Biol, Zentrum Zahn Mund & Kieferheilkunde, Plattenstr 11, CH-8028 Zurich, Switzerland. EM wyss.c@zzmk.unizh.ch NR 31 TC 14 Z9 14 U1 0 U2 8 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD MAR PY 2005 VL 55 BP 667 EP 671 DI 10.1099/ijs.0.63116-0 PN 2 PG 5 WC Microbiology SC Microbiology GA 912QE UT WOS:000228093500017 PM 15774641 ER PT J AU Dolan, SE Grinspoon, S AF Dolan, SE Grinspoon, S TI Topic VII: What is the role of hormonal menopausal therapy in HIV-infected and at-risk women? Androgen deficiency and the role of testosterone administration in HIV-infected women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT Conference on Fertility Regulation and Systemic Hormones in HIV-infected and At-Risk Women CY JAN 13-15, 2003 CL McLean, VA SP NIH, Off AIDS Res, NICHD ID HUMAN-IMMUNODEFICIENCY-VIRUS; WEIGHT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dolan, SE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR PY 2005 VL 38 SU 1 BP S48 EP S49 DI 10.1097/01.qai.0000167050.19171.6f PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 927YO UT WOS:000229238500028 PM 15867625 ER PT J AU Sampson, HA Munoz-Furlong, A Bock, A Schmitt, M Bass, R Chowdhury, BA Decker, WW Furlong, TJ Galli, SJ Golden, DB Gruchalla, RS Harlor, AD Hepner, DL Howarth, M Kaplan, AP Levy, JH Lewis, LM Lieberman, PL Metcalfe, DD Murphy, R Pollart, SM Pumphrey, RS Rosenwasser, LJ Simons, FE Wood, JP Camargo, CA AF Sampson, HA Munoz-Furlong, A Bock, A Schmitt, M Bass, R Chowdhury, BA Decker, WW Furlong, TJ Galli, SJ Golden, DB Gruchalla, RS Harlor, AD Hepner, DL Howarth, M Kaplan, AP Levy, JH Lewis, LM Lieberman, PL Metcalfe, DD Murphy, R Pollart, SM Pumphrey, RS Rosenwasser, LJ Simons, FE Wood, JP Camargo, CA TI Symposium on the definition and management of anaphylaxis: Summary report SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE anaphylaxis; hypersensitivity; allergy; allergic reaction; insect sting; food allergy ID EXERCISE-INDUCED ANAPHYLAXIS; ALLERGIC REACTIONS; EPINEPHRINE ABSORPTION; VENOM IMMUNOTHERAPY; INSECT STINGS; CHILDREN; EMERGENCY; FOOD; EPIDEMIOLOGY; ADOLESCENTS C1 Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. Food Allergy& Anaphylaxis Network, Fairfax, VA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA USA. Cent Manchester Healthcare Natl Hlth Serv Trust H, Manchester, Lancs, England. Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sampson, HA (reprint author), Mt Sinai Sch Med, Dept Pediat, Box 1198,1 Gustave L Levy Pl, New York, NY 10029 USA. EM hugh.sampson@mssm.edu NR 55 TC 218 Z9 226 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2005 VL 115 IS 3 BP 584 EP 591 DI 10.1016/j.jaci.2005.01.008 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 907AN UT WOS:000227687000023 PM 15753908 ER PT J AU Bartsch, P Mairbaurl, H Maggiorini, M Swenson, ER AF Bartsch, P Mairbaurl, H Maggiorini, M Swenson, ER TI Physiological aspects of high-altitude pulmonary edema SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE pulmonary artery pressure; hypoxic pulmonary vasoconstriction; nitric oxide; inflammation; alveolar fluid clearance; pathophysiology; review ID ACUTE MOUNTAIN-SICKNESS; ISOLATED RAT LUNGS; TRANSEPITHELIAL SODIUM-TRANSPORT; INDUCED PERMEABILITY INCREASES; ALVEOLAR EPITHELIAL-CELLS; I/D GENE POLYMORPHISM; NITRIC-OXIDE SYNTHASE; BRONCHOALVEOLAR LAVAGE; VASCULAR-RESISTANCE; DIFFUSING-CAPACITY AB High-altitude pulmonary edema ( HAPE) develops in rapidly ascending nonacclimatized healthy individuals at altitudes above 3,000 m. An excessive rise in pulmonary artery pressure ( PAP) preceding edema formation is the crucial pathophysiological factor because drugs that lower PAP prevent HAPE. Measurements of nitric oxide ( NO) in exhaled air, of nitrites and nitrates in bronchoalveolar lavage (BAL) fluid, and forearm NO-dependent endothelial function all point to a reduced NO availability in hypoxia as a major cause of the excessive hypoxic PAP rise in HAPE-susceptible individuals. Studies using right heart catheterization or BAL in incipient HAPE have demonstrated that edema is caused by an increased microvascular hydrostatic pressure in the presence of normal left atrial pressure, resulting in leakage of large-molecular-weight proteins and erythrocytes across the alveolarcapillary barrier in the absence of any evidence of inflammation. These studies confirm in humans that high capillary pressure induces a high-permeability-type lung edema in the absence of inflammation, a concept first introduced under the term "stress failure." Recent studies using microspheres in swine and magnetic resonance imaging in humans strongly support the concept and primacy of nonuniform hypoxic arteriolar vasoconstriction to explain how hypoxic pulmonary vasoconstriction occurring predominantly at the arteriolar level can cause leakage. This compelling but as yet unproven mechanism predicts that edema occurs in areas of high blood flow due to lesser vasoconstriction. The combination of high flow at higher pressure results in pressures, which exceed the structural and dynamic capacity of the alveolar capillary barrier to maintain normal alveolar fluid balance. C1 Med Univ Hosp Heidelberg, Div Sports Med, Dept Internal Med, D-69120 Heidelberg, Germany. Med Clin, Dept Cardiol, Zurich, Switzerland. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bartsch, P (reprint author), Med Univ Hosp Heidelberg, Div Sports Med, Dept Internal Med 6, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM peter_bartsch@med.uni-heidelberg.de NR 123 TC 153 Z9 161 U1 1 U2 21 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2005 VL 98 IS 3 BP 1101 EP 1110 DI 10.1152/japplphysiol.01167.2004 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 895LG UT WOS:000226863100045 PM 15703168 ER PT J AU Zhang, XK Watson, DK AF Zhang, XK Watson, DK TI The FLI-1 transcription factor is a short-lived phosphoprotein in T cells SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE FLI-1-1 transcription factor; phosphatase 2A; phosphoprotein; protein kinase; T cell activation ID DNA-BINDING; ETS FAMILY; PROTEIN-KINASE; RENAL-DISEASE; PHOSPHORYLATION; GENE; ACTIVATION; EXPRESSION; MEMBER; GENERATION AB The FLI-1 transcription factor is a member of the ETS gene family, most closely related to ERG. In this study, the FLI-1 protein products were characterized using a specific monoclonal antibody previously developed against bacterially expressed protein. In the human T-cell line Jurkat, both isoforms of FLI-1, p51 and p48, are phosphorylated, primarily on serine residues. FLI-1 phosphorylation is increased by a Ca2+-mediated process, and inhibitor studies indicate that protein phosphatase 2A, at least in part, controls FLI-1 phosphorylation level. FLI-1 phosphorylation is not stimulated by phorbal 12-myristate 13-acetate (PMA), a protein kinase C activator, and in this it differs from ERG protein phosphorylation. The p51 isoform has a half-life of 105 min, and p48 has a half-life of 80 min; in contrast, the ERG protein is much more stable with a half-life of 21 h. Newly synthesized FLI-1 protein decreased during human T cell activation. Our data suggest that although the FLI-1 and ERG genes are highly homologous, their distinct properties may contribute to their different roles in gene regulation. C1 Ralph H Johnson VAMC, Med Res Serv, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Dept Pathol & Lab Med, Charleston, SC 29425 USA. Hollings Canc Ctr, Charleston, SC 29425 USA. RP Zhang, XK (reprint author), Ralph H Johnson VAMC, Med Res Serv, Dept Med, Div Rheumatol & Immunol, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU NCI NIH HHS [P01 CA78582] NR 41 TC 13 Z9 13 U1 0 U2 1 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM JI J. Biochem. PD MAR PY 2005 VL 137 IS 3 BP 297 EP 302 DI 10.1093/jb/mvi032 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 922KI UT WOS:000228836400007 PM 15809330 ER PT J AU Chang, SK Mirabal, YN Atkinson, EN Cox, D Malpica, A Follen, M Richards-Kortum, R AF Chang, SK Mirabal, YN Atkinson, EN Cox, D Malpica, A Follen, M Richards-Kortum, R TI Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence; reflectance; tissues; biomedical optics; neoplasia; cervix; in vivo diagnosis ID LASER-INDUCED FLUORESCENCE; EXCITATION WAVELENGTHS; CONFOCAL MICROSCOPY; OPTICAL-PROPERTIES; LIGHT-SCATTERING; TISSUE; CANCER; NEOPLASIA; DIAGNOSIS; SPECTRA AB Optical technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide improved point-of-care detection methods for cervical neoplasia that are sensitive, specific, and cost-effective. Our specific goals are to analyze the diagnostic potential of reflectance and fluorescence spectra, alone and in combination, to discriminate normal and precancerous cervical tissue in vivo and to identify which classification features contain significant diagnostic information. Reflectance spectra are measured at four source-detector separations and fluorescence emission spectra are measured at 16 excitation wavelengths, from 324 sites in 161 patients. These 20 spectral features are permuted in all possible combinations of one, two, and three; and classification algorithms are developed to evaluate the diagnostic performance of each combination. Algorithms based on fluorescence spectra alone yield better diagnostic performance than those based on reflectance spectra alone. The combination of fluorescence and reflectance do not significantly improve diagnostic performance compared to fluorescence alone, except in the case of discriminating high-grade precancers from columnar normal tissue. In general, fluorescence emission spectra at 330- to 360-nm and 460- to 470-nm excitation provide the best diagnostic performance for separating all pairs of tissue categories. (c) 2005 Society of Photo-Optical Instrumentation Engineers. C1 Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Austin, TX 78712 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Austin, TX 78712 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Austin, TX 78712 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Rice Univ, Dept Stat, Houston, TX 77030 USA. RP Richards-Kortum, R (reprint author), Univ Texas, Biomed Engn Program, ENS 610, Dept Biomed Engn, Austin, TX 78712 USA. EM kortum@mail.utexas.edu RI Richards-Kortum, Rebecca/P-4074-2014 OI Richards-Kortum, Rebecca/0000-0003-2347-9467 FU NCI NIH HHS [P01-CA82710] NR 28 TC 80 Z9 81 U1 0 U2 14 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2005 VL 10 IS 2 AR 024031 DI 10.1117/1.1899686 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 974CZ UT WOS:000232570200030 PM 15910104 ER PT J AU Zhang, Q Brukilacchio, TJ Li, A Stott, JJ Chaves, T Hillman, E Wu, T Chorlton, M Rafferty, E Moore, RH Kopans, DB Boas, DA AF Zhang, Q Brukilacchio, TJ Li, A Stott, JJ Chaves, T Hillman, E Wu, T Chorlton, M Rafferty, E Moore, RH Kopans, DB Boas, DA TI Coregistered tomographic x-ray and optical breast imaging: initial results SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE breast imaging; optical tomography; tomosynthesis; optical spectroscopy; breast cancer; multimodality imaging ID IN-VIVO; INDOCYANINE GREEN; MAMMOGRAPHY; SPECTROSCOPY; CANCER; RECONSTRUCTION; TUMORS; LIGHT; MRI; ABSORPTION AB We describe what is, to the best of our knowledge, the first pilot study of coregistered tomographic x-ray and optical breast imaging. The purpose of this pilot study is to develop both hardware and data processing algorithms for a multimodality imaging method that provides information that neither x-ray nor diffuse optical tomography (DOT) can provide alone. We present in detail the instrumentation and algorithms developed for this multimodality imaging. We also present results from our initial pilot clinical tests. These results demonstrate that strictly coregistered x-ray and optical images enable a detailed comparison of the two images. This comparison will ultimately lead to a better understanding of the relationship between the functional contrast afforded by optical imaging and the structural contrast provided by x-ray imaging. (c) 2005 Society ofPhoto-Optical Instrumentation Engineers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Breast Imaging Unit, Boston, MA 02129 USA. Tufts Univ, Dept Phys, Medford, MA 02155 USA. Innovat Opt Inc, Woburn, MA 01801 USA. RP Zhang, Q (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, 135th St,Bldg 149,Room 2301, Boston, MA 02129 USA. EM qzhang@nmr.mgn.harvard.edu RI Hillman, Elizabeth/B-9854-2009 NR 59 TC 96 Z9 98 U1 0 U2 2 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2005 VL 10 IS 2 AR 024033 DI 10.1117/1.1899183 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 974CZ UT WOS:000232570200032 PM 15910106 ER PT J AU Giannoudis, PV Da Costa, AA Raman, R Mohamed, AK Smith, RM AF Giannoudis, PV Da Costa, AA Raman, R Mohamed, AK Smith, RM TI Double-crush syndrome after acetabular fractures - A sign of poor prognosis SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Article ID TERM FOLLOW-UP; SCIATIC NERVE; HIP; INJURY AB Injury to the sciatic nerve is one of the more serious complications of acetabular fracture and traumatic dislocation of the hip, both in the short and long term. We have reviewed prospectively patients, treated in our unit, for acetabular fractures who had concomitant injury to the sciatic nerve, with the aim of predicting the functional outcome after these injuries. Of 136 patients who underwent stabilisation of acetabular fractures, there were 27 (19.9%) with neurological injury. At initial presentation, 13 patients had a complete foot-drop, ten had weakness of the foot and four had burning pain and altered sensation over the dorsum of the foot. Serial electromyography (EMG) studies were performed and the degree of functional recovery was monitored using the grading system of the Medical Research Council. In nine patients with a foot-drop, there was evidence of a proximal acetabular (sciatic) and a distal knee (neck of fibula) nerve lesion, the double-crush syndrome. At the final follow-up, clinical examination and EMG studies showed full recovery in five of the ten patients with initial muscle weakness, and complete resolution in all four patients with sensory symptoms (burning pain and hyperaesthesia). There was improvement of functional capacity (motor and sensory) in two patients who presented initially with complete foot-drop. In the remaining 11 with foot-drop at presentation, including all,nine with the double-crush lesion, there was no improvement in function at a mean follow-up of 4.3 years. C1 St James Univ Hosp, Dept Neurophysiol, Leeds LS9 7TF, W Yorkshire, England. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02144 USA. RP Giannoudis, PV (reprint author), St James Univ Hosp, Dept Neurophysiol, Beckett St, Leeds LS9 7TF, W Yorkshire, England. EM pgiannoudi@aol.com NR 28 TC 7 Z9 10 U1 0 U2 1 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 0301-620X J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD MAR PY 2005 VL 87B IS 3 BP 401 EP 407 DI 10.1302/0301-620X.87B3 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 907IA UT WOS:000227708700023 PM 15773653 ER PT J AU Ton, FN Gunawardene, SC Lee, H Neer, RM AF Ton, FN Gunawardene, SC Lee, H Neer, RM TI Effects of low-dose prednisone on bone metabolism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE clinical trials; corticosteroids; corticosteroid osteoporosis; bone turnover markers; bone metabolism ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; RHEUMATOID-ARTHRITIS; CORTICOSTEROID OSTEOPOROSIS; ORAL CORTICOSTEROIDS; MINERAL DENSITY; THERAPY; TURNOVER; FRACTURE; MARKERS; SERUM AB Prednisone 5 mg/day suppresses multiple indices of bone formation in a randomized placebocontrolled trial in healthy postmenopausal females. This suggests that even low doses of prednisone may reduce bone repair or renewal and may have adverse effects on bone mass and/or bone strength. Introduction: High doses of chronic glucocorticoids are known to have adverse effects on bone, and measures to prevent bone loss are well established for doses >7.5 mg daily, because these doses can cause premature or exaggerated osteoporosis. However, it is unclear if chronic prednisone doses of 5 mg daily have the same effects on bone. There are no established recommendations for preventing glucocorticoid-induced osteoporosis in people taking prednisone 5 mg daily, a dose used frequently in medical practice to treat diseases of the lungs, joints, skin, muscles, eyes, nerves, etc. Our primary objective was to test whether prednisone 5 mg daily affects serum and urine indices of bone metabolism in healthy postmenopausal women. Our secondary objectives were to determine if prednisone 5 mg affected systolic or diastolic blood pressure or causes side effects. Materials and Methods: A double-blinded randomized placebo-controlled 8-week trial in 50 healthy postmenopausal women was conducted at the Massachusetts General Hospital Outpatient General Clinical Research Center. Patients were randomly assigned to prednisone 5 mg daily or matching placebo for 6 weeks, followed by a 2-week recovery phase. Markers of bone formation and resorption were determined at weeks 0, 2, 4, 6, and 8. Indices of osteoblast activity included serum propeptide of type I N-terminal procollagen (PINP), propeptide of type I C-terminal procollagen (PICP), osteocalcin, and bone-specific alkaline phosphatase (BSALP). Indices of osteoclast activity included urine and serum type I collagen N-telopeptide (NTX) and free urinary deoxypyridinoline (DPD). Results and Conclusions: Prednisone rapidly and significantly decreased serum PINP (p < 0.01), PICP (p < 0.01), and osteocalcin (p < 0.01) and free urinary deoxypyridinoline (p = 0.017). These changes were largely reversed during the recovery period. Side effects were indistinguishable in the two groups. Neither systolic nor diastolic blood pressure changed significantly throughout the study between the two groups. In conclusion, low-dose prednisone significantly decreases indices of bone formation and may decrease indices of bone resorption in postmenopausal women. Further studies are needed to assess the effects of low-dose prednisone on BMD and fracture risk. C1 Massachusetts Gen Hosp, Endocrinol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Rheumatol Allergy & Immunol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Ton, FN (reprint author), Massachusetts Gen Hosp, Endocrinol Unit, Bulfinch 315,55 Fruit St, Boston, MA 02114 USA. EM fton@bidmc.harvard.edu FU NCRR NIH HHS [M01-RR-01066] NR 25 TC 85 Z9 90 U1 1 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2005 VL 20 IS 3 BP 464 EP 470 DI 10.1359/JBMR.041125 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 898TB UT WOS:000227098000011 PM 15746991 ER PT J AU Hansen, KE Binkley, N Christian, R Vallarta-Ast, N Krueger, D Drezner, MK Blank, RD AF Hansen, KE Binkley, N Christian, R Vallarta-Ast, N Krueger, D Drezner, MK Blank, RD TI Interobserver reproducibility of criteria for vertebral body exclusion SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE aging; epidemiology; evidence/guidelines; osteoporosis; quantitation; bone densitometry ID BONE-MINERAL DENSITY; QUANTITATIVE COMPUTED-TOMOGRAPHY; PREDICT HIP FRACTURE; X-RAY ABSORPTIOMETRY; ELDERLY-WOMEN; POPULATION; ULTRASOUND; RISK; OSTEOPOROSIS; OSTEOPENIA AB We studied reproducibility of the ISCD vertebral exclusion criteria among four interpreters. Surprisingly, agreement among interpreters was only moderate, because of differences in threshold for diagnosing focal structural defects and choice of which vertebra among a pair discordant for T-score, area, or BMC to exclude. Our results suggest that reproducibility may be improved by specifically addressing the sources of interobserver disagreement. Introduction: Although DXA is widely used to measure vertebral BNID, its interpretation is subject to multiple confounders including osteoarthritis, aortic calcification, and scoliosis. In an attempt to standardize interpretation and minimize the impact of artifacts, the International Society for Clinical Densitometry (ISCD) established criteria for vertebral exclusion, including the presence of a focal structural defect (FSD), discrepancy of >1 SD in T-score between adjacent vertebrae, and a lack of increase in BMC or area from L, to L, Whereas the efforts of the ISCD represent an important advance in BMD interpretation, the interobserver reproducibility with application of these criteria is unknown. We hypothesized that there would be substantial agreement among four interpreters regarding application of the exclusion criteria and the final lumbar spine T-score. Materials and Methods: Each interpreter read a set of 200 lumbar DXA scans obtained on male veterans, applying the ISCD vertebral body exclusion criteria. Results: Surprisingly, agreement among interpreters was only moderate. Differences in interpretation resulted from differing thresholds for recognition of FSD and the choice of excluding the upper or lower vertebral body for the criteria requiring comparison between adjacent vertebrae. Conclusions: Despite their apparent simplicity, the ISCD vertebral exclusion criteria are difficult to apply consistently. In principle, appropriate refinement of the exclusion criteria may significantly improve interobserver agreement. C1 Univ Wisconsin, Hosp & Clin, William S Middleton Mem Vet Hosp, Dept Med,Rheumatol Sect, Madison, WI 53792 USA. Univ Wisconsin, Osteoporosis Clin Ctr, Madison, WI 53792 USA. Univ Wisconsin, Res Program, Madison, WI 53792 USA. Univ Wisconsin, Dept Med, Endocrinol Diabet & Metab Sect, Madison, WI 53792 USA. Univ Wisconsin, Dept Med, Geriatr Sect, Madison, WI 53792 USA. Univ Wisconsin, Dept Radiol, William S Middleton Mem Vet Hosp, Madison, WI 53792 USA. Univ Wisconsin, Geriatr Res Educ & Clin Ctr, William S Middleton Mem Vet Hosp, Madison, WI 53792 USA. RP Hansen, KE (reprint author), Univ Wisconsin, Hosp & Clin, William S Middleton Mem Vet Hosp, Dept Med,Rheumatol Sect, Mailbox 3244,600 Highland Ave, Madison, WI 53792 USA. EM keh@medicine.wisc.edu OI Blank, Robert Daniel/0000-0003-2950-1944 FU NCRR NIH HHS [1K12RR017614-01, 1K12RR017614-1]; NIAMS NIH HHS [R01 AR27032-33]; NIDDK NIH HHS [R01 DK58363-01]; PHS HHS [R01 SK 65830-1] NR 19 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2005 VL 20 IS 3 BP 501 EP 508 DI 10.1359/JBMR.041134 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 898TB UT WOS:000227098000016 PM 15746996 ER PT J AU Stroud, RE Deschamps, AM Lowry, AS Hardin, AE Mukherjee, R Lindsey, ML Ramamoorthy, S Zile, MR Spencer, WH Spinale, FG AF Stroud, RE Deschamps, AM Lowry, AS Hardin, AE Mukherjee, R Lindsey, ML Ramamoorthy, S Zile, MR Spencer, WH Spinale, FG TI Plasma monitoring of the myocardial specific tissue inhibitor of metalloproteinase-4 after alcohol septal ablation in hypertrophic obstructive cardiomyopathy SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE hypertrophy; TIMP-4; HOCM; alcohol-induced myocardial infarction ID FAILING HUMAN HEART; MATRIX-METALLOPROTEINASES; REDUCTION THERAPY; EXPRESSION; FAILURE; GLYCOSYLATION; INFARCTION; SUPPORT; SYSTEM; TIMP-4 AB Background: The overall goal of this study was to develop an assay procedure for measuring the relative abundance of tissue inhibitor of metalloproteinase (TIMP)-4 in plasma, and then use this approach to determine dynamic changes of TIMP-4 levels in hypertrophic obstructive carchomyopathic (HOCM) patients after an acute myocardial infarction (MI). Matrix metalloproteinases (MMPs) contribute to tissue remodeling and are regulated by the endogenous TIMPs. TIMP-4 is observed to be expressed in higher abundance in the myocardium when compared with other types of tissues. Recent clinical studies have measured changes in TIMP-4 levels; however, these studies have been limited to measuring this protein from myocardial tissue samples. To date, no studies have monitored TIMP-4 levels in plasma samples. Methods and Results: Plasma TIMP-4 levels were examined (by semiquantitative immunoblotting) in normal (n = 18) and HOCM (n = 16) patients after alcohol-induced MI. Serial measurements of plasma TIMP-4 levels were examined up to 60 hours after alcohol-induced MI in patients with HOCM. Unglycosylated plasma TIMP-4 levels increased 250% in the HOCM patients when compared with normal controls. Total plasma TIMP-4 levels decreased by 20% at 30 hours after alcohol-induced MI. Conclusions: The unique results demonstrated that an induction of a controlled MI, specifically through alcohol ablation, caused a reduction in plasma TIMP-4 levels in HOCM patients after alcohol-induced MI that would facilitate myocardial remodeling in the early post-MI setting. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA. Ralph H Johnson Vet Assoc Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Bldg,114 Doughty St,Room 625, Charleston, SC 29403 USA. RI Lindsey, Merry/B-2650-2012; OI Deschamps, Anne/0000-0001-7415-1408 FU NCRR NIH HHS [M01-RR01070]; NHLBI NIH HHS [HL-45024, HL-97012, R01 HL075360] NR 32 TC 14 Z9 14 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD MAR PY 2005 VL 11 IS 2 BP 124 EP 130 DI 10.1016/j.cardfail.2004.05.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 907AW UT WOS:000227688100008 PM 15732032 ER PT J AU Androudi, S Ahmed, M Fiore, T Brazitikos, P Foster, CS AF Androudi, S Ahmed, M Fiore, T Brazitikos, P Foster, CS TI Combined pars plana vitrectomy and phacoemulsification to restore visual acuity in patients with chronic uveitis SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID INTRAOCULAR-LENS IMPLANTATION; CATARACT-EXTRACTION; DIABETIC-PATIENTS; MACULAR HOLES; LENSECTOMY; MANAGEMENT; SURGERY; EYES AB Purpose: To report the outcomes of combined phacoemulsification and pars plana vitrectomy (PPV) to restore visual acuity in patients with cataract and posterior segment involvement secondary to chronic uveitis. Setting: Ocular Immunology and Uveitis Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. Methods: This study comprised 34 patients (20 women, 14 men; 36 eyes) with posterior segment involvement secondary to chronic uveitis who had combined phacoemulsification and PPV from 1998 to 2002. The main outcome measures were visual acuity, intraocular pressure, and cystoid macular edema. Results: The mean patient age was 45 years +/- 16.09 (SD). The mean duration of uveitis before surgery was 56 +/- 44.17 months. In 24 eyes (66.7%), an intraocular lens (IOL) was implanted during surgery; 12 eyes (33.3%) were left aphakic. Five eyes (13.8%) received an intraocular steroid injection intraoperatively. Visual acuity improved in 26 eyes (72.2%), deteriorated in 5 (13.9%), and was unchanged in 5 (13.9%). The main reason for decreased visual acuity was refractory macular edema. During the follow-up, 2 IOLs were explanted secondary to lens intolerance. One IOL was repositioned because of iris capture by the haptics, and 1 dislocated inferiorly, causing monocular diplopia. The mean follow-up was 23.4 +/- 16.7 months. Conclusions: Results indicate that combined phacoemulsification and PPV is a feasible technique for the removal of cataract and pathologic vitreous in eyes with chronic uveitis. Although the exact role of vitrectomy in patients with uveitis remains to be determined, the combined surgery successfully restored useful vision in most cases. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 28 TC 33 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD MAR PY 2005 VL 31 IS 3 BP 472 EP 478 DI 10.1016/j.jcrs.2004.06.040 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 917VD UT WOS:000228496400011 PM 15811733 ER PT J AU Hofer, AM AF Hofer, AM TI Another dimension to calcium signaling: a look at extracellular calcium SO JOURNAL OF CELL SCIENCE LA English DT Article DE parathyroid extracellular-Ca2+-sensing receptor (CaR); hemichannels; ASIC; endocytosis; Notch; plant Ca2+ sensor (CAS) ID METABOTROPIC GLUTAMATE RECEPTORS; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; SENSING RECEPTOR; CA2+-SENSING RECEPTOR; INTERCELLULAR COMMUNICATION; SYNAPTIC-TRANSMISSION; NERVE-TERMINALS; CATION CHANNEL; CELL-SURFACE AB Cell biologists know the calcium ion best as a vital intracellular second messenger that governs countless cellular functions. However, the recent identification of cell-surface detectors for extracellular Ca2+ has prompted consideration of whether Ca2+ also functions as a signaling molecule in the extracellular milieu. The cast of Ca2+ sensors includes the well-characterized extracellular-Ca2+ sensing receptor, a G-protein-coupled receptor originally isolated from the parathyroid gland. In addition, other receptors, channels and membrane proteins, such as gap junction hemichannels, metabotropic glutamate receptors, HERG K+ channels and the receptor Notch, are all sensitive to external [Ca2+] fluctuations. A recently cloned Ca2+ sensor (CAS) in Arabidopsis extends this concept to the plant kingdom. Emerging evidence indicates that [Ca2+] in the local microenvironment outside the cell undergoes alterations potentially sufficient to exert biological actions through these sensor proteins. The extracellular space might therefore constitute a much more dynamic Ca2+ signaling compartment than previously appreciated. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Surg, Boston, MA 02132 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02132 USA. RP Hofer, AM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Surg, 1400 VFW Pkwy, Boston, MA 02132 USA. EM ahofer@rics.bwh.harvard.edu NR 78 TC 50 Z9 52 U1 2 U2 13 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR 1 PY 2005 VL 118 IS 5 BP 855 EP 862 DI 10.1242/jcs.01705 PG 8 WC Cell Biology SC Cell Biology GA 916IK UT WOS:000228378400003 PM 15731003 ER PT J AU Mashour, GA Peterfreund, RA AF Mashour, GA Peterfreund, RA TI Spinal anesthesia and Ogilvie's syndrome SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE Ogilvie's syndrome; pseudoobstruction; ileus; spinal anesthesia; regional anesthesia ID PSEUDOOBSTRUCTION AB Ogilvie's syndrome is an uncommon disorder of acute colonic pseudoobstruction that is often associated with concomitant medical disease or psychiatric medication. Therapeutic interventions include cholinesterase inhibitors, colonic decompression, and, in severe cases, surgery. We report a case of functional obstruction that was resolved after spinal anesthesia. The effect of spinal anesthesia on the autonomic control of colonic motility is discussed, and the literature on neuraxial blockade and Ogilvie's syndrome is reviewed. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM rpeterfreund@partners.org NR 8 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAR PY 2005 VL 17 IS 2 BP 122 EP 123 DI 10.1016/j.jclinane.2004.03.015 PG 2 WC Anesthesiology SC Anesthesiology GA 920AW UT WOS:000228660400008 PM 15809128 ER PT J AU Mashour, GA Sunder, N Acquadro, MA AF Mashour, GA Sunder, N Acquadro, MA TI Anesthetic management of Turner syndrome: a systematic approach SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE airway management : anomalies; genetic disorders; mental retardation; micrognathia; Turner syndrome ID ADULTHOOD AB Turner syndrome is a complex and common genetic disorder that affects women and is associated with a wide variety of anatomic and physiological disorders. These abnormalities, especially those relating to the airway and cardiovascular system, pose a challenge to the anesthesiologist. We report a case of Turner syndrome associated with mental retardation and difficult airway, followed by a discussion of the perioperative management and review of the relevant literature. We also provide a concise tabular summary of the many problems associated with Turner syndrome and give guidelines for a systematic perioperative approach. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mashour, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM gmashour@partners.org NR 6 TC 3 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 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAR PY 2005 VL 17 IS 2 BP 128 EP 130 DI 10.1016/j.jclinane.2004.06.010 PG 3 WC Anesthesiology SC Anesthesiology GA 920AW UT WOS:000228660400010 PM 15809130 ER PT J AU Pitteloud, N Acierno, JS Meysing, AU Dwyer, AA Hayes, FJ Crowley, WF AF Pitteloud, N Acierno, JS Meysing, AU Dwyer, AA Hayes, FJ Crowley, WF TI Reversible Kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FIBROBLAST-GROWTH-FACTOR; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; LUTEINIZING-HORMONE; MEDIAN-EMINENCE; X-CHROMOSOME; RECEPTOR; NEURONS; CELLS; EXPRESSION AB Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder. Recently, loss-of-function mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been shown to cause autosomal dominant KS. To date, the detailed reproductive phenotype of KS associated with mutations in the FGFR1 has yet to be described. We report a kindred comprising a male proband with KS and spontaneous reversibility, whose mother had delayed puberty and whose maternal grandfather isolated anosmia. The proband presented at age 18 yr with KS and was subsequently treated with testosterone ( T) therapy. Upon discontinuation of T therapy, he recovered from his hypogonadotropic hypogonadism, as evidenced by a normal LH secretion pattern, sustained normal serum T levels, and active spermatogenesis. The three members of this single family harbor the same FGFR1 mutation (Arg(622)X) in the tyrosine kinase domain. This report demonstrates 1) the first genetic cause of the rare variant of reversible KS, 2) the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and 3) a loss of function mutation in the FGFR1 gene causing delayed puberty. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Bartlett Hall Extens 5, Boston, MA 02114 USA. EM npitteloud@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [R01-HD-15788, R01 HD015788, U54 HD028138, U54 HD029164]; NIDDK NIH HHS [DK-03892] NR 39 TC 95 Z9 103 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2005 VL 90 IS 3 BP 1317 EP 1322 DI 10.1210/jc.2004-1361 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904UQ UT WOS:000227523600007 PM 15613419 ER PT J AU Miller, KK Grieco, KA Klibanski, A AF Miller, KK Grieco, KA Klibanski, A TI Testosterone administration in women with anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POSTMENOPAUSAL WOMEN; EATING DISORDERS; PSYCHIATRIC COMORBIDITY; BODY-COMPOSITION; SPATIAL ABILITY; BULIMIA-NERVOSA; SEXUAL FUNCTION; BONE-DENSITY; YOUNG-WOMEN; DEPRESSION AB Anorexia nervosa ( AN) is complicated by severe bone loss, cognitive function deficits, and a high prevalence of major depression. We hypothesized that bone formation would increase and depressive symptoms and spatial cognition would improve with short-term physiological testosterone administration. We randomized 33 women with AN and relative testosterone deficiency to transdermal testosterone (Intrinsa, Procter and Gamble Pharmaceuticals, Cincinnati, OH), 150 mu g, 300 mu g, or placebo, for 3 wk. At baseline, free testosterone correlated with L4 bone density ( r = 0.51, P< 0.001), body mass index ( r = 0.39, P = 0.02), depressive symptoms ( r = - 0.44, P = 0.02), and spatial cognition ( r = 0.45, P = 0.04). C-terminal propeptide of type 1 collagen levels were higher during testosterone administration than placebo ( P = 0.03). The change in propeptide of type 1 collagen correlated with change in free testosterone over 3 wk ( r = 0.50, P = 0.02). Osteocalcin and bone- specific alkaline phosphatase did not change. Depressed patients receiving testosterone improved from severely depressed to moderately depressed; the placebo group was unchanged ( P = 0.02). Spatial cognition improved in the testosterone group, compared with placebo ( P = 0.0015). Therefore, short-term low-dose testosterone may improve depressive symptoms and spatial cognition in women with AN. Low-dose testosterone may also prevent decreased bone formation in AN, but because testosterone did not affect all markers of bone formation studied, further data are needed. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU NCRR NIH HHS [M01-RR01066-27, M01-RR01066-27S1]; NIDDK NIH HHS [R01-DK52625, R03-DK59297] NR 47 TC 48 Z9 49 U1 2 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2005 VL 90 IS 3 BP 1428 EP 1433 DI 10.1210/jc.2004-1181 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904UQ UT WOS:000227523600024 PM 15613421 ER PT J AU Page, ST Amory, JK Bowman, FD Anawalt, BD Matsumoto, AM Bremner, WJ Tenover, JL AF Page, ST Amory, JK Bowman, FD Anawalt, BD Matsumoto, AM Bremner, WJ Tenover, JL TI Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; HEALTHY-YOUNG MEN; MIDDLE-AGED MEN; MUSCLE STRENGTH; ADIPONECTIN LEVELS; HYPOGONADAL MEN; TRANSDERMAL TESTOSTERONE; INSULIN SENSITIVITY; REPLACEMENT THERAPY AB Testosterone ( T) therapy in older men with low serum T levels increases lean body mass and decreases fat mass. These changes might improve physical performance and strength; however, it has not been established whether T therapy improves functional outcome in older men. Moreover, concerns exist about the impact of T therapy on the prostate in older men. The administration of finasteride ( F), which partially blocks the conversion of T to the more potent androgen, dihydrotestosterone, attenuates the impact of T replacement on prostate size and prostate-specific antigen. We hypothesized that T replacement in older, hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance, strength, and body composition. Seventy men with low serum T (< 350 ng/dl), age 65 yr and older, were randomly assigned to receive one of three regimens for 36 months: 1) T enanthate, 200 mg im every 2 wk, with placebo pills daily (T-only); 2) T enanthate, 200 mg every 2 wk, with 5 mg F daily ( T + F); or 3) placebo injections and pills ( placebo). We obtained serial measurements of timed physical performance, grip strength, lower extremity strength, body composition ( by dual-energy x-ray absorptiometry), fasting cholesterol profiles, and hormones. Fifty men completed the 36-month protocol. After 36 months, T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [ 4.3 +/- 1.6% ( mean +/- SEM, T-only) and 3.8 +/- 1.0% ( T + F) vs. - 5.6 +/- 1.9% for placebo ( P < 0.002 for both T and T +F vs. placebo)] and increased handgrip strength compared with baseline and placebo ( P < 0.05). T therapy increased lean body mass [ 3.77 +/- 0.55 kg ( T-only) and 3.64 +/- 0.56 kg ( T + F) vs. - 0.21 +/- 0.55 kg for placebo ( P < 0.0001)], decreased fat mass, and significantly decreased total cholesterol, low-density lipoprotein, and leptin, without affecting high-density lipoprotein, adiponectin, or fasting insulin levels. These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months, when administered alone or when combined with F, and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men. C1 Emory Univ, Sch Med, Dept Med, Atlanta, GA 30329 USA. Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. RP Tenover, JL (reprint author), Wesley Woods Hlth Ctr, 1841 Clifton Rd NE, Atlanta, GA 30329 USA. EM page@u.washington.edu FU NHLBI NIH HHS [HL007028]; NIA NIH HHS [AG10975, K23 AG027238, K23 AG027238-01A1] NR 47 TC 289 Z9 302 U1 6 U2 17 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2005 VL 90 IS 3 BP 1502 EP 1510 DI 10.1210/jc.2004-1933 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904UQ UT WOS:000227523600036 PM 15572415 ER PT J AU Giannopoulou, I Ploutz-Synder, LL Carhart, R Weinstock, RS Fernhall, B Goulopoulou, S Kanaley, JA AF Giannopoulou, I Ploutz-Synder, LL Carhart, R Weinstock, RS Fernhall, B Goulopoulou, S Kanaley, JA TI Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE; ADIPOSE-TISSUE; ABDOMINAL FAT; WEIGHT-LOSS; PREMENOPAUSAL WOMEN; CONTROLLED-TRIAL; MELLITUS; DIET; SENSITIVITY; GLUCOSE AB This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise ( D + E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women ( body mass index, 34.6 +/- 1.9 kg/m(2)) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone ( EX), and D + E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution ( magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured preand postintervention. Body weight ( similar to 4.5 kg) and percent body fat ( similar to 5%) were decreased ( P < 0.05) with the D and D + E intervention, whereas only percent body fat ( similar to 2.3%) decreased with EX. Total abdominal fat and sc adipose tissue ( SAT) were reduced with the D and D + E interventions ( P< 0.05), whereas visceral adipose tissue ( VAT) decreased with the D + E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT ( P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels ( P < 0.05). In conclusion, modest weight loss, through either D or D + E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes. C1 Syracuse Univ, Dept Exercise Sci, Syracuse, NY 13244 USA. SUNY Upstate Med Univ, Dept Cardiol, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY 13210 USA. Vet Affairs Med Ctr, Syracuse, NY 13210 USA. RP Kanaley, JA (reprint author), Syracuse Univ, Dept Exercise Sci, 820 Comstock Ave,Room 201, Syracuse, NY 13244 USA. EM jakanale@syr.edu NR 41 TC 69 Z9 70 U1 5 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2005 VL 90 IS 3 BP 1511 EP 1518 DI 10.1210/jc.2004-1782 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904UQ UT WOS:000227523600037 PM 15598677 ER PT J AU Duda, DG Jain, RK AF Duda, DG Jain, RK TI Pleiotropy of tissue-specific growth factors: from neurons to vessels via the bone marrow SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID HEMATOPOIETIC STEM-CELLS; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; CANCER; TRANSPLANTATION; RECRUITMENT; MODEL; VEGF AB Recent evidence has demonstrated that endothelial-specific growth factors affect the development of apparently unrelated organs and cells. Expanding this evidence further, new findings in this issue of the JCI show that neurotrophic factors can affect neovascularization (see the related article beginning on page 653). Neurotrophic factors achieve proangiogenic effects not only by directly affecting endothelial cells, but also by recruiting hematopoietic precursors. Further understanding of the biology of angiogenic factors, as well as of the function of hematopoietic cells in tissue neovascularization, will lead to improved therapeutic strategies for the treatment of diseases ranging from ischemia to cancer. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 25 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2005 VL 115 IS 3 BP 596 EP 598 DI 10.1172/JCI200524511 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 902YN UT WOS:000227392700022 PM 15765145 ER PT J AU Morton, GJ Blevins, JE Williams, DL Niswender, KD Gelling, RW Rhodes, CJ Baskin, DG Schwartz, MW AF Morton, GJ Blevins, JE Williams, DL Niswender, KD Gelling, RW Rhodes, CJ Baskin, DG Schwartz, MW TI Leptin action in the forebrain regulates the hindbrain response to satiety signals SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROOPIOMELANOCORTIN MESSENGER-RNA; DECREASES FOOD-INTAKE; CAUDAL BRAIN-STEM; MELANOCYTE-STIMULATING HORMONE; LATERAL HYPOTHALAMIC AREA; CENTRAL-NERVOUS-SYSTEM; REDUCING MEAL SIZE; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; ARCUATE NUCLEUS AB The capacity to adjust energy intake in response to changing energy requirements is a defining feature of energy homeostasis. Despite the identification of leptin as a key mediator of this process, the mechanism whereby changes of body adiposity are coupled to adaptive, short-term adjustments of energy intake remains poorly understood. To investigate the physiological role of leptin in the control of meal size and the response to satiety signals, and to identify brain areas mediating this effect, we studied Koletsky (fa(k)/fa(k)) rats, which develop severe obesity due to the genetic absence of leptin receptors. Our finding of markedly increased meal size and reduced satiety in response to the gut peptide cholecystokinin (CCK) in these leptin receptor-deficient animals suggests a critical role for leptin signaling in the response to endogenous signals that promote meal termination. To determine if the hypothalamic arcuate nucleus (ARC) (a key forebrain site of leptin action) mediates this leptin effect, we used adenoviral gene therapy to express either functional leptin receptors or a reporter gene in the area of the ARC of fa(k)/fa(k) rats. Restoration of leptin signaling to this brain area normalized the effect of CCK on the activation of neurons in the nucleus of the solitary tract and area postrema, key hindbrain areas for processing satiety-related inputs. This intervention also reduced meal size and enhanced CCK-induced satiety in fa(k)/fa(k) rats. These findings demonstrate that forebrain signaling by leptin, a long-term regulator of body adiposity, limits food intake on a meal-to-meal basis by regulating the hindbrain response to short-acting satiety signals. C1 Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Pacific NW Res Inst, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98104 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, 325 9Th Ave,Box 359675, Seattle, WA 98104 USA. EM mschwart@u.washington.edu RI Schwartz, Michael/H-9950-2012; Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIDDK NIH HHS [DK52989, DK12829, DK68340, R01 DK052989]; NINDS NIH HHS [NS32273, R01 NS032273] NR 61 TC 145 Z9 150 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2005 VL 115 IS 3 BP 703 EP 710 DI 10.1172/JCI200522081 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 902YN UT WOS:000227392700034 PM 15711637 ER PT J AU Taniguchi, CM Ueki, K Kahn, CR AF Taniguchi, CM Ueki, K Kahn, CR TI Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FREE FATTY-ACIDS; INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; RNA INTERFERENCE; GLUCOSE-HOMEOSTASIS; DIABETES-MELLITUS; MAMMALIAN-CELLS; GENE-EXPRESSION; CRE RECOMBINASE; TRANSGENIC MICE AB Hepatic insulin resistance is a critical component in the development of type 2 diabetes mellitus. In many cases, insulin resistance in liver is associated with reduced expression of both major insulin receptor substrate (IRS) proteins, IRS-1 and IRS-2. To investigate the specific functions of IRS-1 and IRS-2 in regulating liver function in vivo, we developed an adenovirus-mediated RNA interference technique in which short hairpin RNAs (shRNAs) are used to knock down IRS-1, IRS-2, or both, by 70-80% in livers of WT mice. The knockdown of IRS-1 resulted in an upregulation of the gluconeogenic enzymes glucose-6 phosphatase and phosphoenolpyruvate carboxykinase, as well as a marked increase in hepatic nuclear factor-4 alpha. Decreased IRS-1 was also associated with a decrease in glucokinase expression and a trend toward increased blood glucose, whereas knockdown of IRS-2 resulted in the upregulation of lipogenic enzymes SREBP-1c and fatty acid synthase, as well. as increased hepatic lipid accumulation. The concomitant injection of IRS-1 and IRS-2 adenoviral shRNAs resulted in systemic insulin resistance, glucose intolerance, and hepatic steatosis,. The alterations in the dual-knockdown mice were associated with defective Akt activation and Foxo1 phosphorylation. Taken together, our results demonstrate that hepatic IRS-1 and IRS-2 have complementary roles in the control of hepatic metabolism, with IRS-1 more closely linked to glucose homeostasis and IRS-2 more closely linked to lipid metabolism. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo, Japan. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK33201, DK34834, DK55545, R01 DK033201, R01 DK055545] NR 58 TC 183 Z9 196 U1 4 U2 20 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2005 VL 115 IS 3 BP 718 EP 727 DI 10.1172/JCI200523187 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 902YN UT WOS:000227392700036 PM 15711641 ER PT J AU Michaud, S Menard, S Arbeit, RD AF Michaud, S Menard, S Arbeit, RD TI Role of real-time molecular typing in the surveillance of Campylobacter enteritis and comparison of pulsed-field gel electrophoresis profiles from chicken and human isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID JEJUNI; GENOTYPES; INFECTIONS AB The goal of the present study was to assess the contribution of real-time molecular typing, used alone or with clinical surveillance, to the prompt identification of clusters of Campylobacter enteritis. Potential poultry sources were sought by comparing the pulsed-field gel electrophoresis genotypes of human and fresh whole retail chicken isolates collected during the same study period. Among 183 human isolates, 82 (45%) had unique genotypes, 72 (39%) represented 26 clusters of 2 to 7 isolates each, and 29 (16%) represented three clusters of 8 to 11 isolates each. Molecular typing was useful for the confirmation of outbreaks suspected on the basis of epidemiological surveillance, but for most small clusters, no epidemiological link could be established. Thus, the added value of real-time molecular typing is questionable, since the numerous small clusters identified were of unclear public health significance. Among 177 chickens, 41 (23%) yielded campylobacter isolates; of these, 19 (46%) had genotypes similar to those of 41 (22%) human isolates. However, a temporal association was demonstrated in only a minority of cases, and most genotypes were present only in a single species, suggesting that sources other than chickens are important in human campylobacteriosis. Further investigation with samples from water and other possible environmental sources is needed to define the most efficient strategy for the application of molecular typing and identification of the source(s) of sporadic cases of campylobacteriosis. C1 Univ Sherbrooke, Fac Med, Dept Microbiol & Infect Dis, Sherbrooke, PQ J1H 5N4, Canada. Regie Reg Sante & Serv Sociaux Estrie, Direct Sante Publ, Sherbrooke, PQ, Canada. Boston Univ, Sch Med, VA Boston Healthcare Syst, Infect Dis Sect, Boston, MA 02215 USA. RP Michaud, S (reprint author), Univ Sherbrooke, Fac Med, Dept Microbiol & Infect Dis, 3001,12E Ave N, Sherbrooke, PQ J1H 5N4, Canada. EM Sophie.Michaud@USherbrooke.ca NR 15 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2005 VL 43 IS 3 BP 1105 EP 1111 DI 10.1128/JCM.43.3.1105-1111.2005 PG 7 WC Microbiology SC Microbiology GA 905AD UT WOS:000227538900016 PM 15750069 ER PT J AU Kroenke, CH Chen, WY Rosner, B Holmes, MD AF Kroenke, CH Chen, WY Rosner, B Holmes, MD TI Weight, weight gain, and survival after breast cancer diagnosis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BODY-MASS INDEX; RECEIVING ADJUVANT CHEMOTHERAPY; DISEASE-FREE SURVIVAL; POSTMENOPAUSAL WOMEN; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; YOUNG-WOMEN; OBESITY; STAGE; PROGNOSIS AB Purpose To determine whether weight prior to diagnosis and weight gain after diagnosis are predictive of breast cancer survival. Methods Patients included 5,204 Nurses' Health Study participants diagnosed with incident, invasive, nonmetastatic breast cancer between 1976 and 2000,- 860 total deaths, 533 breast cancer deaths, and 681 recurrences (defined as secondary lung, brain, bone, or liver cancer, and death from breast cancer) accrued to 2002. We computed the change in body mass index (BMI) from before to the first BMI reported ! 12 months after the date of diagnosis. Cox proportional hazards models were used to evaluate associations of categories of BMI before diagnosis and of BMI change with time to event. We stratified by smoking, menopausal status, and breast cancer-related variables. Results In multivariate-adjusted analyses, weight before diagnosis was positively associated with breast cancer recurrence and death, but this was apparent only in never smokers. Similarly, among never-smoking women, those who gained between 0.5 and 2.0 kg/m(2) (median gain, 6.0 lb; relative risk [RR], 1.35; 95% Cl, 0.93 to 1.95) or more than 2.0 kg/m(2) (median gain, 17.0 lb; RR, 1.64; 95% Cl, 1.07 to 2.51) after diagnosis had an elevated risk of breast cancer death during follow-up (median, 9 years), compared with women who maintained their weight (test for linear trend, P = .03). Associations with weight were stronger in premenopausal than in postmenopausal women. Similar findings were noted for breast cancer recurrence and all-cause mortality. Conclusion Weight and weight gain were related to higher rates of breast cancer recurrence and mortality, but associations were most apparent in never-smoking women. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kroenke, CH (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM candyce.kroenke@channing.harvard.edu FU NCI NIH HHS [CA87969]; NIA NIH HHS [AG/CA14742] NR 57 TC 291 Z9 295 U1 2 U2 21 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 MAR 1 PY 2005 VL 23 IS 7 BP 1370 EP 1378 DI 10.1200/JCO.2005.01.079 PG 9 WC Oncology SC Oncology GA 902PB UT WOS:000227367900008 PM 15684320 ER PT J AU Colleoni, M Zahrieh, D Gelber, RD Holmberg, SB Mattsson, JE Rudenstam, CM Lindtner, J Erzen, D Snyder, R Collins, J Fey, MF Thurlimann, B Crivellari, D Murray, E Mendiola, C Pagani, O Castiglione-Gertsch, M Coates, AS Price, K Goldhirsch, A AF Colleoni, M Zahrieh, D Gelber, RD Holmberg, SB Mattsson, JE Rudenstam, CM Lindtner, J Erzen, D Snyder, R Collins, J Fey, MF Thurlimann, B Crivellari, D Murray, E Mendiola, C Pagani, O Castiglione-Gertsch, M Coates, AS Price, K Goldhirsch, A TI Site of primary tumor has a prognostic role in operable breast cancer: The International Breast Cancer Study Group experience SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol ID ADJUVANT CHEMOTHERAPY; POSTOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIAL; PREMENOPAUSAL WOMEN; SURVIVAL; RISK; COMBINATION; DISSECTION; METASTASES; TAMOXIFEN AB Purpose Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease. Patients and Methods Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800;, 81%). Median follow-up was 11 years. Results A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival QFS; 10-year DES, 46% v 48%; HR, 1.10; 95% Cl, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% Cl, 1.13 to 1.32 for DFS; and HR, 1.24; 95% Cl, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DES was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% Cl, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% Cl, 1.17 to 1.67,- P = .0003 for OS). Conclusion Tumor site has a significant prognostic utility, especially for axillary lymph node-negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors. (C) 2005 by American Society of Clinical Oncology. C1 European Inst Oncol, Div Med Oncol, I-20141 Milan, Italy. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. SU Moelndals Hosp, Dept Surg, Molndal, Sweden. Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. Inst Oncol, Ljubljana, Slovenia. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Canc Council Australia, Sydney, NSW, Australia. Univ Bern, Inselspital, Inst Med Oncol, CH-3010 Bern, Switzerland. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Kantonsspital, St Gallen, Switzerland. Oncol Inst So Switzerland, Lugano, Switzerland. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Univ Cape Town, ZA-7925 Cape Town, South Africa. Madrid Breast Canc Grp, Madrid, Spain. RP Colleoni, M (reprint author), European Inst Oncol, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM marco.colleoni@ieo.it NR 27 TC 36 Z9 38 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2005 VL 23 IS 7 BP 1390 EP 1400 DI 10.1200/JCO.2005.06.052 PG 11 WC Oncology SC Oncology GA 902PB UT WOS:000227367900010 PM 15735115 ER PT J AU Galsky, MD Small, EJ Oh, WK Chen, I Smith, DC Colevas, AD Martone, L Curley, T DeLaCruz, A Scher, HI Kelly, WK AF Galsky, MD Small, EJ Oh, WK Chen, I Smith, DC Colevas, AD Martone, L Curley, T DeLaCruz, A Scher, HI Kelly, WK TI Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID MICROTUBULE-STABILIZING AGENTS; MITOXANTRONE PLUS PREDNISONE; ANTITUMOR EFFICACY; CLINICAL-TRIALS; CELL-LINES; DOCETAXEL; HYDROCORTISONE; GUIDELINES; TAXOL; MEN AB Purpose To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer. Patients and Methods Patients were randomly assigned to receive ixabepilone (35 mg/m(2)) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5. Results Between December 2001 and October 2003, 92 patients were enrolled and randomly assigned to treatment with ixabepilone alone (45 patients) or in combination with EMP (47 patients). Grades 3 and 4 toxicities experienced by more than 5% of patients included neutropenia (22%), fatigue (9%), and neuropathy (13%) on the ixabepilone arm, and neutropenia (29%), febrile neutropenia (9%), fatigue (9%), neuropathy (7%), and thrombosis (6%) on the ixabepilone + EMP arm. Post-treatment declines in prostate-specific antigen of greater than or equal to 50% were achieved in 21 of 44 patients (48%; 95% Cl, 33% to 64%) on the ixabepilone arm, and 31 of 45 patients (69%, 95% Cl, 55% to 82%) on the ixabepilone + EMP arm. In patients with measurable disease, partial responses were observed in eight of 25 patients (32%; 95% Cl, 14% to 50%) on the ixabepilone arm, and 11 of 23 (48%; 95% Cl, 27% to 68%) on the ixabepilone + EMP arm. Time to prostate-specific antigen progression was 4.4 months (95% Cl, 3.1 to 6.9 months) on the ixabepilone-alone arm and 5.2 months (95% Cl, 4.5 to 6.8 months) on the combination arm. Conclusion Ixabepilone, with or without estramustine phosphate, is well tolerated and has antitumor activity in patients with castrate metastatic prostate cancer. C1 Mem Sloan Kettering Canc Ctr, Dept Nursing, Dept Med, Div Solid Tumor Oncol,Genitourinary Oncol Serv, New York, NY 10021 USA. Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Med, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Partners Canc Care, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Natl Canc Inst, Bethesda, MD USA. RP Galsky, MD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Nursing, Dept Med, Div Solid Tumor Oncol,Genitourinary Oncol Serv, 1275 York Ave, New York, NY 10021 USA. EM galskym@mskcc.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [CM17105] NR 30 TC 137 Z9 140 U1 1 U2 2 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 MAR 1 PY 2005 VL 23 IS 7 BP 1439 EP 1446 DI 10.1200/JCO.2005.09.042 PG 8 WC Oncology SC Oncology GA 902PB UT WOS:000227367900015 PM 15735119 ER PT J AU Nguyen, PL Chakravarti, A Finkelstein, DM Hochberg, FH Batchelor, TT Loeffler, JS AF Nguyen, PL Chakravarti, A Finkelstein, DM Hochberg, FH Batchelor, TT Loeffler, JS TI Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; DEFERRED RADIOTHERAPY; SURVIVAL; THERAPY; CHEMOTHERAPY AB Purpose This study evaluates the efficacy and toxicity of whole-brain radiation therapy (WBRT) as salvage therapy for immunocompetent patients who failed initial high-dose methotrexate for primary CNS lymphoma (PCNSL). Patients and Methods The study cohort included 27 consecutive patients who failed initial high-dose methotrexate and then received salvage WBRT (median dose, 36 Gy). Actuarial survival was measured from the initiation of radiotherapy. Results Ten patients (37%) achieved a complete radiographic response (CR), and 10 patients (37%) a partial response to WBRT, for a 74% overall radiographic response rate. At the time of maximal response, Karnofsky performance status improved in 12 (44%) of 27 patients and at least stabilized in 67%. Median estimated survival from initiation of WBRT was 10.9 months (range, 0.3 to 63.7 months). The univariate predictor of longer survival was age less than 60 years at the time of WBRT (P = .028). Among patients who survived 4 months, achievement of a CR to WBRT by 4 months (P = .002) predicted longer survival. Late treatment-associated neurotoxicity was diagnosed in four patients (15%) and was significantly associated with total radiation doses greater than 36 Gy (P = .04). No patient treated with daily fractions less than 1.8 Gy developed late neurotoxicity. Conclusion For patients with PCNSL who experience treatment failure with methotrexate, WBRT provides high response rates (74%) and a median survival of 10.9 months. Age less than 60 years and response to WBRT predict post-WBRT survival. Modest rates of late neurotoxicity (15%) were seen and were associated with a total dose greater than 36 Gy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 301, Boston, MA 02114 USA. EM jloeffler@partners.org NR 19 TC 93 Z9 99 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 MAR 1 PY 2005 VL 23 IS 7 BP 1507 EP 1513 DI 10.1200/JCO.2005.01.161 PG 7 WC Oncology SC Oncology GA 902PB UT WOS:000227367900023 PM 15735126 ER PT J AU Mamon, HJ Yeap, BY Janne, PA Reblando, J Shrager, S Jaklitsch, MT Mentzer, S Lukanich, JM Sugarbaker, DJ Baldini, EH Berman, S Skarin, A Bueno, R AF Mamon, HJ Yeap, BY Janne, PA Reblando, J Shrager, S Jaklitsch, MT Mentzer, S Lukanich, JM Sugarbaker, DJ Baldini, EH Berman, S Skarin, A Bueno, R TI High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THERAPY-ONCOLOGY-GROUP; PROPHYLACTIC CRANIAL IRRADIATION; TERM-FOLLOW-UP; RANDOMIZED-TRIAL; PREOPERATIVE CHEMOTHERAPY; CARCINOMA; CISPLATIN; SURVIVAL; CHEMORADIOTHERAPY; RADIOTHERAPY AB Purpose Lung cancer is the leading cause of cancer mortality in the United States. We sought to review our experience with surgically staged IIIA (N2) non-small-cell lung cancer (NSCLC), focusing on the patterns of failure in consecutively treated patients from 1988 to 2000. Patients and Methods The records of 177 patients were reviewed. Collected data included stage, histology, use of chemotherapy and radiation, initial and subsequent sites of failure, and survival. One hundred twenty-four patients have died; follow-up time is 35 months among the remaining patients. Results The median survival from the time of surgery was 21.0 months, with a 3-year overall survival (OS) of 34%. Nodal downstaging to N0 disease correlated with OS and progression-free survival (PFS; P < .001). The most common site of recurrence was the brain. Thirty-four percent of patients recurred in the brain as their first site of failure, and 40% of patients developed brain metastases at some point in their course. In patients with nonsquamous histology and residual nodal involvement after neoadjuvant therapy, the risk of brain metastases was 53% at 3 years. Conclusion Patients treated with neoadjuvant therapy for N2-positive stage IIIA NSCLC enjoy an advantage in both OS and PFS if their lymph node status is downstaged to N-o. Because brain metastases constitute the most common site of failure in these patients, future studies focusing on prophylaxis of brain metastases may improve the outcome in patients with stage IIIA NSCLC. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Bueno, R (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM rbueno@partners.org NR 31 TC 81 Z9 86 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2005 VL 23 IS 7 BP 1530 EP 1537 DI 10.1200/JCO.2005.04.123 PG 8 WC Oncology SC Oncology GA 902PB UT WOS:000227367900026 PM 15735128 ER PT J AU Dimopoulos, MA Kyle, RA Anagnostopoulos, A Treon, SP AF Dimopoulos, MA Kyle, RA Anagnostopoulos, A Treon, SP TI Diagnosis and management of Waldenstrom's macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; ANTIBODY-MEDIATED IMMUNOTHERAPY; ANTI-CD20 MONOCLONAL-ANTIBODY; COOPERATIVE-ONCOLOGY-GROUP; MANTLE-CELL LYMPHOMA; PROGNOSTIC-FACTORS; PHASE-II; MIXED CRYOGLOBULINEMIA; RITUXIMAB THERAPY AB Purpose To review the diagnostic criteria, prognostic factors, response criteria, and treatment options of patients with Waldenstrom's macroglobulinemia (WM). Methods A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicus. Results WM should be regarded as a distinct clinicopathologic entity and confined to those patients with lymphoplasmacytoid lymphoma who have demonstrable serum immunoglobulin M monoclonal protein. Treatment decisions should rely on specific clinical and laboratory criteria. Initiation of therapy should not be based on serum monoclonal protein levels per se. The three main choices for systemic primary treatment of symptomatic patients with WM include alkylating agents (chlorambucil), nucleoside analogs (fludarabine and cladribine), and the monoclonal antibody rituximab. There are no data from prospective randomized studies to recommend the use of one first-line agent over another, although consideration of a patient's candidacy for autologous stem-cell transplantation (ASCT) should be taken into account to avoid stem cell-damaging agents. There are preliminary data to suggest that combinations of nucleoside analogs and alkylating agents with or without rituximab may improve response rates at the expense of higher toxicity. Conclusion WM is a distinct low-grade lymphoproliferative disorder. When therapy is indicated, alkylating agents, nucleoside analogs, and rituximab are reasonable choices. Several factors, including the presence of cytopenias, need for rapid disease control, candidacy for ASCT, age, and comorbidities, should be taken into consideration when choosing the most appropriate primary treatment. C1 Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. Mayo Clin, Div Hematol, Rochester, NY USA. Dana Farber Canc Inst, Dept Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dimopoulos, MA (reprint author), 227 Kifissias Ave, Athens 14561, Greece. EM mdimop@med.uoa.gr NR 112 TC 111 Z9 115 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2005 VL 23 IS 7 BP 1564 EP 1577 DI 10.1200/JCO.2005.03.144 PG 14 WC Oncology SC Oncology GA 902PB UT WOS:000227367900030 PM 15735132 ER PT J AU Aora, S Xu, C Teng, A Peterson, J Yeh, LT Gish, R Lou, D Rossi, S Lin, C AF Aora, S Xu, C Teng, A Peterson, J Yeh, LT Gish, R Lou, D Rossi, S Lin, C TI Ascending multiple-dose pharmacokinetics of viramidine, a prodrug of ribavirin, in adult subjects with compensated hepatitis C infection SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE viramidine; ribavirin; hepatitis C; pharmacokinetics ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; HUMAN-IMMUNODEFICIENCY-VIRUS; INITIAL TREATMENT; RANDOMIZED-TRIAL; TOLERANCE AB The current study was carried out to evaluate pharmacokinetic profiles of viramidine and ribavirin in patients (n = 8 per dose group) with compensated hepatitis C infection following oral dosing of viramidine (400,600, or 800 mg bid for 4 weeks). Pharmacokinetic parameters were determined on days 1 and 29 based on plasma, red blood cell, and urine concentrations of viramidine and ribavirin. The results indicate rapid absorption and conversion of viramidine to ribavirin after oral administration of viramidine, Viramidine and ribavirin exposure in plasma and RBCs generally increased from the 400- to 600-mg dose level of viramidine. However, no further increase in exposure was noted at the 800-mg dose. Long half-lives for viramidine (66-76 hours in plasma and 200-420 hours in red blood cells) and ribavirin (340-410 hours in plasma and 360-430 hours in red blood cells) were noted, A negligible amount of viramidine (1%-4% of dose) and a small amount of ribavirin (9%-14% of dose) were excreted in the urine. The renal clearance was low for both viramidine (5-8L/h) and ribavirin (4-7L/h). Significant accumulation of viramidine was noted in red blood cells (accumulation factor [R] = 5-8) but not in plasma (B = 2). Extensive accumulation of ribavirin was noted in both plasma (R = 917) and red blood cells (R = 77-129). Steady-state levels of ribavirin and viramidine in plasma and red blood cells were achieved by day 22. At steady state, there was extensive conversion of viramidine to ribavirin in both plasma and red blood cells. Both viramidine and ribavirin were preferentially distributed into red blood cells than plasma. C1 Valeant Pharmaceut Int, Res & Dev, Costa Mesa, CA 92626 USA. Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM USA. Calif Pacific Med Ctr, San Francisco, CA USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Lin, C (reprint author), Valeant Pharmaceut Int, Res & Dev, 3300 Hyland Ave, Costa Mesa, CA 92626 USA. NR 19 TC 14 Z9 15 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 2005 VL 45 IS 3 BP 275 EP 285 DI 10.1177/0031270004270152 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 896WK UT WOS:000226964700004 PM 15703363 ER PT J AU Adler, LA Spencer, TJ Milton, DR Moore, RJ Michelson, D AF Adler, LA Spencer, TJ Milton, DR Moore, RJ Michelson, D TI Long-term, open-label study of the safety and efficacy of atomoxetine in adults with attention-deficit/hyperactivity disorder: An interim analysis SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ADOLESCENTS; CHILDREN; ADHD; BUPROPION; SCALE AB Background: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neuropsychiatric disorder that affects 3% to 7% of school-age children and 4% of adults. Its pathophysiology is thought to involve the dopaminergic and noradrenergic pathways associated with attention control and impulsivity. These symptoms have largely been defined in the childhood population, but the course of the condition and expression in the adult population are not as well characterized. Method: This is an ongoing, 3-year, open-label study consisting of adults with DSM-IV ADHD who were previously enrolled in I of 2 double-blind, acute-treatment studies of atomoxetine. The results of the interim analysis reported here were derived from the study of 384 patients at 31 sites who had been studied for a period of up to 97 weeks. The primary efficacy measure was the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) total ADHD symptom score. In addition, safety, adverse events, and vital sign measurements were assessed. Results: Significant improvement was noted with atomoxetine therapy, with mean CAARS-Inv:SV total ADHD symptom scores decreasing 33.2% from 29.2 (baseline of open-label therapy) to 19.5 (endpoint of open-label therapy) (p < .001). Similar and significant decreases were noted for the secondary efficacy measures. Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects, such as increases in heart rate and blood pressure and a slight decrease in weight. Conclusion: The results of this interim analysis of an ongoing, open-label study of adults with ADHD support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. NYU, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Michelson, D (reprint author), Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM michelson@lilly.com NR 26 TC 60 Z9 61 U1 2 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 MAR PY 2005 VL 66 IS 3 BP 294 EP 299 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 907UY UT WOS:000227744700003 PM 15766294 ER PT J AU Silberbogen, AK Mori, DL Sogg, S AF Silberbogen, AK Mori, DL Sogg, S TI The structured interview for the treatment of the hepatitis C virus (SIT-HCV) SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE hepatitis C virus; interferon treatment; psychological evaluation; medical outcomes ID QUALITY-OF-LIFE; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; INITIAL TREATMENT; RANDOMIZED-TRIAL; INFECTION AB The purpose of this paper is to introduce the Structured Interview for the Treatment of the Hepatitis C Virus ( SIT-HCV). This comprehensive interview expands upon a standard psychiatric interview by including those medical, psychological, and behavioral factors that are essential to determining a patient's psychological appropriateness for interferon therapy. A detailed description of the SIT-HCV is provided, highlighting its utility in developing recommendations that positively impact patients' treatment outcomes. The advantages of the SIT-HCV will be presented, including a discussion on how this approach can ensure comprehensive assessment and facilitate research, training, and patient education. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Weight Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Silberbogen, AK (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM amy.silberbogen@med.va.gov NR 25 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD MAR PY 2005 VL 12 IS 1 BP 57 EP 69 DI 10.1007/s10880-005-0912-1 PG 13 WC Psychology, Clinical SC Psychology GA 896MV UT WOS:000226939100005 ER PT J AU Niles, BL Mori, DL Lambert, JF Wolf, EJ AF Niles, BL Mori, DL Lambert, JF Wolf, EJ TI Depression in primary care: Comorbid disorders and related problems SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE depression; primary care; comorbidity; lifestyle ID PSYCHOMETRIC PROPERTIES; PSYCHIATRIC-DISORDERS; CIGARETTE-SMOKING; MAJOR DEPRESSION; FOLLOW-UP; ANXIETY; INVENTORY; SYMPTOMS; EXERCISE; DYSFUNCTION AB Identifying and treating depression has been a major focus in primary care over the last decade. Unfortunately, treatments have not been as successful as originally hoped. The current study investigated factors that may contribute to poor outcomes in a sample of VA primary care patients. Results indicate that 15.5% of the patients in this investigation had significant symptoms of depression. The vast majority (89.6%) of these patients also had significant symptoms of at least one additional comorbid psychiatric condition. Furthermore, an association between depression and unhealthy behaviors ( smoking, not exercising) was demonstrated. Finally, sexual dysfunction and chronic pain were more frequently observed in individuals with depressive symptoms. These findings illustrate that depression is only one of many problems for most primary care patients identified with depression. A multidisciplinary team in primary care is recommended to provide a coordinated approach to the treatment of depression and its associated problems. C1 PTSD, VA Boston Healthcare Syst, Natl Ctr, Behav Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Vet Adm Providence Healthcare Syst, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Niles, BL (reprint author), PTSD, VA Boston Healthcare Syst, Natl Ctr, Behav Sci Div, 116-B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM barbara.niles@med.va.gov OI Wolf, Erika/0000-0003-2666-2435 NR 49 TC 6 Z9 6 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD MAR PY 2005 VL 12 IS 1 BP 71 EP 77 DI 10.1007/s10880-005-0914-z PG 7 WC Psychology, Clinical SC Psychology GA 896MV UT WOS:000226939100006 ER PT J AU Galande, AK Weissleder, R Tung, CH AF Galande, AK Weissleder, R Tung, CH TI An effective method of on-resin disulfide bond formation in peptides SO JOURNAL OF COMBINATORIAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; PROTEIN CONJUGATION; SULFHYDRYL-GROUPS; DRUG-DELIVERY; CYSTEINE; PROTECTION; BRIDGES; CANCER; NPYS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5410, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01-CA99385] NR 26 TC 24 Z9 25 U1 1 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-4766 J9 J COMB CHEM JI J. Comb. Chem. PD MAR-APR PY 2005 VL 7 IS 2 BP 174 EP 177 DI 10.1021/cc049839r PG 4 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 907HV UT WOS:000227708100003 PM 15762743 ER PT J AU Lembcke, A Koch, C Dohmen, PM Rutsch, WF Abbara, S Krug, LD Muehler, MR Rogalla, P AF Lembcke, A Koch, C Dohmen, PM Rutsch, WF Abbara, S Krug, LD Muehler, MR Rogalla, P TI Electrocardiographic-gated multislice computed tomography for visualization of cardiac morphology in congenitally corrected transposition of the great arteries SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE congenital heart defects; imaging; cardiac surgery; multislice computed tomography; transposition of great vessels ID ATRIOVENTRICULAR-BLOCK; HEART-DISEASE; VESSELS; ADULTS; SYSTEM; CT AB A case of congenitally corrected transposition of the great arteries in a 64-old-woman is presented. Diagnosis was missed by invasive angiocardiography. Electrocardiographic-gated multislice computed tomography not only demonstrated switching of the aortic root and pulmonary trunk but clearly identified fine morphologic details of the cardiac chambers, including the atypical coronary artery pattern. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Free Univ Berlin, Charite Univ Med, Berlin Med Sch, Dept Radiol, D-1000 Berlin, Germany. Humboldt Univ, Berlin, Germany. Harvard Univ, Sch Med, Boston, MA 02115 USA. Free Univ Berlin, Charite Univ Med, Berlin Med Sch, Dept Cardiovasc Surg, D-1000 Berlin, Germany. Free Univ Berlin, Charite Univ Med, Berlin Med Sch, Dept Cardiol Angiol Pneumol Internal Med 1, D-1000 Berlin, Germany. RP Lembcke, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White Bldg,Room 270, Boston, MA 02114 USA. EM alexander.lembcke@gmx.de NR 13 TC 5 Z9 5 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 MAR-APR PY 2005 VL 29 IS 2 BP 234 EP 237 DI 10.1097/01.rct.0000156198.02741.c0 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 911UH UT WOS:000228030400016 PM 15772544 ER PT J AU Dodds, MWJ Johnson, DA Yeh, CK AF Dodds, MWJ Johnson, DA Yeh, CK TI Health benefits of saliva: a review SO JOURNAL OF DENTISTRY LA English DT Article; Proceedings Paper CT Symposium in Honour of the Work of Professor WM Edgor CY OCT 07, 2001 CL Cumbria, ENGLAND DE saliva; aging; diabetes; hypertension ID PROLINE-RICH PROTEINS; HUMAN-PAROTID SALIVA; DEPENDENT DIABETES-MELLITUS; CARIES-FREE INDIVIDUALS; ORAL SUGAR CLEARANCE; HUMAN WHOLE SALIVA; FLOW-RATES; DENTAL-CARIES; APATITIC SURFACES; PH CHANGES AB Objective. The aim is to present a review of the literature on human saliva composition, flow rates and some of the health benefits of saliva, with emphasis on studies from our laboratory that have looked at effects of age and age-related diseases on saliva output and composition. Data. Saliva influences oral health both through its non-specific physico-chemical properties, as well as through more specific effects. The proline-rich proteins, statherin and the histatins are salivary proteins that influence calcium phosphate chemistry, initial plaque formation and candida infection. Increases or decreases in mastication may affect saliva output. Our cross-sectional studies of saliva in a large population-based study cohort (N=1130) indicate that there is an age-related decline in saliva output for unstimulated whole, stimulated parotid, unstimulated submandibular/sublingual and stimulated submandibular/sublingual saliva, as well as some compositional alterations in anti-microbial and other proteins. Some of these alterations also appear to be specific for certain age-related medical conditions, such as diabetes mellitus. Conclusions. These studies and data presented confirm the importance of saliva in maintaining a healthy oral environment; the practitioner is encouraged to consider saliva output and medical conditions that may compromise it as part of routine dental treatment planning. (c) 2004 Elsevier Ltd. All rights reserved. C1 Wm Wrigley Jr Co, Chicago, IL 60609 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. RP Dodds, MWJ (reprint author), Wm Wrigley Jr Co, 3535 S Ashland Ave, Chicago, IL 60609 USA. EM mdodds@wrigley.com FU NIDCR NIH HHS [DE 10756] NR 92 TC 215 Z9 237 U1 7 U2 61 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0300-5712 J9 J DENT JI J. Dent. PD MAR PY 2005 VL 33 IS 3 BP 223 EP 233 DI 10.1016/j.jdent.2004.10.009 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 905RN UT WOS:000227587400007 PM 15725522 ER PT J AU McNeely, MJ Boyko, EJ AF McNeely, MJ Boyko, EJ TI Diabetes-related comorbidities in Asian Americans - Results of a National Health Survey SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE diabetes in minorities; National Health Surveys; complications; hypertension; hypercholesterolemia ID LOWER-EXTREMITY AMPUTATION; BLOOD-GLUCOSE; POPULATION; DISEASE; RISK; NEPHROPATHY; PREVALENCE; NEUROPATHY; VETERANS; HEIGHT AB Objective: The aim of this study was to compare the prevalence of diabetes-related comorbidities in Asian Americans to the prevalence in other racial and ethnic groups in the United States using data from the 2001 Behavioral Risk Factor Surveillance System (BRFSS). Methods: The BRFSS is a population-based telephone survey of the health status and health behaviors of 212,510 Americans aged 18 years in all 50 states, Guam, Puerto Rico, and the U.S. Virgin Islands. In 2001, participants included 196 Asian Americans, 1138 African Americans, 1276 Hispanics, 294 Native Americans, 71 Pacific Islanders, and 7799 non-Hispanic Whites with a self-reported physician diagnosis of diabetes. Comorbidity was determined by self-report. Odds ratios (OR) were adjusted for age, sex, body mass index (BMI) or height and weight, duration of diabetes, smoking, and health-insurance status. Results: The adjusted prevalences of hypercholesterolemia and retinopathy were similar across groups. Relative to Asian Americans, only African Americans were more likely to report hypertension [adjusted OR = 2.1, 95% confidence interval (CI) = 1.0-4.2, P < .05]. Higher odds of current or past foot ulceration was observed for Hispanics (adjusted OR = 2.8, 95% CI = 1.2-6.9), Native Americans (adjusted OR = 4.2, 95% CI = 1.4-12.8), and Pacific Islanders (adjusted OR = 7.4, 95% CI = 1.3-41.2) compared with Asian Americans. Conclusions: Among Americans with diabetes, Asian Americans have a prevalence of hypertension, hypercholesterolemia, retinopathy, and foot ulceration that is similar to that in Whites. Asian Americans had a significantly lower prevalence of hypertension than African Americans did and a lower prevalence of foot ulceration than Hispanics, Native Americans, and Pacific Islanders did. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Washington, Div Gen Internal Med, Dept Med, Seattle, WA 98105 USA. Vet Affairs Epidemiol Res & Informat Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP McNeely, MJ (reprint author), Univ Washington, Div Gen Internal Med, Dept Med, Campus Box 354981,Suite 230,4311 11th Ave NE, Seattle, WA 98105 USA. EM mcneely@u.washington.edu NR 17 TC 16 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR-APR PY 2005 VL 19 IS 2 BP 101 EP 106 DI 10.1016/j.jdiacomp.2004.08.003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 908NZ UT WOS:000227795000007 PM 15745840 ER PT J AU Fan, VS Burman, M McDonell, MB Fihn, SD AF Fan, VS Burman, M McDonell, MB Fihn, SD TI Continuity of care and other determinants of patient satisfaction with primary care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient satisfaction; health services research; quality of care; questionnaire design; linear models ID QUALITY-OF-LIFE; MEDICAL-CARE; GENERAL-PRACTICE; HEALTH-STATUS; OLDER PATIENTS; META-ANALYSIS; PHYSICIANS; SERVICES; OUTCOMES; HOSPITALIZATION AB OBJECTIVE: The patient-clinician relationship is a central feature of primary care, and recent developments in the delivery of health care have tended to limit continuity of care. The objective of this study was to evaluate the extent to which continuity of care and other factors are related to patient satisfaction. DESIGN: Cross-sectional, mailed questionnaire study. SETTING: Primary care clinics at 7 Veterans Affairs medical centers. PATIENTS/PARTICIPANTS: Patients (N=21,689) participating in the Ambulatory Care Quality Improvement Project who returned the baseline Seattle Outpatient Satisfaction Questionnaire (SOSQ). MEASUREMENTS AND MAIN RESULTS: We evaluated the association between self-reported continuity and satisfaction, after adjusting for characteristics of patients, clinics, and providers. The humanistic scale of the SOSQ measures patient satisfaction with communication skills and humanistic qualities of providers, whereas the organizational scale measures satisfaction with delivery of health care services. The mean adjusted humanistic score for patients who reported always seeing the same provider was 17.3 (95% confidence interval [CI], 15.5 to 19.1) points higher than for those who rarely saw the same provider. Similarly, the mean adjusted organizational score was 16.3 (95% CI, 14.5 to 18.1) points higher for patients who always saw the same provider compared to rarely. Demographic factors, socioeconomic status, health status, clinic site, and patient utilization of services were all associated with both the adjusted humanistic and organizational scores of the SOSQ. CONCLUSIONS: Self-reported continuity of care is strongly associated with higher patient satisfaction. This suggests that improving continuity of care may improve patient satisfaction with providers as well as with their health care organization. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Fan, VS (reprint author), 1660 S Columbian Way, Seattle, WA 98108 USA. EM vfan@u.washington.edu NR 56 TC 102 Z9 103 U1 3 U2 17 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2005 VL 20 IS 3 BP 226 EP 233 DI 10.1111/j.1525-1497.2005.40135.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 915UB UT WOS:000228335700003 PM 15836525 ER PT J AU Pearlman, RA Hsu, C Starks, H Back, AL Gordon, JR Bharucha, AJ Koenig, BA Battin, MP AF Pearlman, RA Hsu, C Starks, H Back, AL Gordon, JR Bharucha, AJ Koenig, BA Battin, MP TI Motivations for physician-assisted suicide - Patient and family voices SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-05, 2001 CL SAN DIEGO, CA SP Soc Gen Internal Med DE physician-assisted suicide; euthanasia; decision making; end-of-life issues; qualitative research ID TERMINALLY-ILL PATIENTS; EUTHANASIA; ATTITUDES; REQUESTS; OREGON; DEATH; HOPELESSNESS; ONCOLOGISTS; EXPERIENCES; CARE AB OBJECTIVE: To obtain detailed narrative accounts of patients' motivations for pursuing physician-assisted suicide (PAS). DESIGN: Longitudinal case studies. PARTICIPANTS: Sixty individuals discussed 35 cases. Participants were recruited through advocacy organizations that counsel individuals interested in PAS, as well as hospices and grief counselors. SETTING: Participants' homes. MEASUREMENTS AND RESULTS: We conducted a content analysis of 159 semistructured interviews with patients and their family members, and family members of deceased patients, to characterize the issues associated with pursuit of PAS. Most patients deliberated about PAS over considerable lengths of time with repeated assessments of the benefits and burdens of their current experience. Most patients were motivated to engage in PAS due to illness-related experiences (e.g., fatigue, functional losses), a loss of their sense of self, and fears about the future. None of the patients were acutely depressed when planning PAS. CONCLUSIONS: Patients in this study engaged in PAS after a deliberative and thoughtful process. These motivating issues point to the importance of a broad approach in responding to a patient's request for PAS. The factors that motivate PAS can serve as an outline of issues to explore with patients about the far-reaching effects of illness, including the quality of the dying experience. The factors also identify challenges for quality palliative care: assessing patients holistically, conducting repeated assessments of patients' concerns over time, and tailoring care accordingly. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Natl Ctr Eth Hlth Care VHA, Washington, DC USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med Hist, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Stanford Univ, Ctr Biomed Eth, Stanford, CA 94305 USA. Univ Utah, Dept Philosophy, Salt Lake City, UT USA. RP Pearlman, RA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way S-182-GRECC, Seattle, WA 98108 USA. EM Robert.Pearlman@med.va.gov NR 34 TC 32 Z9 32 U1 5 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2005 VL 20 IS 3 BP 234 EP 239 DI 10.1111/j.1525-1497.2005.40225.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 915UB UT WOS:000228335700004 PM 15836526 ER PT J AU Beach, MC Saha, S AF Beach, MC Saha, S TI Free to be you and me? Balancing professionalism, culture, and self-expression SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID ATTITUDES; APPEARANCE; PHYSICIANS C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Portland VA Med Ctr, Portland, OR USA. RP Beach, MC (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 8 TC 3 Z9 3 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2005 VL 20 IS 3 BP 312 EP 313 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 915UB UT WOS:000228335700016 PM 15836538 ER PT J AU Wilhelmi, BJ Kang, RH Wages, DJ Lee, WPA May, JW AF Wilhelmi, BJ Kang, RH Wages, DJ Lee, WPA May, JW TI Optimizing independent finger flexion with zone V flexor repairs using the Massachusetts General Hospital flexor tenorrhaphy and early protected active motion SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE flexor tendon; MGH repair; hand therapy; early protected active motion; optimizing tendon excursion; independent finger flexion; zone V flexor repair ID SPAGHETTI WRIST; TENDON REPAIR; BIOMECHANICAL ANALYSIS; MECHANICAL ANALYSIS; LACERATIONS; MANAGEMENT; INJURIES AB Purpose: Independent FDS action has been cited to be problematic with repair of multiple tendons in zone V owing to adhesion formation between the flexor digitorum superficialis (FDS) and the flexor digitorum profundus (FDP) tendons. Of the several described flexor repair techniques the ideal tendon repair should be strong enough to allow for early active motion to minimize adhesion formation and maximize tendon healing. Biomechanical studies have proven the Massachusetts General Hospital (MGH) repair to be strong enough to allow for early active motion. The purpose of this study was to examine the use of the MGH technique for zone V flexor tendon injuries to allow for early protected active motion to achieve independent finger flexion through better differential gliding of the tendons. Methods: We performed a retrospective review 168 zone V finger flexor tendon repairs for 29 patients performed consecutively over 4 years when early active motion was not contraindicated. The same early protected active motion protocol was used for all of these patients. We reviewed total active motion, independent flexion, rupture, and need for tenolysis. These injuries involved 103 FDS and 65 FDP tendons to 103 fingers. The median follow-up period was 24 weeks. Of these 29 patients 19 were men and 10 were women. The average patient age was 28 years. Results: The total active motion for these zone V repairs was 236 degrees +/- 5 degrees Overall 97 of 103 digits attained good to excellent function and 88 of 103 developed some differential glide. One of these patients required a tenolysis. Three repairs ruptured in 1 patient owing to suture breakage that was associated with noncompliance with the dorsal extension block splint. Conclusions: Our retrospective review of 168 consecutive flexor tendon repairs showed that the MGH technique allowed for early protected active motion, which provided good to excellent functional outcomes with 88 of 103 developing independent finger flexion at an acceptably low complication risk. Copyright (c) 2005 by the American Society for Surgery of the Hand. C1 So Illinois Univ, Sch Med, Plast Surg Inst, Springfield, IL 62794 USA. Mercy Hosp, Pittsburgh, PA 15219 USA. Univ Pittsburgh, Pittsburgh, PA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Newton Wellesley Hosp, Boston, MA USA. RP Wilhelmi, BJ (reprint author), So Illinois Univ, Sch Med, Plast Surg Inst, 747 N Rutledge,POB 19653, Springfield, IL 62794 USA. NR 29 TC 5 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2005 VL 30A IS 2 BP 230 EP 236 DI 10.1016/j.jhsa.2004.07.009 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 908XY UT WOS:000227824700003 PM 15781344 ER PT J AU Kramer, JR Giordano, TP Souchek, J El-Serag, HB AF Kramer, JR Giordano, TP Souchek, J El-Serag, HB TI Hepatitis C coinfection increases the risk of fulminant hepatic failure in patients with HIV in the HAART era SO JOURNAL OF HEPATOLOGY LA English DT Article DE hepatitis C virus; HIV coinfection; fulminant hepatic failure; Veterans Affairs Medical Center; retrospective cohort study; highly active antiretroviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONTAINING ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; PROTEASE INHIBITORS; LIVER-FAILURE; HEPATOTOXICITY; NEVIRAPINE; MORTALITY; DISEASE; IMPACT AB Background/Aims: It is uncertain if patients coinfected with hepatitis C and HIV are more likely to suffer fulminant hepatic failure (FHF) when compared to patients with HIV-only. Methods: We conducted a retrospective cohort study using national administrative databases from the Department of Veterans Affairs in patients hospitalized for the first time with HIV and/or hepatitis C between 10/1991 and 9/2000. Fulminant hepatic failure was defined as occurring after the index hospitalization through 9/2001 in the absence of preexisting liver disease. We calculated incidence rates, Kaplan Meier cumulative incidence curves, and Cox proportional hazards ratios while adjusting for demographics and other potential confounders. Results: We identified 11,678 patients with HIV-only and 4761 patients with coinfection. There were 92 cases of fulminant hepatic failure yielding an incidence rate of 1.1/1000 person-years and 2.5/1000 person-years in the HIV-only and coinfected groups. The cumulative incidence of fulminant hepatic failure in the coinfected group was higher than in the HIV-only group (P < 0.0001). The risk of fulminant hepatic failure in patients with coinfection compared to HIV-only during the HAART era was several folds higher than that during the pre-HAART era. Conclusions: HAART and hepatitis C coinfection appeared to act synergistically in HIV-infected patients to increase the risk of fulminant hepatic failure, a rare but often fatal disease. (c) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Gastroenterol Sect, Dept Med, Houston, TX 77030 USA. RP Kramer, JR (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. EM jkramer@bcm.tmc.edu FU NIMH NIH HHS [K23MH67505] NR 23 TC 50 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2005 VL 42 IS 3 BP 309 EP 314 DI 10.1016/j.jhep.2004.11.017 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 905BP UT WOS:000227542900006 PM 15710213 ER PT J AU Ghosh, S Steere, AC Stollar, BD Huber, BT AF Ghosh, S Steere, AC Stollar, BD Huber, BT TI In situ diversification of the antibody repertoire in chronic Lyme arthritis synovium SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BORRELIA-BURGDORFERI LIPOPROTEINS; OUTER SURFACE LIPOPROTEINS; J-LAMBDA REPERTOIRE; FREE LIGHT-CHAINS; B-CELLS; RHEUMATOID-ARTHRITIS; VARIABLE REGION; MOLECULAR-MECHANISMS; MONOCLONAL-ANTIBODY; TREPONEMA-PALLIDUM AB Lyme arthritis is initiated by the tick-borne spirochete, Borrelia burgdorferi. In a subset of patients, symptoms do not resolve in response to standard courses of antibiotics. Chronic joint inflammation may persist despite spirochetal killing, suggesting an autoimmune etiology. The pathogenic mechanisms that sustain chronic Lyme arthritis have not been fully elucidated, although T cells are believed to play a role. The synovial lesion contains elements of a peripheral lymph node, with lymphoid aggregates, plasma cells and follicular dendritic cells. An analysis of activated cells at the site of injury could yield clues regarding the nature of the response and the identity of potential autoantigens. Using laser-capture microdissection, we have isolated plasma cells from the joint tissue of chronic Lyme arthritis patients who underwent synovectomy. Expressed Ig V regions were amplified by RT-PCR. A majority of isolated cells expressed gamma H chains, which is indicative of a class-switched response. There were a large number of nucleotide substitutions from germline, with a higher fraction of replacement mutations in the CDRs, suggesting a process of Ag-driven selection. We have recovered clonal clusters of cells containing identical junctions and V(D)J rearrangements. Sequence analysis reveals a hierarchy of shared somatic mutations between members of a given clone. Intraclonal diversity among plasma cells of close physical proximity points toward an ongoing process of diversification and affinity maturation, possibly driven by the chronic presence of an autoantigen. C1 Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Huber, BT (reprint author), Tufts Univ, Sch Med, Dept Pathol, 150 Harrison Ave, Boston, MA 02111 USA. EM brigitte.huber@tufts.edu FU NCRR NIH HHS [MO1-RR0054]; NIAMS NIH HHS [AR45386] NR 65 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2005 VL 174 IS 5 BP 2860 EP 2869 PG 10 WC Immunology SC Immunology GA 899UX UT WOS:000227172100052 PM 15728496 ER PT J AU Crowley, W AF Crowley, W TI William Crowley, MD SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Harvard Wide Reproduct Endocrine Ctr, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Reproduct Endocrine Unit, Boston, MA 02114 USA. RP Crowley, W (reprint author), Harvard Univ, Sch Med, Harvard Wide Reproduct Endocrine Ctr, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2005 VL 53 IS 2 BP 49 EP 53 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 909FU UT WOS:000227846600001 PM 15810486 ER PT J AU Mitsiades, CS Mitsiades, N Richardson, PG Anderson, KC AF Mitsiades, CS Mitsiades, N Richardson, PG Anderson, KC TI Molecular predictors of clinical response to the proteasome inhibitor bortezomib: Clinical implications for individualized patient-specific anti-cancer therapeutic algorithms. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Joint Annual Meeting of the Central-Society-for-Clinical-Research/Midwestern American-Federation-for-Medical-Research CY APR, 2005 CL Chicago, IL SP Cent Soc Clin Res, Midwestern Amer Federat Med Res C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2005 VL 53 IS 2 BP S387 EP S387 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 909FU UT WOS:000227846600090 ER PT J AU Kim, JW Simmer, JP Hart, TC Hart, PS Ramaswami, MD Bartlett, JD Hu, JCC AF Kim, JW Simmer, JP Hart, TC Hart, PS Ramaswami, MD Bartlett, JD Hu, JCC TI MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MATRIX METALLOPROTEINASE-20; MOUSE ENAMELYSIN; EXPRESSION; NOMENCLATURE; GENE; PROTEINASES; HYDROLYSIS; ACTIVATION; MATURATION; CLONING C1 Seoul Natl Univ, Coll Dent, Dept Pediat Dent, Seoul, South Korea. Seoul Natl Univ, Dent Res Inst, Seoul, South Korea. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. NIDCR, NIH, Bethesda, MD USA. Forsyth Inst, Harvard Forsyth Dept Cytokine Biol, Boston, MA USA. Forsyth Inst, Harvard Forsyth Dept Cytokine Biol, Boston, MA USA. Univ Michigan, Sch Dent, Dept Pediat Dent, Ann Arbor, MI 48109 USA. RP Hu, JCC (reprint author), Univ Michigan, Dent Res Lab, Dept Orthodont & Pediat Dent, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA. EM janhu@umich.edu RI KIM, JUNG-WOOK/G-8992-2012 FU NIDCR NIH HHS [DE11301, DE12769, DE15846, R01 DE014084] NR 37 TC 131 Z9 135 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAR PY 2005 VL 42 IS 3 BP 271 EP 275 DI 10.1136/jmg.2004.024505 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 904BO UT WOS:000227470300013 PM 15744043 ER PT J AU Jensen, RJ Ziv, OR Rizzo, JF AF Jensen, Ralph J. Ziv, Ofer R. Rizzo, Joseph F. TI Responses of rabbit retinal ganglion cells to electrical stimulation with an epiretinal electrode SO JOURNAL OF NEURAL ENGINEERING LA English DT Article AB Rational selection of electrical stimulus parameters for an electronic retinal prosthesis requires knowledge of the electrophysiological responses of retinal neurons to electrical stimuli. In this study, we examined the effects of cathodal and anodal current pulses on the extracellularly recorded responses of OFF and ON rabbit retinal ganglion cells (RGCs) in an in vitro preparation. Current pulses (1 msec duration), delivered by a 125 mu m electrode placed on the inner retinal surface within the receptive field of a RGC, produced both short-latency (<= 5 msec) and long-latency (8-60 msec) responses. The long-latency responses, but not the short-latency responses, were abolished upon application of the glutamate receptor antagonists CNQX and NBQX, thus indicating that the long-latency responses of RGCs are due to activation of presynaptic neurons in the retina. The latency of the long-latency response depended upon the polarity of the stimulus. For OFF RGCs, the average latency was 11 msec for a cathodal stimulus and 24 msec for an anodal stimulus. For ON RGCs, the average latency was 25 msec for a cathodal stimulus and 16 msec for an anodal stimulus. The threshold current also depended upon the polarity of the stimulus, at least for OFF RGCs. The average threshold current for evoking a long-latency response in OFF RGCs was 10 mu A for a cathodal stimulus and 21 mu A for an anodal stimulus. In ON RGCs, the average threshold current was 13 mu A for a cathodal stimulus and 15 mu A for an anodal stimulus. C1 [Jensen, Ralph J.; Ziv, Ofer R.; Rizzo, Joseph F.] VA Med Ctr, Ctr Innovat Visual Rehabil, Mail Stop 151E,150 South Huntington Ave, Boston, MA 02130 USA. [Ziv, Ofer R.] MIT, Elect Res Lab, 36-576,77 Massachusetts Ave, Cambridge, MA 02139 USA. [Rizzo, Joseph F.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Jensen, RJ (reprint author), VA Med Ctr, Ctr Innovat Visual Rehabil, Mail Stop 151E,150 South Huntington Ave, Boston, MA 02130 USA. EM Ralph.Jensen@med.va.gov FU Department of Veterans Affairs, Rehabilitation Research and Development Service [C-2726-C, C-3022-R] FX This work was supported by the Department of Veterans Affairs, Rehabilitation Research and Development Service (Project # C-2726-C and C-3022-R). NR 30 TC 72 Z9 72 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD MAR PY 2005 VL 2 IS 1 SI SI BP S16 EP S21 DI 10.1088/1741-2560/2/1/003 PG 6 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA V43HJ UT WOS:000209672200003 PM 15876650 ER PT J AU Yamauchi, Y Franco, LM Jackson, DJ Naber, JF Ziv, RO Rizzo, JF Kaplan, HJ Enzmann, V AF Yamauchi, Yasuyuki Franco, Luisa M. Jackson, Douglas J. Naber, John F. Ziv, R. Ofer Rizzo, Joseph F., III Kaplan, Henry J. Enzmann, Volker TI Comparison of electrically evoked cortical potential thresholds generated with subretinal or suprachoroidal placement of a microelectrode array in the rabbit SO JOURNAL OF NEURAL ENGINEERING LA English DT Article AB The aim of the study was to directly compare the threshold electrical charge density of the retina (retinal threshold) in rabbits for the generation of electrical evoked potentials (EEP) by delivering electrical stimulation with a custom-made microelectrode array (MEA) implanted into either the subretinal or suprachoroidal space. Nine eyes of seven Dutch-belted rabbits were studied. The electroretinogram (ERG), visual evoked potentials (VEP) and EEP were recorded. Electrodes for the VEP and EEP were placed on the dura mater overlying the visual cortex. The EEP was recorded following electrical stimulation of the MEA placed either subretinally beneath the visual streak of the retina or in the suprachoroidal space in the rabbit eye. An ab externo approach was used for placement of the MEA. Liquid perfluorodecaline (PFCL; 0.4 ml) was placed within the vitreous cavity to flatten the neurosensory retina on the MEA after subretinal implantation. The retinal threshold for generation of an EEP was determined for each MEA placement by three consecutive measurements consisting of 100 computer-averaged recordings. Animals were sacrificed at the conclusion of the experiment and the eyes were enucleated for histological examination. The retinal threshold to generate an EEP was 9 +/- 7 nC (0.023 +/- 0.016 mC cm(-2)) within the subretinal space and 150 +/- 122 nC (0.375 +/- 0.306 mC cm(-2)) within the suprachoroidal space. Histology showed disruption of the outer retina with subretinal but not suprachoroidal placement. The retinal threshold to elicit an EEP is significantly lower with subretinal placement of the MEA compared to suprachoroidal placement (P < 0.05). The retinal threshold charge density with a subretinal MEA is well below the published charge limit of 1 mC cm(-2), which is the level below which chronic stimulation of the retina is considered necessary to avoid tissue damage (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6). C1 [Yamauchi, Yasuyuki; Franco, Luisa M.; Kaplan, Henry J.; Enzmann, Volker] Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, 301 E Muhammad Ali Blvd, Louisville, KY 40202 USA. [Jackson, Douglas J.; Naber, John F.] Univ Louisville, Dept Elect & Comp Engn, Speed Sch Engn, Louisville, KY 40292 USA. [Ziv, R. Ofer; Rizzo, Joseph F., III] VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Yamauchi, Y (reprint author), Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, 301 E Muhammad Ali Blvd, Louisville, KY 40202 USA. EM volker.enzmann@louisville.edu FU Charles D Kelman, MD Postdoctoral Scholar Award; Boston VA Hospital [V523P-7278]; Research to Prevent Blindness, New York City, NY; Kentucky Research Challenge Trust Fund FX Supported in part by The Charles D Kelman, MD Postdoctoral Scholar Award 2003 (YY); Boston VA Hospital (V523P-7278); Research to Prevent Blindness, New York City, NY and Kentucky Research Challenge Trust Fund (HJK). NR 36 TC 45 Z9 46 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD MAR PY 2005 VL 2 IS 1 SI SI BP S48 EP S56 DI 10.1088/1741-2560/2/1/007 PG 9 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA V43HJ UT WOS:000209672200007 PM 15876654 ER PT J AU Ziv, OR Rizzo, JF Jensen, RJ AF Ziv, Ofer R. Rizzo, Joseph F., III Jensen, Ralph J. TI In vitro activation of retinal cells: estimating location of stimulated cell by using a mathematical model SO JOURNAL OF NEURAL ENGINEERING LA English DT Article AB Activation of neurons at different depths within the retina and at various eccentricities from the stimulating electrode will presumably influence the visual percepts created by a retinal prosthesis. With an electrical prosthesis, neurons will be activated in relation to the stimulating charge that impacts their cell membranes. The common model used to predict charge density is Coulomb's law, also known as the square law. We propose a modified model that can be used to predict neuronal depth that takes into account: (1) finite dimensions related to the position and size of the stimulating and return electrodes and (2) two-dimensional displacements of neurons with respect to the electrodes, two factors that are not considered in the square law model. We tested our model by using in vitro physiological threshold data that we had obtained previously for eight OFF-center brisk-transient rabbit retinal ganglion cells. For our most spatially dense threshold data (25 mu m increments up to 100 mu m from the cell body), our model estimated the depth of one RGC to be 76 +/- 76 mu m versus 87 +/- 62 mu m (median: SD) for the square law model, respectively. This difference was not statistically significant. For the seven other RGCs for which we had obtained threshold data up to 800 mu m from the cell body, the estimate of the RGC depth (using data obtained along the X axis) was 96 +/- 74 versus 20 +/- 20 mu m for the square law and our modified model, respectively. Although this difference was not statistically significant (Student t-test: p = 0.12), our model provided median values much closer to the estimated depth of these RGCs (>> 25 mu m). This more realistic estimate of cell depth predicted by our model is not unexpected in this latter data set because of the more spatially distributed threshold data points that were evaluated. Our model has theoretical advantages over the traditional square law model under certain conditions, especially when considering neurons that are horizontally displaced from the stimulating electrode. Our model would have to be tested with a larger threshold data pool to permit more conclusive statements about the relative value of our model versus the traditional square law model under special circumstances. C1 [Ziv, Ofer R.; Rizzo, Joseph F., III; Jensen, Ralph J.] VA Med Ctr, Ctr Innovat Visual Rehabil, Mail Stop 151E,150 South Huntington Ave, Boston, MA 02130 USA. [Ziv, Ofer R.] MIT, Elect Res Lab, 36-576,77 Massachusetts Ave, Cambridge, MA 02139 USA. [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Ziv, OR (reprint author), VA Med Ctr, Ctr Innovat Visual Rehabil, Mail Stop 151E,150 South Huntington Ave, Boston, MA 02130 USA. EM Robert.Ziv@med.va.gov FU Department of Veterans Affairs FX This work was supported by the Department of Veterans Affairs. NR 13 TC 13 Z9 13 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD MAR PY 2005 VL 2 IS 1 SI SI BP S5 EP S15 DI 10.1088/1741-2560/2/1/002 PG 11 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA V43HJ UT WOS:000209672200002 PM 15876655 ER PT J AU Zimmerman, MA Goumnerova, LC Proctor, M Scott, RM Marcus, K Pomeroy, SL Turner, CD Chi, SN Chordas, C Kieran, MW AF Zimmerman, MA Goumnerova, LC Proctor, M Scott, RM Marcus, K Pomeroy, SL Turner, CD Chi, SN Chordas, C Kieran, MW TI Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE atypical teratoid rhabdoid tumor (AT/RT); brain tumor; pediatric; rhabdoid; treatment ID MALIGNANT RHABDOID TUMOR; OF-THE-LITERATURE; TERATOID TUMOR; INTRATHECAL METHOTREXATE; PATHOLOGICAL FINDINGS; VINCRISTINE THERAPY; BRAIN; CHILD; INFANCY; FEATURES AB Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant lesions of childhood that carry a very poor prognosis. AT/RT can occur in the central nervous system (CNS AT/RT) and disease in this location carries an even worse prognosis with a median survival of 7-months. In spite of multiple treatment regimens consisting of maximal surgical resection (including second look surgery), radiation therapy (focal and craniospinal), and multi-agent intravenous, oral and intrathecal chemotherapy, with or without high-dose therapy and stem cell rescue, only seven long-term survivors of CNS AT/RT have been reported, all in patients with newly diagnosed disease. For this reason, many centers now direct such patients, particularly those under 5-years of age, or those with recurrent disease, towards comfort care rather than attempt curative therapy. We now report on four children, two with newly diagnosed CNS AT/RT and two with progressive disease after multi-agent chemotherapy who are long term survivors (median follow-up of 37-months) using a combination of surgery, radiation therapy, and intensive chemotherapy. The chemotherapy component was modified from the Intergroup Rhabdomyosarcoma Study Group (IRS III) parameningeal protocol as three of the seven reported survivors in the literature were treated using this type of therapy. Our four patients, when added to the three reported survivors in the literature using this approach, suggest that patients provided this aggressive therapy can significantly alter the course of their disease. More importantly, we report on the first two survivors after relapse with multi-agent intravenous and intrathecal chemotherapy treated with this modified regimen. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Kieran, MW (reprint author), Rm SW331,Rm Binney St, Boston, MA 02115 USA. EM mkieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 58 TC 50 Z9 54 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAR PY 2005 VL 72 IS 1 BP 77 EP 84 DI 10.1007/s11060-004-3115-y PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 914BW UT WOS:000228200600012 PM 15803379 ER PT J AU Bohnen, NI Kaufer, DI Hendrickson, R Ivanco, LS Lopresti, BJ Koeppe, RA Meltzer, CC Constantine, G Davis, JG Mathis, CA DeKosky, ST Moore, RY AF Bohnen, NI Kaufer, DI Hendrickson, R Ivanco, LS Lopresti, BJ Koeppe, RA Meltzer, CC Constantine, G Davis, JG Mathis, CA DeKosky, ST Moore, RY TI Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; IN-VIVO; CHOLINESTERASE-INHIBITORS; CHOLINERGIC SYSTEM; HUMAN BRAIN; PET; PROPIONATE; THERAPY; MEMORY AB Objectives: To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy. Methods: Cognitive and N-[C-11]methyl-piperidin-4-yl propionate ([C-11]PMP) AChE positron emission tomography (PET) assessments before and after donepezil therapy. Results: Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t= -7.9; p<0.0001). Enzyme inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t= -14.1; p<0.0001). Donepezil induced cortical inhibition of AChE activity correlated with changes in the Stroop Color Word interference scores (R-2 = 0.59, p<0.01), but not with primary memory test scores. Analysis of the Stroop test data indicated that subjects with AChe inhibition greater than the median value (<22.2%) had improved scores on the Stroop Color Word Test compared with subjects with less inhibition who had stable to worsening scores (t= -2.7; p<0.05). Conclusions: Donepezil induced inhibition of cortical AChE enzyme activity is modest in patients with mild AD. The degree of cortical enzyme inhibition correlates with changes in executive and attentional functions. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Dept Math & Stat, Pittsburgh, PA 15260 USA. RP Bohnen, NI (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Liliane S Kaufmann Bldg,Suite 811,3471 5th Ave, Pittsburgh, PA 15213 USA. EM nbohnen@pitt.edu RI Mathis, Chester/A-8607-2009 FU NIA NIH HHS [AG05133] NR 35 TC 86 Z9 87 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAR PY 2005 VL 76 IS 3 BP 315 EP 319 DI 10.1136/jnnp.2004.038729 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 901TM UT WOS:000227304800005 PM 15716518 ER PT J AU Smith, AC Stefani, MR Moghaddam, B Brown, EN AF Smith, AC Stefani, MR Moghaddam, B Brown, EN TI Analysis and design of Behavioral experiments to characterize population learning SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RANDOM-EFFECTS MODELS; PREFRONTAL CORTEX; DYNAMIC-ANALYSIS; LESIONS; RATS; SET; ACQUISITION; MEMORY AB In population learning studies, between-subject response differences are an important source of variance that must be characterized to identify accurately the features of the learning process common to the population. Although learning is a dynamic process, current population analyses do not use dynamic estimation methods, do not compute both population and individual learning curves, and use learning criteria that are less than optimal. We develop a state-space random effects (SSRE) model to estimate population and individual learning curves, ideal observer curves, and learning trial,,, and to make dynamic assessments of learning between two populations and within the same population that avoid multiple hypothesis tests. In an 80-trial Study of an NMDA antagonist's effect on the ability of rats to execute a set-shift task, Our dynamic assessments of learning demonstrated that both the treatment and control groups learned, yet, by trial 35, the treatment group learning was significantly impaired relative to control. We used our SSRE model in a theoretical study to evaluate the design efficiency of learning experiments in terms of the number of animals per group and number of trials per animal required to characterize learning differences between two populations. Our results demonstrated that a maximum difference in the probability of a correct response between the treatment and control group learning Curves of 0.07 (0.20) would require 15 to 20 (5 to 7) animals per group in an 80 (60)-trial experiment. The SSRE model offers a practical approach to dynamic analysis of population learning and a theoretical framework for optimal design of learning experiments. C1 Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Cambridge, MA USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM brown@neurostat.mgh.harvard.edu FU NIDA NIH HHS [DA-015644]; NIMH NIH HHS [MH-61637, MH-48404, MH-65026, MH-59733] NR 32 TC 21 Z9 21 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2005 VL 93 IS 3 BP 1776 EP 1792 DI 10.1152/jn.00765.2004 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 901AX UT WOS:000227256500055 PM 15456798 ER PT J AU Paul, RH Brickman, AM Navia, B Hinkin, C Malloy, PF Jefferson, AL Cohen, RA Tate, DF Flanigan, TP AF Paul, RH Brickman, AM Navia, B Hinkin, C Malloy, PF Jefferson, AL Cohen, RA Tate, DF Flanigan, TP TI Apathy is associated with volume of the nucleus accumbens in patients infected with HIV SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FRONTAL-SUBCORTICAL CIRCUITS; BASAL GANGLIA; HUMAN BRAIN; DEMENTIA; PROTEINS; ADULTS; AIDS AB Apathy refers to a reduction in self-initiated behavior, and it is commonly reported by patients infected with human immunodeficiency virus (HIV). It remains unclear whether apathy among HIV patients reflects a direct effect of the virus on subcortical brain circuits or a secondary neuropsychiatric symptom. In the present study we examined the relationship between ratings of apathy and quantitative analysis of the nucleus accumbens (NA), a subcortical brain structure that regulates initiation of behavioral activation. Twelve HIV-positive individuals without dementia were administered the Marin Apathy Scale and underwent neuroimaging. Voxel-based quantification of the nucleus accumbens was completed using a segmentation protocol. Results of our study revealed that increased ratings of apathy were significantly correlated with lower volume of the nucleus accumbens. By contrast, ratings of depression were unrelated to either apathy or nucleus accumbens volume. These findings provide preliminary evidence that apathy reflects direct involvement of the central nervous system in patients with HIV. C1 Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA. Tufts Univ, Dept Psychiat & Neurol, Boston, MA 02111 USA. Brown Med Sch, Dept Med, Providence, RI USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Systemepartment, Los Angeles, CA USA. RP Paul, RH (reprint author), Brown Med Sch, Ctr AIDS Res, Ctr Behav & Prevent Med, 1 Hoppin St, Providence, RI 02903 USA. EM RPaul@Lifespan.org RI Tate, David/G-5166-2011; Tate, David/I-3963-2013 OI Tate, David/0000-0003-0213-1920; FU NIA NIH HHS [F32 AG022773, F32 AG022773-01, R01 AG017975, F32 AG022773-02, P30 AG013846, P30 AG013846-05]; NIDA NIH HHS [R03DA15045-01, T32 DA013911, T32DA13911]; NIMH NIH HHS [K23 MH065857, K23MH65857, K23MH65857-01]; NINDS NIH HHS [R01 NS036524, NS36524] NR 27 TC 50 Z9 53 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2005 VL 17 IS 2 BP 167 EP 171 DI 10.1176/appi.neuropsych.17.2.167 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 932GA UT WOS:000229541000005 PM 15939969 ER PT J AU Erickson, JI Ditomassi, M AF Erickson, JI Ditomassi, M TI The clinical nurse leader: New in name only SO JOURNAL OF NURSING EDUCATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Erickson, JI (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 8 Z9 8 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD MAR PY 2005 VL 44 IS 3 BP 99 EP 100 PG 2 WC Nursing SC Nursing GA 904YE UT WOS:000227533700001 PM 15787017 ER PT J AU Lopez-Garcia, E Schulze, MB Meigs, JB Manson, JAE Rifai, N Stampfer, MJ Willett, WC Hu, FB AF Lopez-Garcia, E Schulze, MB Meigs, JB Manson, JAE Rifai, N Stampfer, MJ Willett, WC Hu, FB TI Consumption of Trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction SO JOURNAL OF NUTRITION LA English DT Article DE trans fatty acids; inflammation; endothelial dysfunction; Nurses' Health Study ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; SELF-ADMINISTERED QUESTIONNAIRE; DIETARY-FAT; CARDIOVASCULAR-DISEASE; HEALTHY-MEN; LIPOPROTEIN CHOLESTEROL; ADIPOSE-TISSUE; RISK; WOMEN AB Trans fatty acid intake has been associated with a higher risk of cardiovascular disease. The relation is explained only partially by the adverse effect of these fatty acids on the lipid profile. We examined whether trans fatty acid intake could also affect biomarkers of inflammation and endothelial dysfunction including C-reactive protein (CRIP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR-2), E-selectin, and soluble cell adhesion molecules (sICAM-1 and sVCAM-1). We conducted a cross-sectional study of 730 women from the Nurses' Health Study I cohort, aged 43-69 y, free of cardiovascular disease, cancer, and diabetes at time of blood draw (1989-1990). Dietary intake was assessed by a validated FFQ in 1986 and 1990. CRP levels were 73% higher among those in the highest quintile of trans fat intake, compared with the lowest quintile. IL-6 levels were 17% higher, sTNFR-2 5%, E-selectin 20%, sICAM-1 10%, and sVCAM-1 levels 10% higher. Trans fatty acid intake was positively related to plasma concentration of CRP (P = 0.009), sTNFR-2 (P = 0.002), E-selectin (P = 0.003), slCAM-1 (P = 0.007), and sVCAM-1 (P = 0.001) in linear regression models after controlling for age, BMI, physical activity, smoking status, alcohol consumption, intake of monounsaturated, polyunsaturated, and saturated fatty acids, and postmenopausal hormone therapy. In conclusion, this study suggests that higher intake of trans fatty acids could adversely affect endothelial function, which might partially explain why the positive relation between trans fat and cardiovascular risk is greater than one would predict based solely on its adverse effects on lipids. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Gen Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Div Prevent Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Lab Med, Childrens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Lopez-Garcia, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. EM elopezga@hsph.harvard.edu FU NCI NIH HHS [CA 87969]; NIDDK NIH HHS [DK 55523] NR 33 TC 261 Z9 281 U1 8 U2 33 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 2005 VL 135 IS 3 BP 562 EP 566 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 904PF UT WOS:000227509500032 PM 15735094 ER PT J AU Counter, SA Buchanan, LH Ortega, F AF Counter, SA Buchanan, LH Ortega, F TI Neurocognitive impairment in lead-exposed children of Andean lead-glazing workers SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID BLOOD LEAD; NEUROBEHAVIORAL DEVELOPMENT; COGNITIVE FUNCTION; INTOXICATION; INTELLIGENCE; PERFORMANCE; EXPOSURES; DEFICITS; SUCCIMER; INFANCY AB Objective: The level of lead (Pb) exposure necessary to induce intellectual impairment has not been firmly established. Some studies using conventional language-based intelligence tests have reported that pediatric blood lead (PbB) levels lower than 10 mu g/dL (0.483 mu mol/L) are associated with neurocognitive impairment. However, these tests may introduce cultural biases in the assessment of intellectual functioning: The objective of this study was to assess the effects of PbB concentration on nonverbal intelligence in Andean children with chronic environmental Pb exposure using a nonlanguage-based test of cognitive functioning Methods: Using Raven Colored Progressive Matrices (RCPM) as a measure of nonverbal intelligence, this study investigated the effects of Pb exposure (biomarker: PbB levels) on intellectual functioning in 188 chronically Pb-exposed children (age range: 5.33-11.67 years) of Ecuadorian Andean Pb-glazing workers. Results: The mean PbB level of the 188 children was 29.3 mu g/dL (range: 3.5-94.3 mu g/dL). Forty-seven children had PbB levels < 10 mu g/dL (Centers for Disease Control and Prevention [CDC] I classification), of which 30 had abnormal (ie, <= 25th percentile) RCPM standard scores. Of the 141 children with PbB levels >= 10 mu g/dL, 97 had abnormal RCPM scores. A regression analysis revealed a statistically significant negative association (r = -0.331, P < 0.0001) between PbB level and RCPM standard score. Conversion of RCPM standard scores to estimated IQ scores showed an approximate two point decrease in IQ for each 10-mu g/dL increment in PbB level from 10 to > 70 mu g/dL. Conclusions: Performance on a test of nonverbal intelligence was inversely associated with chronic Pb exposure in Andean children with PbB levels below and above the CDC risk management level of 10 mu g/dL, with the decline in test scores suggesting a dose-response relationship. C1 Harvard Univ, Sch Med, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Massachusetts, Dept Pediat, Shriver Ctr, Sch Med, Waltham, MA USA. Harvard Univ, Hlth Serv, Dept Audiol, Cambridge, MA 02138 USA. Univ San Francisco, Dept Med, Quito, Ecuador. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu NR 37 TC 29 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 2005 VL 47 IS 3 BP 306 EP 312 DI 10.1097/01.jom.0000155717.45594.65 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 905NH UT WOS:000227574900014 PM 15761328 ER PT J AU Yeshwant, K Seldin, EB Gateno, T Everett, P White, CL Kikinis, R Kaban, LB Troulis, AJ AF Yeshwant, K Seldin, EB Gateno, T Everett, P White, CL Kikinis, R Kaban, LB Troulis, AJ TI Analysis of skeletal movements in mandibular distraction osteogenesis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY OCT 02-05, 2002 CL CHICAGO, IL SP Amer Assoc Oral & Maxillofacial Surg ID OSTEOTOMY; DEVICE; SYSTEM; MODEL AB Purpose: The purpose of this study was to use geometric parameters of movement, calculated from 3-dimensional computed tomography (CT) data, to determine the curvilinear distractor dimensions required to correct mandibular deformities in a series of patients. Materials and Methods: Preoperative CT scans from 15 patients with symmetric (n = 5) and asymmetric (n = 10) deformities were imported into a CT-based software program (Osteoplan; an open-source visualization application developed by Gering et al at the Surgical Planning Laboratory [SPL, Brigham and Women's Hospital, Boston, MA]). The software was used to reconstruct virtual 3-dimensional models from these scans. Two experienced surgeons, working with a computer scientist, then used Osteoplan to create an ideal treatment plan for each patient. In each case, the 3-dimensional curvilinear movement was quantified using 4 "parameters of movement" (POMs). These parameters were then used to prescribe a distraction device capable of executing the planned skeletal correction. Curvilinear distractor dimensions calculated by Osteoplan included the radius of curvature of the prescribed device, and the distractor elongation, pitch, and handedness. Results: Treatment plans including POMs were developed for each patient. The radii of curvature for the prescribed distractors ranged from 2.3 to 14.1 cm, the distractor elongation dimensions ranged from 0.7 to 3.2 cm, and the pitch (horizontal plane) dimensions ranged from 0.005 to 0.8 cm. Handedness was either a left (n = 12) or right (n = 8) turning helix. Conclusion: The results of this study indicate that, using geometric parameters of movement calculated from 3-dimensional CT scans, curvilinear devices could be prescribed for correction of the range of skeletal deformities in this group of patients. (C) 2005 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Harvard Univ, Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. RP Troulis, AJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM mtroulis@partners.org FU NIDCR NIH HHS [K23-DE14080-02] NR 20 TC 23 Z9 23 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2005 VL 63 IS 3 BP 335 EP 340 DI 10.1016/j.joms.2004.06.057 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 901EY UT WOS:000227267000009 PM 15742283 ER PT J AU Li, G DeFrate, LE Rubash, HE Gill, TJ AF Li, G DeFrate, LE Rubash, HE Gill, TJ TI In vivo kinematics of the ACL during weight-bearing knee flexion SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE in vivo kinematics; anterior cruciate ligament ID ANTERIOR CRUCIATE LIGAMENT; FEMORAL TUNNEL PLACEMENT; SITU FORCES; TIBIAL LOADS; RECONSTRUCTION; POSTERIOR; GRAFT; QUADRICEPS; MOTION; JOINT AB No study has investigated the three-dimensional morphological changes of the anterior cruciate ligament (ACL) during functional activities in vivo. The purpose of this study was to analyze the elongation, rotation (twist), and orientation of the ACL during weight-bearing flexion in five human subjects using dual-orthogonal fluoroscopic images and MR image-based computer models. The ACL consistently decreased in length with flexion. At 90 degrees, the length decreased by 10% compared to its length at full extension. The ACL twisted internally by only 20 degrees at 30 degrees of flexion. The ACL was oriented more vertically (approximately 60 degrees) and slightly laterally (approximately 10 degrees) at low flexion angles. These data on in vivo ligament elongation demonstrate that the ACL plays a more important role in lower flexion angles than at higher flexion angles during weight-bearing flexion. These data also suggest that successful ACL reconstruction should not only restore the ligament's elongation behavior, but also its rotational and orientation characteristics, so that normal ACL biomechanics are restored. (c) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GBJ 1215, Boston, MA 02115 USA. EM gli1@partners.org NR 34 TC 81 Z9 88 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2005 VL 23 IS 2 BP 340 EP 344 DI 10.1016/j.orthres.2004.08.006 PG 5 WC Orthopedics SC Orthopedics GA 905KN UT WOS:000227567100016 PM 15734246 ER PT J AU Studer, RK Chu, CR AF Studer, RK Chu, CR TI p38 MAPK and COX2 inhibition modulate human chondrocyte response to TGF-beta SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE p38 MAPK; COX2; TGF-beta; arthritic human chondrocytes ID ACTIVATED PROTEIN-KINASE; HUMAN ARTICULAR CHONDROCYTES; NITRIC-OXIDE; TISSUE INHIBITOR; MATRIX METALLOPROTEINASE-3; CULTURED CHONDROCYTES; SELECTIVE INHIBITOR; CELL-PROLIFERATION; PROSTAGLANDIN E-2; GENE-EXPRESSION AB These studies compare actions of p38 MAPK inhibition and COX2 inhibition to modulate human arthritic chondrocyte responses to TGF-beta and FCS under basal and IL-1 activated conditions. Chondrocytes isolated from arthritic human femoral condyle cartilage obtained at total knee replacement were grown to 80% confluence. Proteoglycan synthesis and proliferation were measured with and without IL-1 activation in the presence and absence of growth factors and with and without inhibition of p38 MAPK or COX2 activity. Experiments to evaluate TIMP-1 production under these conditions were done using cartilage organ cultures. Neither p38 MAPK inhibitors nor COX2 inhibition affected basal proliferation. However both inhibitors enhanced the proliferative response to TGF-beta and FCS in IL-1 activated chondrocytes. TGF-beta stimulated proteoglycan synthesis was decreased by p38 MAPK inhibition, however COX2 inhibition restored the response to TGF-beta in IL-1 activated cells. In contrast, COX2 inhibition did not modulate TIMP-1 production while p38 MAPK inhibitors potentiated TGF-beta stimulated production of TIMP-1 in IL-1 activated cartilage. p38 MAPK inhibition and COX2 inhibition have unique and similar abilities to counteract some of the effects of IL-1 on human chondrocyte/cartilage metabolism. Both will partially restore the proliferative response to growth factors. p38 MAPK inhibition blunts TGF-beta stimulation of proteoglycan synthesis, but increases TIMP-1 synthesis. COX2 inhibition can restore the proteoglycan synthetic response to TGF-beta, but has no effect on cartilage TIMP-1 production. Use of these inhibitors to minimize cartilage damage in arthritic and mechanically stressed joints should reflect these characteristics. Published by Elsevier Ltd. on behalf of Orthopaedic Research Society. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Med Ctr, Pittsburgh, PA USA. Dept Orthopaed Surg, Ferguson Lab, Pittsburgh, PA USA. RP Studer, RK (reprint author), Vet Adm Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. EM rstuder@pitt.edu NR 33 TC 18 Z9 18 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAR PY 2005 VL 23 IS 2 BP 454 EP 461 DI 10.1016/j.orthres.2004.08.012 PG 8 WC Orthopedics SC Orthopedics GA 905KN UT WOS:000227567100032 PM 15734262 ER PT J AU Perez, A Duxbury, M Rocha, FG Ramsanahie, AP Farivar, RS Varnholt, H Ito, H Wong, H Rounds, J Zinner, MJ Whang, EE Ashley, SW AF Perez, A Duxbury, M Rocha, FG Ramsanahie, AP Farivar, RS Varnholt, H Ito, H Wong, H Rounds, J Zinner, MJ Whang, EE Ashley, SW TI Glucagon-like peptide 2 is an endogenous mediator of postresection intestinal adaptation SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID SHORT-BOWEL SYNDROME; EPITHELIAL PROLIFERATION; GROWTH; EXPRESSION; RATS AB Background: After massive small bowel resection, the remnant intestine undergoes compensatory adaptation. We tested the hypothesis that glucagon-like peptide-2 (GLP-2) is an endogenous mediator of postresection intestinal adaptation. Methods: Rats were allocated to 1 of 4 groups: groups 1 and 2 rats underwent mid-small bowel transection and reanastomosis; groups 3 and 4 rats underwent 75% mid-small bowel resection and reanastomosis. Groups 2 and 4 rats were administered 1.8 mg of antirat GLP-2 antibody twice daily beginning immediately after the surgical procedure; groups 1 and 3 rats were administered rabbit serum (control). Real specimens were harvested on postoperative day 7. Results: Real mucosa from group 3 animals displayed morphologic and proliferative indices of adaptation. Each of these indices of adaptation was inhibited by GLP-2 immunoneutralization (group 4). Morphologic and proliferative parameters in the ileum from animals that had undergone transection with reanastomosis were unaffected by GLP-2 immunoneutralization. Conclusions: These results suggest that GLP-2 is an endogenous mediator of postresection intestinal adaptation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. RP Ashley, SW (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM sashley@partners.org FU NIDDK NIH HHS [DK02786, DK47326] NR 21 TC 15 Z9 19 U1 0 U2 0 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAR-APR PY 2005 VL 29 IS 2 BP 97 EP 101 DI 10.1177/014860710502900297 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 907GZ UT WOS:000227705600007 PM 15772387 ER PT J AU Gordon, LB Harten, IA Patti, ME Lichtenstein, AH AF Gordon, LB Harten, IA Patti, ME Lichtenstein, AH TI Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: Clues to the biology of premature atherosclerosis in Hutchinson-Gilford Progeria Syndrome SO JOURNAL OF PEDIATRICS LA English DT Article ID PATHOLOGIC FINDINGS; INSULIN-RESISTANCE; SERUM ADIPONECTIN; HEART-DISEASE; HYPOADIPONECTINEMIA; LIPODYSTROPHIES; MUTATIONS; APOPTOSIS; EVENTS; PLASMA AB Objectives Children with Hutehinson-Gilford Progeria Syndrome (HGPS) die of severe premature atherosclerosis at an average age of 13 years. Although the LMNA gene defect responsible for this "premature aging syndrome" has been identified, biological mechanisms underlying the accelerated atherosclerosis are unknown. We determined whether children with HGPS demonstrate abnormalities in known biomarkers for cardiovascular disease (CVD) risk. Study design We quantified serum lipids, lipoproteins, C-reactive protein (CRP), and adiponectin in children with HGPS and age-matched control children. Results HDL cholesterol (P < .0001) and adiponectin (P < .001) concentrations decreased significantly with increasing age in HGPS but not in control children. There was a positive correlation between these variables in HGPS (P < .0001) but not control children. Mean total cholesterol, LDL and HDL cholesterol. triglyceride, and median CRP levels were similar between HGPS and control children (all P > .05). Conclusions Declining HDL cholesterol and adiponectin with advancing age may contribute to accelerated atherosclerotic plaque formation in HGPS. Several factors frequently associated with CVD risk in normal aging (elevated CRP, total and LDL cholesterol) showed no difference and are unlikely to influence CVD risk in HGPS. HDL and adiponectin may represent significant mediators and potential therapeutic targets for atherosclerosis in HGPS. C1 Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. Rhode Isl Hosp, Dept Pediat, Providence, RI USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Tufts Univ, Cardiovasc Nutr Lab, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Gordon, LB (reprint author), Tufts Univ, Sch Med, Dept Anat & Cellular Biol, 136 Harrison Ave,Stearns Bldg,Room 610, Boston, MA 02111 USA. FU NHLBI NIH HHS [R01-HL-58008, HL-54727]; NIA NIH HHS [1-R21-AG021902-01]; NIDDK NIH HHS [DK060837, R01-DK62948] NR 39 TC 29 Z9 29 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2005 VL 146 IS 3 BP 336 EP 341 DI 10.1016/j.jpeds.2004.10.064 PG 6 WC Pediatrics SC Pediatrics GA 906SI UT WOS:000227662600012 PM 15756215 ER PT J AU Buerhaus, PI Donelan, K Norman, L Dittus, R AF Buerhaus, PI Donelan, K Norman, L Dittus, R TI Nursing students' perceptions of a career in nursing and impact of a national campaign designed to attract people into the nursing profession SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article AB The study assessed perceptions about a career in nursing, the nursing shortage, decision to enroll in a nursing education program, and awareness and effect of the Johnson & Johnson Campaign for Nursing's Future. Data were obtained from a survey administered to a national sample of 496 nursing students. Although most students believe nursing is physically challenging and there is inadequate respect and recognition of nurses, most agree nursing is a good career for men and for people who have academic ability and want a secure job. Although the majority believes the nursing shortage will increase stress on nurses, lower the quality of care, and fail to improve working conditions, most students also expect the shortage will lead to higher pay and more job choices. Information and advice from practicing nurses was the most influential factor in deciding to become a nurse, and friends, parents, and other family members also had a positive influence. Two thirds are aware of the campaign, almost all said it made them feel good about becoming a nurse, and students who are White and enrolled in baccalaureate programs were more likely to be aware of the campaign. Future recruitment initiatives should strengthen the focus on men and minorities, parents and friends, and practicing nurses and nursing educators. (c) 2005 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Med Ctr, Div Gen Internal Med, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Ctr Hlth Serv Res, Nashville, TN USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Sch Nursing, 512 Godchaux Hall,21st Ave S, Nashville, TN 37240 USA. EM peter.buerhaus@vanderbilt.edu NR 21 TC 23 Z9 23 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 8755-7223 J9 J PROF NURS JI J. Prof. Nurs. PD MAR-APR PY 2005 VL 21 IS 2 BP 75 EP 83 DI 10.1016/j.profnurs.2005.02.001 PG 9 WC Nursing SC Nursing GA 919HL UT WOS:000228608900003 PM 15806504 ER PT J AU Peery, JT Ledoux, WR Klute, GK AF Peery, JT Ledoux, WR Klute, GK TI Residual-limb skin temperature in transtibial sockets SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputation; artificial limbs; biomechanics; heat transfer; prosthetics; rehabilitation; residual limb; skin temperature; transtibial sockets; veterans ID FRICTION AB The insulated environment of the lower-limb prosthesis can result in elevated residual-limb skin temperatures that may contribute to skin initation, blistering, and a reduced quality of life. The design and materials of the prosthetic socket, suspension system, and liner can potentially alleviate these conditions, but the thermal load may vary with activity and location within the socket. To characterize the thermal environment at the skin-prosthesis interface, we made temperature measurements on five transtibial amputees at 14 locations on the residual limbs. After the participants donned their prosthesis and rested in the seated position for 15 min, the mean skin temperatures of their residual limbs increased by 0.8 degrees Celcius. Subsequent walking for 10 min resulted in a 1.7 degrees Celsius total increase in mean skin temperature. Thermal contour maps revealed the skin was coolest at the interior proximal location and warmest across the posterior section, con-elating with areas of low and high perfusion. From the results, we determined that residual-limb skin temperature depends on activity and locality. This information may aid in understanding where and why skin problems develop on lower-limb residual limbs and may provide design requirements for new prosthetic socket systems intended to alleviate temperature-related discomfort. C1 VA Puget Sound, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA 98108 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Klute, GK (reprint author), VA Puget Sound, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, 1660 S Columbian Way,MS-151, Seattle, WA 98108 USA. EM gklute@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 9 TC 23 Z9 23 U1 0 U2 13 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 MAR-APR PY 2005 VL 42 IS 2 BP 147 EP 154 DI 10.1682/JRRD.2004.01.0013 PG 8 WC Rehabilitation SC Rehabilitation GA 935TT UT WOS:000229807000004 PM 15944879 ER PT J AU Cavanaugh, JT Goldvasser, D McGibbon, CA Krebs, DE AF Cavanaugh, JT Goldvasser, D McGibbon, CA Krebs, DE TI Comparison of head- and body-velocity trajectories during locomotion among healthy and vestibulopathic subjects SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE bilateral vestibular hypofunction; equilibrium; high curvature analysis; locomotion; locomotor control; measurement; postural control; rehabilitation; unilateral vestibular hypofunction; vestibulocollic; vestibulopathy ID VESTIBULAR REHABILITATION; SPACE-FLIGHT; CONTROL STRATEGIES; DYNAMIC STABILITY; STABILIZATION; COORDINATION; BALANCE; WALKING; COMPLEXITY; DEFICITS AB The optimal strategies for improving locomotor stability in people with vestibulopathy remain unclear. To help identify likely targets for intervention, we sought to determine whether vestibulopathic postural control impairment during locomotor activity was more localized to either the head or the whole body. We used high curvature analysis (HCA) to quantify the smoothness of head- and body-velocity trajectories during repeated stepping in 18 vestibulopathic and 17 healthy subjects. We employed a mixed-model repeated measures analysis of variance to compare differences in head- and body-trajectory HCA scores. Pearson coefficients were used to describe relationships between head- and body-trajectory HCA scores within each group. The results revealed that neither head- nor body-velocity trajectories were relatively more impaired in subjects with vestibulopathy. Importantly, however, the smoothness of head and body trajectories was more strongly related in subjects with vestibulopathy compared with healthy subjects, suggesting that the fundamental motor control impairment produced by vestibulopathy may be related to an abnormal coupling of head and body motion. We discuss implications for locomotor training in patients with vestibulopathy. C1 Dept Vet Affairs Med Ctr, GRECC 182, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Phys & Occupat Therapy, Durham, NC USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Univ New Brunswick, Dept Kinesiol, Fredericton, NB, Canada. Univ New Brunswick, Inst Biomed Engn, Fredericton, NB, Canada. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA 02115 USA. RP Cavanaugh, JT (reprint author), Dept Vet Affairs Med Ctr, GRECC 182, 508 Fulton St, Durham, NC 27705 USA. EM jimcavanaugh@nc.rr.com FU NCCIH NIH HHS [R21AT00553]; NIA NIH HHS [R01AG11255] NR 41 TC 7 Z9 7 U1 0 U2 0 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 MAR-APR PY 2005 VL 42 IS 2 BP 191 EP 198 DI 10.1682/JRRD.2004.01.0005 PG 8 WC Rehabilitation SC Rehabilitation GA 935TT UT WOS:000229807000009 PM 15944884 ER PT J AU Goldstein, G Haas, GL Shemansky, WJ Barnett, B Salmon-Cox, S AF Goldstein, G Haas, GL Shemansky, WJ Barnett, B Salmon-Cox, S TI Rehabilitation during alcohol detoxication in comorbid neuropsychiatric patients SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE attention control condition; cognitive rehabilitation; comorbid alcohol abuse; detoxication; dual diagnosis; intervention; memory; neuropsychology; rehabilitation; veteran ID RECOVERY AB For this study, we evaluated the effectiveness of a cognitive training program in improving cognitive function in patients with alcoholism comorbid with another neuropsychiatric disorder and going through the subacute phase of detoxication. We employed a randomized clinical trial design in which 20 subjects were assigned to a five-session cognitive rehabilitation program and 20 subjects were assigned to an attention placebo control condition. All subjects received a battery of cognitive tests for reasoning, attention, and visual-spatial abilities. These tests were repeated at the completion of the study. The training consisted of a number of component tasks designed to improve attention, speed of information processing, perceptual analysis, and visual-spatial cognition. We plotted performance on training results across sessions to detect evidence of learning effects. Comparisons of the cognitive tests revealed greater improvement in the training as compared to the attention placebo group on measures of attention and conceptual flexibility. We concluded that the training produced significant improvement over and above natural recovery during detoxication. C1 Pittsburgh Healthcare Syst, Vet Integrated Serv Network Mental Illness Res Ed, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Clin, Dept Vet Affairs, Pittsburgh, PA 15206 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Ctr Clin, Dept Vet Affairs, 7180 Highland Dr 151 R, Pittsburgh, PA 15206 USA. EM ggold@nb.net NR 17 TC 10 Z9 10 U1 0 U2 0 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 MAR-APR PY 2005 VL 42 IS 2 BP 225 EP 234 DI 10.1682/JRRD.2004.03.0040 PG 10 WC Rehabilitation SC Rehabilitation GA 935TT UT WOS:000229807000012 PM 15944887 ER PT J AU Gardella, C Johnson, KM Dobie, DJ Bradley, KA AF Gardella, C Johnson, KM Dobie, DJ Bradley, KA TI Prevalence of hysterectomy and associated factors in women veterans affairs patients SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE hysterectomy; veterans hospitals; veterans ID FEMALE VETERANS; SEXUAL ASSAULT; UNITED-STATES; PRIMARY-CARE; HEALTH-CARE; OUTPATIENTS; MILITARY; ABUSE AB OBJECTIVE: To estimate the prevalence of hysterectomy and associated factors in women veterans who access care at a Veterans Affairs medical center. STUDY DESIGN: A survey that included questions regarding hysterectomy status, demographics, medical history and validated mental health measures was mailed to 1,935 women who received care at the VA Puget Sound Health Care System between October 1996 and January 1998. RESULTS: The overall prevalence of hysterectomy was 32%, with 12% of 18-39-year-olds, 35% of 40-49-year-olds, and 57% of women 50 years old or older reporting having had a hysterectomy. In multivariable analyses, older age (OR 1.1, 95% CI 1.07-1.09), multiparity (OR 1.6, 1.14-2.2), self-reported polycystic ovary syndrome (OR 3.3, 1.81-5.9), chronic pelvic pain (OR 3.2, 2.1-4.9), irritabie bowel syndrome (OR 1.8,1.3-3.1) and premenstrual syndrome (OR 1.6, 1.1-2.3) were associated with prior hysterectomy. When factors associated with posttraumatic stress disorder in this population were omitted from the model, age (OR 1.07, 1.05-1.08), multiparity (OR 1.4, 1.0-1.9), a family history of ovarian cancer (OR 1.8, 1.2-2.8) and posttraumatic stress disorder (OR 1.4, 1.02-1.87) were associated with prior hysterectomy. CONCLUSION: The prevalence of hysterectomy may be higher among women veterans as compared with published rates for the general population and may be related to chronic pain syndromes and/or posttraumatic stress disorder. C1 Univ Washington, Med Ctr, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Vet Hlth Adm, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA USA. RP Gardella, C (reprint author), Univ Washington, Med Ctr, Dept Obstet & Gynecol, Box 356460, Seattle, WA 98195 USA. EM cgardel@u.washington.edu FU NIAAA NIH HHS [K23 AA00313] NR 25 TC 9 Z9 9 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 MAR PY 2005 VL 50 IS 3 BP 166 EP 172 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 908ND UT WOS:000227792800003 PM 15841928 ER PT J AU Bloch, DB Yu, JH Yang, WH Graeme-Cook, F Lindor, KD Viswanathan, A Bloch, KD Nakajima, A AF Bloch, Donald B. Yu, Jiang Hong Yang, Wei-Hong Graeme-Cook, Fiona Lindor, Keith D. Viswanathan, Anjali Bloch, Kenneth D. Nakajima, Ayako TI The Cytoplasmic Dot Staining Pattern Is Detected in a Subgroup of Patients with Primary Biliary Cirrhosis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ANTINUCLEAR ANTIBODIES; PRIMARY BILIARY CIRRHOSIS; CYTOPLASMIC AUTOANTIGENS AB Objective. To determine the clinical significance of the cytoplasmic dot anti-"nuclear" antibody (ANA) staining pattern. Methods. We describe a patient with fatigue, arthralgias, elevated serum transaminase, and antibodies staining 5-20 cytoplasmic dots in HEp-2 cells. A liver biopsy revealed the presence of Stage III primary biliary cirrhosis (PBC). Using 2-color immunofluorescence, we determined the relationship between the cytoplasmic dot staining pattern and that produced by antibodies directed against the GW182 component of mRNA processing bodies. To determine the prevalence of the cytoplasmic dot staining pattern in patients with PBC, sera from 493 patients were tested for antibodies producing this staining pattern. Results. Antibodies in our patient's serum colocalized with anti-GW182 antibodies in cytoplasmic dots, but did not react with recombinant GW182, suggesting that they were directed against an additional component(s) of these structures. The cytoplasmic dot staining pattern was observed in 21 of 493 (4.3%) patients with PBC. In comparison, this staining pattern was not produced by serum from 248 patients with other autoimmune diseases. Conclusion. A subset of patients with PBC have autoantibodies that produce the cytoplasmic dot staining pattern. These antibodies react with one or more as yet unidentified components of the mRNA processing body. Appreciation of the clinical significance of the cytoplasmic dot staining pattern may assist in appropriate diagnosis and treatment of patients with PBC. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Serv, Cardiovasc Res Ctr, Boston, MA 02114 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. RP Bloch, DB (reprint author), Massachusetts Gen Hosp East, CNY 149 13th St, Charlestown, MA 02129 USA. EM bloch@helix.mgh.harvard.edu FU Arthritis Foundation; National Institutes of Health [DK-051179, HL-57172]; Harvard Clinical Nutrition Center [DK-40561]; American Heart Association FX Supported by grants from the Arthritis Foundation (DBB), the National Institutes of Health (DK-051179 to DBB, HL-57172 to KDB), and a pilot grant from the Harvard Clinical Nutrition Center (DK-40561). K.D. Bloch was supported by an Established Investigator Award and D.B. Bloch by an Established Investigator Grant from the American Heart Association. NR 19 TC 14 Z9 15 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2005 VL 32 IS 3 BP 477 EP 483 PG 7 WC Rheumatology SC Rheumatology GA V40ON UT WOS:000209488000015 PM 15742439 ER PT J AU Shannon, SE Schumacher, HR Self, S Brown, AN AF Shannon, Sean E. Schumacher, H. Ralph Self, Sally Brown, Alan N. TI Multicentric Reticulohistiocytosis Responding to Tumor Necrosis Factor-alpha Inhibition in a Renal Transplant Patient SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE HISTIOCYTOSIS; NON-LANGERHANS CELL; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANT; RECEPTORS; TUMOR NECROSIS FACTOR AB Multicentric reticulohistiocytosis (MRH) is a rare systemic disease that characteristically produces severe erosive arthritis of the distal and proximal interphalangeal joints along with cutaneous nodules over the upper extremities and face, but it can be found in other organs. There is no known etiology, and it often remits spontaneously within 5-10 years, but can result in severe disfigurement. The diagnosis is made when histologic analysis of involved synovium or cutaneous nodules reveals characteristic histopathology. We describe a case of MRH manifesting as erosive arthritis that developed despite immunosuppressive therapy. Based on studies reporting tumor necrosis factor-alpha (TNF-alpha) positive cells within MRH lesions, we began treatment with TNF-alpha inhibition. Within 2 months the patient showed dramatic clinical and serologic improvement that was maintained until she stopped treatment secondary to an upper respiratory tract infection. Once treatment was restarted, the symptoms again improved. C1 Med Univ S Carolina, Dept Rheumatol Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Univ Penn, Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. RP Shannon, SE (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912,CSB,POB 250637, Charleston, SC 29425 USA. NR 13 TC 24 Z9 25 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2005 VL 32 IS 3 BP 565 EP 567 PG 3 WC Rheumatology SC Rheumatology GA V40ON UT WOS:000209488000031 PM 15742455 ER PT J AU Kim, DH Clavert, P Warner, JJP AF Kim, DH Clavert, P Warner, JJP TI Displaced periprosthetic humeral fracture treated with functional bracing: A report of two cases SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID MANAGEMENT; SHOULDER; ARTHROPLASTY C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, POB 403,275 Cambridge St, Boston, MA 02114 USA. NR 8 TC 8 Z9 8 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR-APR PY 2005 VL 14 IS 2 BP 221 EP 223 DI 10.1016/j.jse.2004.05.006 PG 3 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 912AA UT WOS:000228048300019 PM 15789019 ER PT J AU Vangel, MG AF Vangel, MG TI A numerical approach to the Behrens-Fisher problem SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE nuisance pararrieter; Welch-Aspin series; Trickett-Welch algorithm; integral equation of the first kind; two-sample problem AB The test of the hypothesis of equal means of two normal populations without assumption on the variances is usually referred to as the Behrens-Fisher Problem. Exact similar tests are known not to exist. However. excellent approximately similar "solutions" are readily available. Of these available tests and corresponding critical regions, those due to Welch, Aspin, and Trickett in the 1940s and 1950s come closest to achieving similarity. This article examines numerically the Welch-Aspin asymptotic series and the related Trickett-Welch integral equation formulations of this problem. Through examples, we illustrate that well-behaved tests can deviate from similarity by an almost incredibly small amount. Despite this, with much more extensive computation than was feasible a half-century ago. we can see irregularities which could be an empirical reflection of the known nonexistance of exact solutions. (C) 2004 Published by Elsevier B.V. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Vangel, MG (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM vangel@gate.nmr.mgh.harvard.edu NR 11 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD MAR 1 PY 2005 VL 130 IS 1-2 BP 341 EP 350 DI 10.1016/j.jspi.2003.10.009 PG 10 WC Statistics & Probability SC Mathematics GA 892IZ UT WOS:000226645200021 ER PT J AU Holzrichter, JF Ng, LC Burke, GJ Champagne, NJ Kallman, JS Sharpe, RM Kobler, JB Hillman, RE Rosowski, JJ AF Holzrichter, JF Ng, LC Burke, GJ Champagne, NJ Kallman, JS Sharpe, RM Kobler, JB Hillman, RE Rosowski, JJ TI Measurements of glottal structure dynamics SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID IMPEDANCE; MODELS AB Low power, radarlike electromagnetic (EM) wave sensors, operating in a homodyne interferometric mode, are being used to measure tissue motions in the human vocal tract during speech. However, when these and similar sensors are used in front of the laryngeal region during voiced speech, there remains an uncertainty regarding the contributions to the sensor signal from vocal fold movements versus those from pressure induced trachea-wall movements. Several signal-source hypotheses are tested by performing experiments with a subject who had undergone tracheostomy, and who still was able to phonate when her stoma was covered (e.g., with a plastic plate). Laser-doppler motion-measurements of the subject's posterior trachea show small tissue movements, about 15 microns, that do not contribute significantly to signals from presently used EM sensors. However, signals from the anterior wall do contribute. EM sensor and air-pressure measurements, together with 3-D EM wave simulations, show that EM sensors measure movements of the vocal folds very well. The simulations show a surprisingly effective guiding of EM waves across the vocal fold membrane, which, upon glottal opening, are interrupted and reflected. These measurements are important for EM sensor applications to speech signal de-noising, vocoding, speech recognition, and diagnostics. (c) 2005 Acoustical Society of America. C1 Lawrence Livermore Natl Lab, Livermore, CA USA. Univ Calif Davis, Calif Dept Appl Sci, Davis, CA 95616 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Easton Peabody Lab, Boston, MA 02114 USA. RP Holzrichter, JF (reprint author), Lawrence Livermore Natl Lab, Livermore, CA USA. EM holzrichter1@llnl.gov NR 31 TC 5 Z9 6 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAR PY 2005 VL 117 IS 3 BP 1373 EP 1385 DI 10.1121/1.1842775 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 905NF UT WOS:000227574700038 PM 15807025 ER PT J AU Newcorn, JH Spencer, TJ Biederman, J Milton, DR Michelson, D AF Newcorn, JH Spencer, TJ Biederman, J Milton, DR Michelson, D TI Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE atomoxetine; attention-deficit/hyperactivity disorder; oppositional defiant disorder ID DEFICIT HYPERACTIVITY DISORDER; NOREPINEPHRINE UPTAKE; CLINICAL-TRIAL; ADHD; PLACEBO; CONDUCT; METHYLPHENIDATE; NORTRIPTYLINE; DESIPRAMINE; TOMOXETINE AB Objective: To examine (1) moderating effects of oppositional defiant disorder (ODD) on attention-cleficit/hyperactivity disorder (ADHD) treatment response and (2) responses of ODD symptoms to atornoxetine. Method: Children and adolescents (ages 8-18) with ADHD were treated for approximately 8 weeks with placebo or atornoxetine (fixed dosing: 0.5, 1.2, or 1.8 mg/kg/day, b.i.d.) under randomized, double-blind conditions. Among patients with lifetime diagnostic information (n = 293), 39% were diagnosed with comorbid ODD and 61 % were not. Treatment-group differences and differences between patients with and without comorbid ODD were examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder Rating Scale IV-Parent version, investigator-administered and -scored; Conners' Parent Rating Scale-Revised Short Form; Clinical Global Impressions Severity of ADHD Scale; and the parent-rated Child Health Questionnaire. Results: Youths with ADHD and comorbid ODD showed statistically significant improvement in ADHD, ODD, and quality-of-life measures. Treatment response was similar in youths with and without ODD, except that the comorbid group showed improvement compared with placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day. In contrast, youths without ODD showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day. Conclusions: Atomoxetine treatment improves ADHD and ODD symptoms in youths with ADHD and ODD, although the comorbid group may require higher doses. J. Am. Acad. ChildAdolesc. Psychiatry, 2005;44(3):240-248. Key Words: atomoxetine, attention-cleficit/hyperactivity disorder, oppositional defiant disorder. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Newcorn, JH (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM jeffrey.newcorn@mssm.edu OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 37 TC 91 Z9 93 U1 2 U2 16 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 MAR PY 2005 VL 44 IS 3 BP 240 EP 248 DI 10.1097/00004583-200503000-00008 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 900EB UT WOS:000227197100008 PM 15725968 ER PT J AU Dadras, SS North, PE AF Dadras, SS North, PE TI Infantile hemangiomas are arrested in early vascular differentiation SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Dermatology CY FEB 18-22, 2005 CL New Orland, LA SP Amer Acad Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2005 VL 52 IS 3 SU 2 BP AB13 EP AB13 PG 1 WC Dermatology SC Dermatology GA 906HT UT WOS:000227632300048 ER PT J AU Kuwahara, T Strasswimmer, J de Boer, J Anderson, R AF Kuwahara, T Strasswimmer, J de Boer, J Anderson, R TI Noninvaswe measurements of the photodamaged human skin in vivo by polarization-sensitwe optical coherence tomography SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Dermatology CY FEB 18-22, 2005 CL New Orland, LA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2005 VL 52 IS 3 SU S BP P163 EP P163 PG 1 WC Dermatology SC Dermatology GA 906HU UT WOS:000227632400646 ER PT J AU Somoano, B Niendorf, KB Sober, A Tsao, H AF Somoano, B Niendorf, KB Sober, A Tsao, H TI The potential impact of genetic counseling and testing on health behaviors of patients at high risk for an inherited predisposition to melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Dermatology CY FEB 18-22, 2005 CL New Orland, LA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2005 VL 52 IS 3 SU S BP P146 EP P146 PG 1 WC Dermatology SC Dermatology GA 906HU UT WOS:000227632400579 ER PT J AU Williams, C AF Williams, C TI Home telehealth consultations: A pilot study to provide specialized nursing care to home health patients SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Dermatology CY FEB 18-22, 2005 CL New Orland, LA SP Amer Acad Dermatol C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2005 VL 52 IS 3 SU S BP P211 EP P211 PG 1 WC Dermatology SC Dermatology GA 906HU UT WOS:000227632400831 ER PT J AU Williams, C AF Williams, C TI A dermatology tele-education collaboration between internal medicine and dermatology residents SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Dermatology CY FEB 18-22, 2005 CL New Orland, LA SP Amer Acad Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol & Partners Telemed, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2005 VL 52 IS 3 SU S BP P99 EP P99 PG 1 WC Dermatology SC Dermatology GA 906HU UT WOS:000227632400391 ER PT J AU Gonzalez, J Williams, JW Noel, PH Lee, S AF Gonzalez, J Williams, JW Noel, PH Lee, S TI Adherence to mental health treatment in a primary care clinic SO JOURNAL OF THE AMERICAN BOARD OF FAMILY PRACTICE LA English DT Article ID MAJOR DEPRESSIVE DISORDER; ANTIDEPRESSANT TREATMENT; TREATMENT GUIDELINES; COMMUNITY PRACTICE; NON-ATTENDANCE; PHYSICIAN; PHARMACOTHERAPY; PATIENT; COMMUNICATION; APPOINTMENTS AB Background: Patient nonadherence is common for the standard mental health treatments in primary care: antidepressants and referrals to specialty mental health treatment. This is one of few studies to prospectively identify predictors of nonadherence. Methods: We observed 95 veterans attending an internal medicine clinic prescribed antidepressant medication or referred to mental health treatment. We collected information on sociodemographic factors, health beliefs, preferences about treatment, past experiences, and treatment knowledge. Results: At 1 month, medication adherence was greater when patients experienced previous pharmacy trouble and traveled for less than 30 minutes to reach the clinic. Appointment attendance improved when patients were ready for treatment, perceived benefits, and saw their physician as collaborative. At 6 months, medication adherence was greater when patients reported a preference for medicine treatment, traveled for less than 30 minutes, and perceived greater benefits. Fewer negative effects from previous mental health treatment improved adherence to appointments. In multivariate analyses examining adherence to all treatments, greater readiness for treatment predicted 1-month adherence, whereas being unmarried and seeing the physician as more collaborative improved 6-month adherence. Conclusions: Adherence to antidepressant medications and to mental health referrals should be examined separately. A brief initial assessment for nonadherence risk factors may identify persons for targeted adherence promoting interventions. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, VERDICT Ctr Excellence, San Antonio, TX 78229 USA. Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Sch Med, Durham, NC USA. RP Gonzalez, J (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gonzalezjm1@uthscsa.edu RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 41 TC 34 Z9 40 U1 0 U2 6 PU AMER BOARD FAMILY PRACTICE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 0893-8652 J9 J AM BOARD FAM PRACT JI J. Am. Board Fam. Pract. PD MAR-APR PY 2005 VL 18 IS 2 BP 87 EP 96 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 911MT UT WOS:000228007900002 PM 15798137 ER PT J AU Dhingra, R Nam, BH Benjamin, EJ Wang, TJ Larson, MG D'Agostino, RB Levy, D Vasan, RS AF Dhingra, R Nam, BH Benjamin, EJ Wang, TJ Larson, MG D'Agostino, RB Levy, D Vasan, RS TI Cross-sectional relations of electrocardiographic QRS duration to left ventricular dimensions - The Framingham Heart Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID BUNDLE-BRANCH-BLOCK; HYPERTROPHY; ACTIVATION; ASYNCHRONY; CRITERIA; FAILURE; DISEASE AB OBJECTIVES The goal of this study was to assess the relations of electrocardiographic QRS duration to left ventricular (LV) measurements in individuals without heart failure (HF) or prior myocardial infarction (MI). BACKGROUND Increased electrocardiographic QRS duration ( greater than or equal to 120 ms) is a marker of ventricular dyssynchrony. METHODS We evaluated the relations of maximal electrocardiographic QRS duration to echocardiographic LV dimensions in 4,534 Framingham Heart study participants (mean age 54 years, 57% women) without prior HF or MI. QRS duration was analyzed as a continuous variable and as categories (< 100, 100 to 119, and greater than or equal to 120 ms). RESULTS In linear regression models, LV mass, end-diastolic dimension, and septal and posterior wall thicknesses were positively related to log-QRS duration, whereas fractional shortening (FS) was inversely related (p < 0.001). There was a significant trend for increasing LV mass and dimensions, and decreasing FS across categories of QRS duration (p < 0.001). Left bundle branch block was associated with higher LV mass and lower FS compared with a normal QRS duration (p < 0.001). CONCLUSIONS In our community-based sample of individuals free of HF and MI, increasing electrocardiographic QRS duration was positively related to LV mass and dimensions, and inversely associated with LV FS. Additional investigations are warranted to elucidate the mechanisms underlying the observed associations. (C) 2005 by the American College of Cardiology Foundation. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Epidemiol & Prevent Med, Sch Med, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL67288, 2K24HL04334, K23HL74077, N01-HC-25195] NR 15 TC 47 Z9 51 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 2005 VL 45 IS 5 BP 685 EP 689 DI 10.1016/j.jacc.2004.11.046 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 901FP UT WOS:000227268700007 PM 15734611 ER PT J AU Buck, T Plicht, B Hunold, P Mucci, RA Erbel, R Levine, RA AF Buck, T Plicht, B Hunold, P Mucci, RA Erbel, R Levine, RA TI Broad-beam spectral Doppler sonification of the vena contracta using matrix-array technology - A new solution for semi-automated quantification of mitral regurgitant flow volume and orifice area SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; WEIGHTED MEAN VELOCITY; VALVULAR REGURGITATION; AORTIC REGURGITATION; CARDIAC-OUTPUT; BLOOD-FLOW; SEVERITY; QUANTITATION; ULTRASOUND; FLOWMETER AB OBJECTIVES The objective of this study was to evaluate broad-beam spectral Doppler sonification of the vena contracta using a matrix-array transducer for quantification of mitral regurgitation (MR). BACKGROUND Noninvasive assessment of the severity of valvular regurgitation remains challenging. A recent technique measures regurgitant flow directly at the vena contracta based on the product of velocity times backscattered Doppler power (proportional to orifice area). That approach, however, has been limited by relatively narrow conventional beamwidths. Matrix-array transducers, recently developed for three-dimensional imaging, can potentially provide broader beams. Therefore, we addressed the hypothesis that deliberate broadening of the Doppler beam can encompass larger regurgitant cross-sectional areas to capture a broader range of regurgitant flows. METHODS A matrix-array transducer system was modified to provide a three-dimensionally expanded spectral Doppler sample volume. Calculations of orifice area, flow rate, and regurgitant stroke volume (RSV) from Doppler power were automated on board a routinely used echocardiographic scanner and tested in vitro. In 24 patients with isolated MR, RSV was compared with magnetic resonance imaging (MRI) mitral inflow minus aortic outflow from phase-velocity maps. RESULTS The calculated flow rate and RSV correlated and agreed well with reference values in vitro (r = 0.98 to 0.99) and in patients (r = 0.93, mean difference 0.4 +/- 3.2 ml, p = NS vs. 0), with sufficient sonification to measure flow orifices up to 0.85 cm in diameter. Agreement with MRI was comparable in 17 patients with central and seven with eccentric jets (p = NS vs. 0). CONCLUSIONS The broad-beam spectral Doppler technique provides accurate, largely automated quantification of regurgitant flow rate and integrated RSV directly at the lesion. The accuracy related to broader sonification is made possible by the new matrix-array transducer design. (C) 2005 by the American College of Cardiology Foundation. C1 Univ Duisburg Gesamthsch, W German Heart Ctr Essen, Dept Cardiol, D-45122 Essen, Germany. Univ Duisburg Gesamthsch, Dept Diagnost & Intervent Radiol, D-45122 Essen, Germany. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Buck, T (reprint author), Univ Duisburg Gesamthsch, W German Heart Ctr Essen, Dept Cardiol, Hufelandstr 55, D-45122 Essen, Germany. EM thomas.buck@uni-essen.de FU NHLBI NIH HHS [R01 HL38176, K24 HL67434, HL53702] NR 42 TC 17 Z9 17 U1 0 U2 0 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 MAR 1 PY 2005 VL 45 IS 5 BP 770 EP 779 DI 10.1016/j.jacc.2004.11.036 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 901FP UT WOS:000227268700020 PM 15734624 ER PT J AU Shlipak, MG Katz, R Fried, LF Jenny, NS Stehman-Breen, CO Newman, AB Siscovick, D Psaty, BM Sarnak, MJ AF Shlipak, MG Katz, R Fried, LF Jenny, NS Stehman-Breen, CO Newman, AB Siscovick, D Psaty, BM Sarnak, MJ TI Cystatin-C and mortality in elderly persons with heart failure. (vol 45, pg 268, 2004) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Correction C1 Univ Calif San Francisco, Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv, Pittsburgh, PA USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Tufts Univ, New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94143 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 2005 VL 45 IS 5 BP 811 EP 811 DI 10.1016/j.acc.2005.01.007 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 901FP UT WOS:000227268700035 ER PT J AU Callahan, CM Kroenke, K Counsell, SR Hendrie, HC Perkins, AJ Katon, W Noel, PH Harpole, L Hunkeler, EM Unutzer, J AF Callahan, CM Kroenke, K Counsell, SR Hendrie, HC Perkins, AJ Katon, W Noel, PH Harpole, L Hunkeler, EM Unutzer, J CA IMPACT Investigators TI Treatment of depression improves physical functioning in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression; physical function; physical disability; collaborative care management ID LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; CHRONIC DISEASE SCORE; PRIMARY-CARE PATIENTS; FUTURE-RESEARCH; ELDERLY-PEOPLE; HEALTH SURVEY; DISABILITY; MANAGEMENT; SYMPTOMS AB OBJECTIVES: To determine the effect of collaborative care management for depression on physical functioning in older adults. DESIGN: Multisite randomized clinical trial. SETTING: Eighteen primary care clinics from eight healthcare organizations. PARTICIPANTS: One thousand eight hundred one patients aged 60 and older with major depressive disorder. INTERVENTION: Patients were randomized to the Improving Mood: Promoting Access to Collaborative Treatment (IMPACT) intervention (n=906) or to a control group receiving usual care (n=895). Control patients had access to all health services available as part of usual care. Intervention patients had access for 12 months to a depression clinical specialist who coordinated depression care with their primary care physician. MEASUREMENTS: The 12-item short form Physical Component Summary (PCS) score (range 0-100) and instrumental activities of daily living (IADLs) (range 0-7). RESULTS: The mean patient age was 71.2, 65% were women, and 77% were white. At baseline, the mean PCS was 40.2, and the mean number of IADL dependencies was 0.7; 45% of participants rated their health as fair or poor. Intervention patients experienced significantly better physical functioning at 1 year than usual-care patients as measured using between-group differences on the PCS of 1.71 (95% confidence interval (CI)=0.96-2.46) and IADLs of -0.15 (95% CI=-0.29 to -0.01). Intervention patients were also less likely to rate their health as fair or poor (37.3% vs 52.4%, P<.001). Combining both study groups, patients whose depression improved were more likely to experience improvement in physical functioning. CONCLUSION: The IMPACT collaborative care model for late-life depression improves physical function more than usual care. C1 Indiana Univ, Ctr Aging Res, Regenstrief Inst Inc, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. Univ Washington, Sch Med, Seattle, WA USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Duke Univ, Sch Med, Durham, NC USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Callahan, CM (reprint author), Indiana Univ, Ctr Aging Res, Regenstrief Inst Inc, 1050 Wishard Blvd,RG6, Indianapolis, IN 46202 USA. EM ccallaha@iupui.edu NR 37 TC 104 Z9 106 U1 7 U2 10 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2005 VL 53 IS 3 BP 367 EP 373 DI 10.1111/j.1532-5415.2005.53151.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 900BG UT WOS:000227189800001 PM 15743276 ER PT J AU Hamel, MB Henderson, WG Khuri, SF Daley, J AF Hamel, MB Henderson, WG Khuri, SF Daley, J TI Surgical outcomes for patients aged 80 and older: Morbidity and mortality from major noncardiac surgery SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE elderly; surgery; outcomes; morbidity; mortality ID CARDIAC OPERATIONS; RISK ADJUSTMENT; CARE; QUALITY; LENGTH; STAY; OCTOGENARIANS; COMPLICATIONS; PROGRAM C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Boston Vet Affairs Healthcare Syst, W Roxbury, MA USA. Tenet Hlth Syst, Dallas, TX USA. RP Hamel, MB (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. EM mhamel@bidmc.harvard.edu NR 22 TC 194 Z9 200 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2005 VL 53 IS 3 BP 424 EP 429 DI 10.1111/j.1532-5415.2005.53159.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 900BG UT WOS:000227189800009 PM 15743284 ER PT J AU Ablon, JS Jones, EE AF Ablon, JS Jones, EE TI On analytic process SO JOURNAL OF THE AMERICAN PSYCHOANALYTIC ASSOCIATION LA English DT Article ID CONTROLLED CLINICAL-TRIALS; PSYCHOANALYTIC PROCESS; THERAPEUTIC ACTION; PSYCHOTHERAPY AB An innovative methodology is presented for identifying and assessing change process in psychoanalytic treatments. Using the Psychotherapy Process Q-set (PQS), a panel of experienced psychoanalysts developed a prototype of an ideal psychoanalytic hour. This prototype was then applied to verbatim transcripts of three archived treatment samples: psychoanalyses, long-term analytic therapies, and brief psychodynamic therapies. The degree to which these treatments fostered an analytic process as represented by the prototype was measured quantitatively. Analytic process was significantly more present in psychoanalyses than in the long-term analytic therapies, which, in turn fostered significantly more analytic process than did brief psychodynamic therapies. The study demonstrates that, given descriptive language that does not represent a particular theoretical perspective, analysts can agree on a definition of analytic process, and that analytic process can be operationalized and quantitatively assessed. A second study demonstrates that despite consensus on its definition, there is not just one proper analytic process; rather, there are change processes unique to each dyad. Two quantitative case studies illustrate how each analytic pair has a unique interaction pattern linked to treatment progress. These dyad-unique "interaction structures" are recurrent, mutually influencing patterns of interaction, the experience, recognition, and comprehension of which appear to be a fundamental component of therapeutic action. A bipersonal model is described that attempts to bridge theories of therapeutic action that focus on insight and self-understanding and those that emphasize the patient's experience of the therapist. C1 Massachusetts Gen Hosp, CPS Inst, Dept Psychiat, Psychotherapy Res Program, Newton, MA 02458 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Ablon, JS (reprint author), Massachusetts Gen Hosp, CPS Inst, Dept Psychiat, Psychotherapy Res Program, 313 Washington St,Suite 402, Newton, MA 02458 USA. EM sablon@sprintpcs.com NR 31 TC 44 Z9 46 U1 4 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-0651 J9 J AM PSYCHOANAL ASS JI J. Am. Psychoanal. Assoc. PD SPR PY 2005 VL 53 IS 2 BP 541 EP 568 PG 28 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 934CA UT WOS:000229683300015 PM 16045166 ER PT J AU Ablon, JS AF Ablon, JS TI Reply to Blatt and Fonagy SO JOURNAL OF THE AMERICAN PSYCHOANALYTIC ASSOCIATION LA English DT Editorial Material ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; CONTROLLED CLINICAL-TRIALS; NATIONAL INSTITUTE; PSYCHOTHERAPY PROCESS; DEPRESSION C1 Massachusetts Gen Hosp, CPS Inst, Newton, MA 02458 USA. RP Ablon, JS (reprint author), Massachusetts Gen Hosp, CPS Inst, 313 Washington St,Suite 400, Newton, MA 02458 USA. EM sablon@sprintpcs.com NR 9 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-0651 J9 J AM PSYCHOANAL ASS JI J. Am. Psychoanal. Assoc. PD SPR PY 2005 VL 53 IS 2 BP 591 EP 595 PG 5 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 934CA UT WOS:000229683300018 ER PT J AU Wei, CC Guo, DF Zhang, SL Ingelfinger, JR Chan, JSD AF Wei, CC Guo, DF Zhang, SL Ingelfinger, JR Chan, JSD TI Heterogenous nuclear ribonucleoprotein F modulates angiotensinogen gene expression in rat kidney proximal tubular cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID INSULIN-RESPONSIVE ELEMENT; PROTEIN-KINASE PATHWAY; RENIN MESSENGER-RNA; HIGH GLUCOSE; HNRNP-F; AMINOTRANSFERASE GENE; BINDING PROTEIN; SEQUENCE; SYSTEM; IDENTIFICATION AB An insulin-responsive element (IRE) in the rat angiotensinogen (ANG) gene promoter that binds to two nuclear proteins with apparent molecular weights of 48 and 70 kD was identified previously from rat immortalized renal proximal tubular cells (IRPTC). The present studies aimed to identify and clone the 48-kD nuclear protein and to define its action on ANG gene expression. Nuclear proteins were isolated from IRPTC and subjected to two-dimensional electrophoresis. The 48-kD nuclear protein was detected by Southwestern blotting and subsequently identified by mass spectrometry, revealing that it was identical to 46-kD heterogeneous nuclear ribonucleoprotein F (hnRNP F), a nuclear protein that binds to TATA-binding protein and associates with RNA polymerase 11 and also interacts with nuclear cap-binding complex. The hnRNP F cDNA was cloned from IRPTC by reverse transcriptase-PCR. Bacterially expressed recombinant hnRNP F bound to the rat ANG-IRE, as revealed by gel mobility shift assay. The addition of polyclonal antibodies against hnRNP F yielded a supershift in gel mobility. Transient transfer of sense and antisense hnRNP F cDNA in IRPTC inhibited and enhanced ANG gene expression, respectively. High glucose stimulated and insulin inhibited hnRNP F expression in IRPTC. Expression studies indicated that hnRNP F is present in the kidney, testis, liver, lung, and brain but not in the spleen. In conclusion, these studies demonstrate that hnRNP F binds to rANG-IRE and modulates renal ANG gene expression, implicating that dysregulation of hnRNP F might affect renin-angiotensin system activation and, subsequently, kidney injury in diabetes. C1 CHU Montreal, Hotel Dieu, Ctr Rech, Montreal, PQ H2W 1T8, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02115 USA. RP Chan, JSD (reprint author), CHU Montreal, Hotel Dieu, Ctr Rech, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU NHLBI NIH HHS [HL 48455] NR 58 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2005 VL 16 IS 3 BP 616 EP 628 DI 10.1681/ASN.2004080715 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 902QQ UT WOS:000227372000010 PM 15659559 ER PT J AU Lindberg, JS Culleton, B Wong, G Borah, MF Clark, RV Shapiro, WB Roger, SD Husserl, FE Klassen, PS Guo, MD Albizem, MB Coburn, JW AF Lindberg, JS Culleton, B Wong, G Borah, MF Clark, RV Shapiro, WB Roger, SD Husserl, FE Klassen, PS Guo, MD Albizem, MB Coburn, JW TI Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in Hemodialysis and peritoneal dialysis: A randomized, double-blind, multicenter study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; PARATHYROID-HORMONE; PHOSPHATE-METABOLISM; MORTALITY RISK; BONE-DISEASE; CALCIUM; CALCIFICATION; RECEPTOR; AMG-073; ASSOCIATION AB Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCI acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH greater than or equal to 300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of less than or equal to 250 pg/ml. During a 10-wk efficacy assessment phase, cinacalcet was more effective than control for PTH reduction outcomes, including proportion of patients with mean iPTH levels less than or equal to 300 pg/ml (46 versus 9%), proportion of patients with greater than or equal to 30% reduction in iPTH from baseline (65 versus 13%), and proportion of patients with greater than or equal to 20, greater than or equal to 40, or greater than or equal to 50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH less than or equal to 300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca x P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca x P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. C1 New Orleans Nephrol Associates, New Orleans, LA USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. Credit Valley Hosp, Mississauga, ON, Canada. Calif Pacific Med Ctr, San Francisco, CA 94115 USA. Our Lady Lourdes RMC, Lafayette, LA USA. Brookdale Plaza Nephrol Associates, Brooklyn, NY USA. Gosford Hosp, Gosford, NSW, Australia. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Lindberg, JS (reprint author), New Orleans Nephrol Associates, 4228 Houma Blvd, Metairie, LA 70006 USA. EM jlindberg@bellsouth.net NR 28 TC 234 Z9 246 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2005 VL 16 IS 3 BP 800 EP 807 DI 10.1681/ASN.2004060512 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 902QQ UT WOS:000227372000029 PM 15689407 ER PT J AU Ripoll, J Yessayan, D Zacharakis, G Ntziachristos, V AF Ripoll, J Yessayan, D Zacharakis, G Ntziachristos, V TI Experimental determination of photon propagation in highly absorbing and scattering media SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DIFFUSION-COEFFICIENT DEPENDS; DISCRETE RANDOM-MEDIA; OPTICAL-PROPERTIES; TURBID MEDIA; IN-VIVO; ABSORPTION; TIME; APPROXIMATION; PULSE; TRANSPORT AB Optical imaging and tomography in tissues can facilitate the quantitative study of several important chromophores and fluorophores. Several theoretical models have been validated for diffuse photon propagation in highly scattering and low-absorbing media that describe the optical appearance of tissues in the near-infrared (NIR) region. However, these models are not generally applicable to quantitative optical investigations in the visible because of the significantly higher tissue absorption in this spectral region compared with that in the NIR. We performed photon measurements through highly scattering and absorbing media for ratios of the absorption coefficient to the reduced scattering coefficient ranging approximately from zero to one. We examined experimentally the performance of the absorption-dependent diffusion coefficient defined by Aronson and Corngold [J. Opt. Soc, Am. A 16, 1066 (1999)] for quantitative estimations of photon propagation in the low- and high-absorption regimes. Through steady-state measurements we verified that the transmitted intensity is well described by the diffusion equation by considering a modified diffusion coefficient with a nonlinear dependence on the absorption. This study confirms that simple analytical solutions based on the diffusion approximation are suitable even for high-absorption regimes and shows that diffusion-approximation-based models are valid for quantitative measurements and tomographic imaging of tissues in the visible. (C) 2005 Optical Society of America. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion, Crete, Greece. Harvard Univ, Lab Bioopt & Mol Imaging,Massachusetts Gen Hosp, Ctr Mol Imaging Res, Sch Med, Charlestown, MA 02129 USA. RP Ripoll, J (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion, Crete, Greece. EM vasilis@helix.mgh.harvard.edu RI Zacharakis, Giannis/A-2544-2014; Ripoll, Jorge/J-8134-2012 OI Zacharakis, Giannis/0000-0002-6438-0773; Ripoll, Jorge/0000-0001-8856-7738 FU NIBIB NIH HHS [R01 EB 000750-1] NR 47 TC 39 Z9 39 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD MAR PY 2005 VL 22 IS 3 BP 546 EP 551 DI 10.1364/JOSAA.22.000546 PG 6 WC Optics SC Optics GA 901FX UT WOS:000227269500017 PM 15770993 ER PT J AU White, JK Agnihotri, AK Latremouille, C Messas, E Carpentier, A Torchiana, DF AF White, JK Agnihotri, AK Latremouille, C Messas, E Carpentier, A Torchiana, DF TI A method of using the pulmonary trunk Ito form a trileaflet valve SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID REPLACEMENT; WALL AB Replacement heart valves constructed from autologous tissues have been attempted, with significant variations in long-term leaflet pliability and cellular viability.(1-3) A new method of creating a potentially viable trileaflet valve from autologous pulmonary artery was investigated. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. UFR Biomed, Inst Anat, Saints Peres, France. Hop European George Pompidou, Dept Cardiovasc Surg, Paris, France. Hop European George Pompidou, Dept Cardiol, Paris, France. Hop Broussais, Dept Chirurg Cardiovasc, F-75674 Paris, France. RP White, JK (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Bullfinch 119-50 Fruit St, Boston, MA 02114 USA. EM jkwhite@partners.org NR 6 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 2005 VL 129 IS 3 BP 677 EP 679 DI 10.1016/j.jtcvs.2004.07.030 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 904AC UT WOS:000227466300031 PM 15746757 ER PT J AU Holmes, WC Foa, EB Sammel, MD AF Holmes, WC Foa, EB Sammel, MD TI Men's pathways to risky sexual behavior: Role of co-occurring childhood sexual abuse, posttraumatic stress disorder, and depression histories SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article; Proceedings Paper CT Workshop on New Dynamics of HIV Risk Among Drug-Using Men Who Have Sex With Men CY MAR 01-02, 2004 CL Bethesda, MD SP NIDA DE depression; men; posttraumatic stress disorder; sexual abuse; sexual behavior ID YOUNG-ADULTS; HIV-RISK; PREVALENCE; CHILDREN; HEALTH; ASSOCIATION; COMORBIDITY; WOMEN; TRANSMISSION; ADOLESCENTS AB Recent reports of sexually transmitted infection-rate increases among men indicate the need for renewed study of male sexual risk behavior to aid development of updated and novel risk reduction interventions. Men who have childhood sexual abuse (CSA) histories consistently report frequent sexual risk behavior. The objective of this sturdy is to explore whether posttraumatic stress disorder (PTSD) and depression are moderators and/or mediators of the association between CSA and sexual risk in adult men. A cross-sectional survey study employing random digit dial recruitment was administered to men aged 18-49 years from Philadelphia County. Two hundred ninety eight men were recruited and screened for CSA history, administered items from the Posttraumatic Stress Diagnostic Scale (PDS) and Center for Epidemiologic Studies-Depression (CES-D), and asked to estimate their number of lifetime sexual partners (LSPs). Effects of sociodemograpbic characteristics, CSA, PTSD, and depression on the number of LSPs were modeled using Poisson regression. Results show that 197 (66%) men participated; 43 (22%) had CSA histories. CSA was significantly associated with PTSD/depression (P = .03). Four sociodemographic variables (age, race, sexual identity, and education), CSA (incidence rate ratio, IRR = 1.47, P <.001), PTSD (IRR = 1.19, P = .04), depression (IRR = 1.2 9, P = .001), all 2-way interactions, and the 3-way CSA/PTSD/depression interaction (IRR = 11.00, P < .001) were associated with the number of LSPs (R-2 = 0.27). In conclusion, sexual partnership patterns unique to men with CSA histories and comorbid PTSD/depression appear to lead to substantially higher numbers of LSPs. Estimates of this relationship may have been biased toward the null by underreporting that can occur with phone surveys. Cross-sectional studies do not support causal inferences; however, the identification of a moderating and mediating influence of PTSD/depression on the relationship between CSA and sexual risk behavior is important and suggests the need for future studies with larger samples that examine trajectories for CSA, psychiatric illness, and sexual partnerships. C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Ctr Treatment & Study Anxiety, Philadelphia, PA USA. RP Holmes, WC (reprint author), Univ Penn, Sch Med, MSCE, 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM holmeswc@mail.med.upenn.edu FU NIAAA NIH HHS [AA012428]; NIDA NIH HHS [DA015635]; NIMH NIH HHS [MH62003] NR 46 TC 21 Z9 21 U1 4 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAR PY 2005 VL 82 IS 1 SU 1 BP I89 EP I99 DI 10.1093/jurban/jti028 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 911OM UT WOS:000228013900011 PM 15738316 ER PT J AU McDougal, WS AF McDougal, WS TI Preemptive lymphadenectomy markedly improves survival in patients with cancer of the penis who harbor occult metastases SO JOURNAL OF UROLOGY LA English DT Editorial Material ID CARCINOMA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2005 VL 173 IS 3 BP 681 EP 681 DI 10.1097/01.ju.0000153484.07200.f6 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 898KK UT WOS:000227075500004 PM 15711242 ER PT J AU Horwitz, EM Thames, HD Kuban, DA Levy, LB Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Hanks, GE Zietman, AL AF Horwitz, EM Thames, HD Kuban, DA Levy, LB Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Hanks, GE Zietman, AL TI Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: A multi-institutional pooled analysis SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen ID RADICAL PROSTATECTOMY; THERAPEUTIC RADIOLOGY; AMERICAN SOCIETY; ANTIGEN ERA; FOLLOW-UP; RADIOTHERAPY; IRRADIATION AB Purpose: Pooled data on 4,839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions have previously provided long-term biochemical failure (BF) and clinical outcomes using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. In this report we determined the sensitivity and specificity of several BF definitions using distant failure (DF) alone or clinical failure (CF), defined as local failure (LF) and/or DF. Materials and Methods: The pooled cohort was treated between 1986 and 1995 with external beam RT (60 Gy or greater) without pre-RT androgen suppression or planned post-RT adjuvant androgen suppression. Median followup was 6.3 years. The sensitivity and specificity of 102 definitions of BF relative to DF and LF were assessed. Results: The BF definitions with higher sensitivity and specificity than the ASTRO definition for DF only and CF are reported. The sensitivity and specificity of the ASTRO definition to predict DF alone was 55% and 68%, respectively. Three definitions had higher sensitivity and specificity, namely prostate specific antigen (PSA) greater than current nadir (lowest PSA prior to current measurement) plus 3 ng/ml (sensitivity 76% and specificity 72%), dated at the call (failure date as the date when the criterion was met), PSA greater than absolute nadir plus 2 ng/ml (sensitivity 72% and specificity 70%, dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 69% and specificity 73%). The sensitivity and specificity of the ASTRO definition to predict CF was 60% and 72%, respectively. Three definitions had higher sensitivity and specificity, namely PSA greater than current nadir plus 3 ng/ml (sensitivity 66% and specificity 77%), dated at the call, PSA greater than absolute nadir plus 2 ng/ml (sensitivity 64% and specificity 74%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 67% and specificity 78%). Conclusions: Using what is to our knowledge the largest data set of patients with prostate cancer treated with RT alone we correlated multiple definitions of BF with the strict clinical end points of DF alone and CF (DF or local failure). Defining BF as PSA greater than absolute nadir plus 2 ng/ml, dated at the call, PSA greater than current nadir plus 3 ng/ml, dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated, had higher sensitivity and specificity for DF alone or CF compared with the ASTRO definition. This information should contribute to the discussion regarding suggested modifications to the ASTRO definition of biochemical failure. C1 Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO USA. Mayo Clin, Coll Med, Div Radiat Oncol, Rochester, MN USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Horwitz, EM (reprint author), Fox Chase Canc Ctr, Dept Radiat Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM eric.horwitz@fccc.edu NR 18 TC 79 Z9 82 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2005 VL 173 IS 3 BP 797 EP 802 DI 10.1097/01.ju.0000152556.53602.64 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 898KK UT WOS:000227075500033 PM 15711272 ER PT J AU Litwin, MS Saigal, CS Yano, EM Avila, C Geschwind, SA Hanley, JM Joyce, GF Madison, R Pace, J Polich, SM Wang, MM AF Litwin, MS Saigal, CS Yano, EM Avila, C Geschwind, SA Hanley, JM Joyce, GF Madison, R Pace, J Polich, SM Wang, MM CA Urologic diseases in America TI Urologic Diseases in America project: Analytical methods and principal findings SO JOURNAL OF UROLOGY LA English DT Article DE urologic diseases; healthcare common procedure system; diagnosis AB Purpose: The burden of urological diseases on the American public is immense in human and financial terms but it has been under studied. We undertook a project, Urologic Diseases in America, to quantify the burden of urological diseases on the American public. Materials and Methods: We identified public and private data sources that contain population based data on resource utilization by patients with benign and malignant urological conditions. Sources included the Centers for Medicare and Medicaid Services, National Center for Health Statistics, Medical Expenditure Panel Survey, National Health and Nutrition Examination Survey, Department of Veterans Affairs, National Association of Children's Hospitals and Related Institutions, and private data sets maintained by MarketScan Health and Productivity Management (MarketScan, Chichester, United Kingdom), Ingenix (Ingenix, Salt Lake City, Utah) and Center for Health Care Policy and Evaluation. Using diagnosis and procedure codes we described trends in the utilization of urological services. Results: In 2000 urinary tract infections accounted for more than 6.8 million office visits and 1.3 million emergency room visits, and 245,000 hospitalizations in women with an annual cost of more than $2.4 billion. Urinary tract infections accounted for more than 1.4 million office visits, 424,000 emergency room visits and 121,000 hospitalizations in men with an annual cost of more than $1 billion. Benign prostatic hyperplasia was the primary diagnosis in more than 4.4 million office visits, 117,000 emergency room visits and 105,000 hospitalizations, accounting for $1.1 billion in expenditures that year. Urolithiasis was the primary diagnosis for almost 2 million office visits, more than 600,000 emergency room visits, and more than 177,000 hospitalizations, totaling more than $2 billion in annual expenditures. Urinary incontinence in women was the primary cause for more than 1.1 million office visits in 2000 and $452 million in aggregate primary cause for more than 1.1 million office visits in 2000 and $452 million in aggregate annual expenditures. Other manuscripts in this series present further detail for specific urologic conditions. Conclusions: Recent trends in epidemiology, practice patterns, resource utilization and costs for urological diseases have broad implications for quality of health care, access to care and the equitable allocation of scarce resources for clinical care and research. C1 Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med & Sch, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Hlth Serv, Sch Publ Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Hlth Serv Res & Dev Ctr Excellence, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND HLTH, Santa Monica, CA USA. RP Litwin, MS (reprint author), Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med & Sch, Box 951738, Los Angeles, CA 90095 USA. EM mlitwin@mednet.ucla.edu NR 7 TC 120 Z9 121 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2005 VL 173 IS 3 BP 933 EP 937 DI 10.1097/01.ju.0000152365.43125.3b PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 898KK UT WOS:000227075500057 PM 15711342 ER PT J AU Montgomery, ML Harisinghani, MG Norbash, AM Gervais, DA Kaufman, JA Mueller, PR AF Montgomery, ML Harisinghani, MG Norbash, AM Gervais, DA Kaufman, JA Mueller, PR TI CT and fluoroscopically guided percutaneous, embolization treatment of a pseudoaneurysm associated with pancreatitis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ARTERY PSEUDOANEURYSM; COIL EMBOLIZATION; PERIGRAFT LEAKS; ANEURYSMS; LESIONS; BIOPSY AB A novel approach to embolization treatment with a cyanoacrylate solution for a bleeding pseudoaneurysm associated with pancreatitis is described in the setting of a critically ill patient. Computed tomography and a C-arm fluoroscopic unit were used to guide percutaneous placement of a needle and injection of the embolic material. This technique represents an alternative form of embolization when traditional angiographic techniques are not possible. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Texas A&M Univ, Hlth Sci Ctr, Scott Sherwood & Brindley Fdn, Scott & White Mem Hosp & Clin,Dept Radiol, Temple, TX USA. RP Montgomery, ML (reprint author), Scott & White Mem Hosp & Clin, Dept Radiol, 2401 S 31st St, Temple, TX 76508 USA. EM mmontgomery@swmail.sw.org OI Norbash, Alexander/0000-0003-2986-2563 NR 20 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2005 VL 16 IS 3 BP 411 EP 415 DI 10.1097/01.RVI.0000147072.12096.3D PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 907VE UT WOS:000227745300016 PM 15758141 ER PT J AU Hua, HT Cambria, RP Chuang, SK Stoner, MC Kwolek, CJ Rowell, KS Khuri, SF Henderson, WG Brewster, DC Abbott, WM AF Hua, HT Cambria, RP Chuang, SK Stoner, MC Kwolek, CJ Rowell, KS Khuri, SF Henderson, WG Brewster, DC Abbott, WM TI Early outcomes of endovascular versus open abdominal aortic aneurysm repair in the National Surgical Quality Improvement Program-Private Sector (NSQIP-PS) SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 17-19, 2004 CL Whitefield, NH SP New England Soc Vasc Surg ID OF-VETERANS-AFFAIRS; STENT-GRAFT; STATEWIDE EXPERIENCE; CLINICAL-TRIAL; UNITED-STATES; MORTALITY; SURGERY; MIDTERM; COMPLICATIONS; DURABILITY AB Background: There remains no consensus on the appropriate application of endovascular abdominal aortic aneurysm repair (EVAR). Information from administrative databases, industry-sponsored trials, and single institutions has inherent deficiencies. This study was designed to compare early outcomes of open (OPEN) versus EVAR in a contemporary (2000 to 2003) large, multicenter prospective cohort. Methods. Fourteen academic medical centers contributed data to the National Surgical Quality Improvement Program-Private Sector (NSQIP-PS), which ensures uniform, comprehensive, prospective, and previously validated data entry by trained, independent nurse reviewers. A battery of clinical and demographic features was assessed with multivariate analysis for association with the principal study end points of 30-day operative mortality and morbidity. Results. One thousand forty-two patients underwent elective infrarenal abdominal aortic aneurysm (AAA) repairs: 460 EVAR and 582 OPEN. EVAR patients were older (74 vs 71 years, P < .0001), included more men (84.6% vs 79.6%, P < .05), and had a higher incidence of chronic obstructive pulmonary disease (25.4% vs 17.9%, P < .01). EVAR resulted in significantly reduced overall morbidity (24% vs 35%, P < .0001) and hospital stay (4 vs 9 days, P < .0001). Cardiopulmonary and renal function-related comorbidities had the expected significant impact on mortality for both procedures at univariate analysis (P < .05). While crude mortality rates between EVAR and OPEN did not differ significantly (2.8% vs 4.0%) (P = 0.32). After multivariate analysis, correlates of operative mortality included OPEN (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.03 to 5.78; P < .05), advanced age (OF, 1.11; P < .001), history of angina (OR, 5.54; P < .01), poor functional status (OR, 5.78; P < .001), history of weight loss (OR, 7.42; P < .01), and preoperative dialysis (OF, 51.4; P < .0001). EVAR also compared favorably to OPEN (OR, 2.14; 95% CI, 1.58 to 2.89; P < .0001) for overall morbidity. Conclusion: Significant morbidity accompanies AAA repair, even at major academic medical centers. These data strongly endorse EVAR as the preferred approach in the presence of significant cardiopulmonary or renal comorbidities, or poor preoperative functional status. C1 Harvard Univ, Div Vasc & Endovasc Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Ctr Clin Effectiveness Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. Univ Colorado, Hlth Outcomes Program, Boulder, CO 80309 USA. RP Hua, HT (reprint author), Harvard Univ, Div Vasc & Endovasc Surg, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM hthua@partners.org NR 39 TC 90 Z9 92 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 2005 VL 41 IS 3 BP 382 EP 389 DI 10.1016/j.jvs.2004.12.048 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 913SA UT WOS:000228172100003 PM 15838467 ER PT J AU Hoyt, CC Richardson-Burns, SM Goody, RJ Robinson, BA DeBiasi, RL Tyler, KL AF Hoyt, CC Richardson-Burns, SM Goody, RJ Robinson, BA DeBiasi, RL Tyler, KL TI Nonstructural protein sigma 1s is a determinant of reovirus virulence and influences the kinetics and severity of apoptosis induction in the heart and central nervous system SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CYCLE REGULATION; SIALIC-ACID; TRANSLATION PRODUCTS; NEURONAL APOPTOSIS; MOLECULAR-BASIS; S1 GENES; INHIBITION; PROTEIN; INJURY; IDENTIFICATION AB The mechanisms by which viruses kill susceptible cells in target organs and ultimately produce disease in the infected host remain poorly understood. Dependent upon the site of inoculation and strain of virus, experimental infection of neonatal mice with reoviruses can induce fatal encephalitis or myocarditis. Reovirus-induced apoptosis is a major mechanism of tissue injury, leading to disease development in both the brain and heart. In cultured cells, differences in the capacity of reovirus strains to induce apoptosis are determined by the S1 gene segment, which also plays a major role as a determinant of viral pathogenesis in both the heart and the central nervous system (CNS) in vivo. The S1 gene is bicistronic, encoding both the viral attachment protein sigma-1 and the nonstructural protein sigma-1-small (sigma1s). Although sigma1s is dispensable for viral replication in vitro, we wished to investigate the expression of sigma1s in the infected heart and brain and its potential role in reovirus pathogenesis in vivo. Two-day-old mice were inoculated intramuscularly or intracerebrally with either sigma1s(-) or sigma1s(+) reovirus strains. While viral replication in target organs did not differ between sigma1s(-) and sigma1s(+) viral strains, virus-induced caspase-3 activation and resultant histological tissue injury in both the heart and brain were significantly reduced in sigma1s(-) reovirus-infected animals. These results demonstrate that sigma1s is a determinant of the magnitude and extent of reovirus-induced apoptosis in both the heart and CNS and thereby contributes to reovirus pathogenesis and virulence. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Program Neurosci, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, B-182,4200 E 9th Ave, Denver, CO 80262 USA. EM Ken.Tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [R01 NS050138-04, 1R01NS50138, R01 NS050138, R01 NS051403, R01 NS051403-03] NR 38 TC 22 Z9 24 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2005 VL 79 IS 5 BP 2743 EP 2753 DI 10.1128/JVI.79.5.2743-2753.2005 PG 11 WC Virology SC Virology GA 898TF UT WOS:000227098400010 PM 15708993 ER PT J AU Stremlau, M Perron, M Welikala, S Sodroski, J AF Stremlau, M Perron, M Welikala, S Sodroski, J TI Species-specific variation in the B30.2(SPRY) domain of TRIM5 alpha determines the potency of human immunodeficiency virus restriction SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE TRANSCRIPTION; RETROVIRUS RESTRICTION; B30.2-LIKE DOMAIN; MONKEY CELLS; SIMIAN CELLS; HIV-1; PROTEIN; REPLICATION; REF1; INFECTION AB Retroviruses encounter dominant postentry restrictions in cells of particular species. Human immunodeficiency virus type 1 (HIV-1) is blocked in the cells of Old World monkeys by TRIM5alpha, a tripartite motif (TRIM) protein composed of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. Rhesus monkey TRIM5alpha (TRIM50alpha(rh)) more potently blocks HIV-1 infection than human TRIM5alpha (TRIM5alpha(hu)). Here, by studying chimeric TRIM5alpha proteins, we demonstrate that the major determinant of anti-HIV-1 potency is the B30.2(SPRY) domain. Analysis of species-specific variation in TRIM5alpha has identified three variable regions (v1, v2, and v3) within the B30.2 domain. The TRIM5alpha proteins of Old World primates exhibit expansion, duplication, and residue variation specifically in the v1 region. Replacement of three amino acids in the N terminus of the TRIM5alpha(hu) B30.2 v1 region with the corresponding TRIM5alpha(rh) residues resulted in a TRIN15alpha molecule that restricted HIV-1 nearly as efficiently as wild-type TRIM5alpha(rh) Surprisingly, a single-amino-acid change in this region of TRIM5alpha(hu), allowed potent restriction of simian immunodeficiency virus, a phenotype not observed for either wild-type TRIM5alpha(hu) or TRIM5alpha(rh). Some of the chimeric TRIM5alpha proteins that are >98% identical to the human protein yet mediate a strong restriction of HIV-1 infection may have therapeutic utility. These observations implicate the v1 variable region of the B30.2(SPRY) domain in TRIM5alpha(rh) antiviral potency. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Div AIDS,Dept Pathol,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Div AIDS,Dept Pathol,Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NHLBI NIH HHS [HL54785, P50 HL054785]; NIAID NIH HHS [P30 AI028691, P30 AI28691] NR 38 TC 269 Z9 277 U1 0 U2 10 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 MAR PY 2005 VL 79 IS 5 BP 3139 EP 3145 DI 10.1128/JVI.79.5.3139-3145.2005 PG 7 WC Virology SC Virology GA 898TF UT WOS:000227098400050 PM 15709033 ER PT J AU Yang, XZ Kurteva, S Lee, S Sodroski, J AF Yang, XZ Kurteva, S Lee, S Sodroski, J TI Stoichiometry of antibody neutralization of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; GP120 ENVELOPE GLYCOPROTEIN; INFLUENZA-VIRUS; HEMAGGLUTININ TRIMERS; MEMBRANE-FUSION; HIV TYPE-1; NONNEUTRALIZING ANTIBODIES; REPLICATION-COMPETENT; VARIABLE REGIONS; RHESUS-MONKEYS AB The human immunodeficiency virus envelope glycoproteins function as trimers on the viral surface, where they are targeted by neutralizing antibodies. Different monoclonal antibodies neutralize human immunodeficiency virus type 1 (HIV-1) infectivity by binding to structurally and functionally distinct moieties on the envelope glycoprotein trimer. By measuring antibody neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins, we demonstrate that the HIV-1 envelope glycoprotein trimer is inactivated by the binding of a single antibody molecule. Virus neutralization requires essentially all of the functional trimers to be occupied by at least one antibody. This model applies to antibodies differing in neutralizing potency and to virus isolates with various neutralization sensitivities. Understanding these requirements for HIV-1 neutralization by antibodies will assist in establishing goals for an effective AIDS vaccine. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Yang, XZ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB-609,44 Binney St, Boston, MA 02115 USA. EM Xinzhen_Yang@dfci.harvard.edu FU NIAID NIH HHS [U01 AI046725, AI46725, R01 AI031783, R37 AI024755, AI31783, AI24755] NR 86 TC 82 Z9 83 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2005 VL 79 IS 6 BP 3500 EP 3508 DI 10.1128/JVI.79.6.3500-3508.2005 PG 9 WC Virology SC Virology GA 902OR UT WOS:000227366900027 PM 15731244 ER PT J AU Fonda, SJ Bertrand, R O'Donnell, A Longcope, C McKinlay, JB AF Fonda, SJ Bertrand, R O'Donnell, A Longcope, C McKinlay, JB TI Age, hormones, and cognitive functioning among middle-aged and elderly men: Cross-sectional evidence from the Massachusetts male aging study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 9th Cognitive Aging Conference CY APR, 2002 CL ATLANTA, GA ID ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; OLDER MEN; DEHYDROEPIANDROSTERONE-SULFATE; POSTMENOPAUSAL WOMEN; SEX-HORMONES; BIOAVAILABLE TESTOSTERONE; VERBAL MEMORY; CORTISOL; PERFORMANCE AB Background. This study examines interrelationships among age, hormones, and cognition for middle-aged and elderly men, and tests whether hormones predict lower cognitive functioning and mediate the age-cognition relationship. Methods. We analyzed Time 2 data from the Massachusetts Male Aging Study, a population-based cohort study. Selection criteria included complete information on cognition and hormones (n = 981). Cognitive measures included working memory (Backward Digit Span test), speed/attention (Digit Symbol Substitution test), and spatial ability (Figural Relations test). Hormones included free testosterone, total testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstanediol glucuronide (3 α-A-diol-gluc), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (alternatively known as a "binding protein") (SHBG), prolactin (PRL), estrone (E-1), and cortisol (CRT). Age was measured in years. Adjusted analyses added educational attainment, health conditions and behaviors, body mass index, and depression. Results. Older age was associated with lower cognitive functioning. In unadjusted models, logged free and total testosterone, DHEA, and DHEAS related to higher functioning in at least one cognitive domain: logged FSH, SHBG, and LH related to lower functioning in at least one cognitive domain, and logged El, CRT, and PRL were not significant. In adjusted models, logged hormones did not relate to cognitive function except for logged E, and CRT, which had negative effects. Logged hormones did not mediate the age-cognition relationship. Conclusions. The direct effects of hormones on cognition are not significant when salient factors are considered. Further, hormones do not mediate the age-cognition relationships it is necessary to took to other explanatory pathways. C1 New England Res Inst, Watertown, MA 02472 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Boston Univ, Coll Med, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01605 USA. RP McKinlay, JB (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM stephanie.fonda@joslin.harvard.edu; JohnM@neri.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIDDK NIH HHS [DK-44995] NR 39 TC 70 Z9 73 U1 0 U2 8 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2005 VL 60 IS 3 BP 385 EP 390 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923AL UT WOS:000228880900020 PM 15860479 ER PT J AU Lansang, MC Stevanovic, R Price, DA Laffel, LMB Hollenberg, NK AF Lansang, MC Stevanovic, R Price, DA Laffel, LMB Hollenberg, NK TI ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus SO KIDNEY INTERNATIONAL LA English DT Article DE diabetes mellitus; renal hemodynamics; renin-angiotensin system; chymase ID RENIN-ANGIOTENSIN SYSTEM; ENZYME GENE POLYMORPHISM; CONVERTING-ENZYME; HEALTHY HUMANS; II GENERATION; NEPHROPATHY; HYPERGLYCEMIA; COMPLICATIONS; HYPERTENSION; ASSOCIATION AB Background. The enormous contribution of renin-angiotensin system (RAS) interruption with ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers (ARB) in the treatment of diabetic nephropathy has led to interest in the factors involved in angiotensin II (Ang II) generation. In normal subjects, RAS interruption using an ARB produced a 50% greater renal plasma flow (RPF) rise than with an ACE inhibitor, suggesting a substantial contribution of non-ACE pathways. Moreover, immunohistochemistry studies in kidneys of overtly proteinuric diabetic subjects showed up-regulation of chymase, an alternative Ang II-generating enzyme. Our aim was to determine the degree to which the non-ACE pathways contribute to RAS activation in type 1 diabetes mellitus (DM). Methods. Type 1 DM patients (N = 37,14 M/23 F; age 31 +/- 2 years; DM duration 16 +/- 1.7 years; HbAlc 7.7.0 +/- 0.3%) were studied on a high-salt diet. They received captopril 25 mg po one day and candesartan 16 mg po the next day. RPF and glomerular filtration rate (GFR) were measured before and up to 4 hours after drug administration. Results. Both captopril and candesartan induced a significant rise in RPF (baseline vs. peak <0.0001 for both), and the rise was concordant for the 2 drugs (r = 0.77, P < 0.001). However, the RPF responses were not significantly different between the 2 drugs (captopril 72 +/- 11 mL/min/1.73m(2), candesartan 75 +/- 12, P = 0.841). Conclusion. In predominantly normoalbuminuric, normotensive type 1 DM, activation of the intrarenal RAS reflects a mechanism involving primarily the classic ACE pathway. C1 Univ Florida, Div Endocrinol, Dept Med, Gainesville, FL 32610 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. RP Lansang, MC (reprint author), Univ Florida, Div Endocrinol, Dept Med, POB 100226, Gainesville, FL 32610 USA. EM lansamc@medicine.ufl.edu FU NCRR NIH HHS [M01RR026376]; NHLBI NIH HHS [T32 HL-07609]; NIDDK NIH HHS [1 R01 DK54668-01]; PHS HHS [P01AC00059916, 1P50 ML 53000-01] NR 26 TC 10 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2005 VL 67 IS 3 BP 1033 EP 1037 DI 10.1111/j.1523-1755.2005.00167.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 897OC UT WOS:000227013500023 PM 15698442 ER PT J AU Henson, JW Gaviani, P Gonzalez, RG AF Henson, JW Gaviani, P Gonzalez, RG TI MRI in treatment of adult gliomas SO LANCET ONCOLOGY LA English DT Review ID GROWTH-FACTOR-RECEPTOR; HIGH-GRADE GLIOMAS; MAGNETIC-RESONANCE-SPECTROSCOPY; CONTRAST-ENHANCED MR; BRAIN-TUMORS; GLIOBLASTOMA-MULTIFORME; SECONDARY GLIOBLASTOMAS; RESPONSE CRITERIA; MALIGNANT GLIOMA; DE-NOVO AB Diffuse astrocytomas of the adult cerebral hemispheres are unique among tumours in human beings in the extent to which their imaging features are related to histopathological characteristics and clinical behaviour. However, understanding is still restricted about the value of imaging features in the measurement of response and of progression in these tumours. The present approach used in clinical trials, which consists of an anatomical measurement of the enhancing tumour on MRI, has many problems, and might not be acceptable as a surrogate endpoint for survival in patients with glioblastoma who are enrolled in clinical trials. Dynamic imaging techniques, such as capillary permeability mapping, are being used in studies of new drugs that target specific molecular features of gliomas; however, the validity of these techniques has not been elucidated. Diffusion imaging can be valuable for fibre-tract mapping to assist surgical planning and might become useful in measuring early response to treatment in densely cellular tumours. Functional imaging techniques can be used to localise motor, sensory, and language-control areas before surgery. Intraoperative MRI has produced improvements in the extent of tumour resection, and molecular imaging is another technique on the horizon, which could come to have a role in clinical trials in the near future. Thus, as a rapidly expanding sphere of investigation, brain-tumour imaging is producing great excitement. The aim of these new techniques is to aid the identification of more effective treatments. C1 Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Steven E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 40 TC 59 Z9 64 U1 0 U2 5 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2005 VL 6 IS 3 BP 167 EP 175 DI 10.1016/S1470-2045(05)01767-5 PG 9 WC Oncology SC Oncology GA 905OK UT WOS:000227578000019 PM 15737833 ER PT J AU Zirkle, M Blum, R Raemer, DB Healy, G Roberson, DW AF Zirkle, M Blum, R Raemer, DB Healy, G Roberson, DW TI Teaching emergency airway management using medical simulation: A pilot program SO LARYNGOSCOPE LA English DT Article DE airway; crisis resource management; medical education stimulation. ID SKILLS; AVIATION; ERROR; CARE AB Objective: Simulation is a tool that has been used successfully in many high performance fields to permit training in rare and hazardous events. Our goal was to develop and evaluate a program to teach airway crisis management to otolaryngology trainees using medical simulation. Methods: A full-day curriculum in the management of airway emergencies was developed. The program consists of three airway emergency scenarios, developed in collaboration between attending otolaryngologists and faculty from the Center for Medical Simulation. Following each scenario, the participants are led in a structured, video-assisted debriefing by a trained debriefer. Didactic material on team leadership and crisis management is built into the debriefings. Pediatric otolaryngology fellows, residents, and medical students have participated in the four courses that have been held to date. Participants evaluated the program on a five-point Likert scale. Results. A total of 17 trainees participated in four pilot training courses. The survey data are as follows: overall program, 5.0 (SD, 0.00); course goals, 4.79 (SD, 0.43); realism, 4.36 (SD, 0.63); value of lecture, 4.71 (SD, 0.47); and quality of debriefings, 4.92 (SD, 0.28). Sample comments include: "This is a valuable tool for students and residents since true emergencies in ORL are often lifethreatening and infrequent," and "This is a great course-really all physicians should experience it." Overall evaluation was extremely positive and both residents and fellows described the course as filling an important void in their education. Conclusion: Medical simulation can be an extremely effective method for teaching airway crisis management and teamwork skills to otolaryngology trainees at all levels. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. Childrens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Harvard Ctr Med Simulat, Boston, MA 02115 USA. RP Zirkle, M (reprint author), Toronto Gen Hosp, Eaton N 7-242,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. NR 16 TC 16 Z9 17 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2005 VL 115 IS 3 BP 495 EP 500 DI 10.1097/01.mlg.0000157834.69121.b1 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 906KA UT WOS:000227638400020 PM 15744165 ER PT J AU Mikulec, AA Poe, DS McKenna, MJ AF Mikulec, AA Poe, DS McKenna, MJ TI Operative management of superior semicircular canal dehiscence SO LARYNGOSCOPE LA English DT Article DE hearing loss; Hennebert's; superior semicircular canal dehiscence; Tullio phenomenon; vertigo ID PRESSURE-INDUCED VERTIGO; CONDUCTIVE HEARING-LOSS; BONE DEHISCENCE AB Objective: To assess the outcomes of patients undergoing surgical management of superior semicircular canal dehiscence (SSCD). Study Design: Retrospective review. Methods: The medical records of all patients undergoing surgical treatment for SSCD at our institution between 2000 and 2004 were reviewed. Results: Eleven patients underwent unilateral operative management via a middle fossa approach. Ten patients were treated successfully by canal plugging and one unsuccessfully by canal re-roofing. Plugging of SSCD provided resolution of sound- and pressure-induced nystagmus, autophony, and conductive hearing loss (HL). One patient experienced a mild high-frequency sensorineural HL and two patients experienced both a mild high-frequency sensorineural HL and a reduction in vestibular function. Two additional patients underwent exploration for SSCD but were found to have a thin layer of bone overlying the canal. Conclusions: Plugging of the SSCD, while efficacious in alleviating the symptoms of the disease, may cause loss of labyrinthine function beyond the superior canal. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Childrens Hosp, Dept Otolaryngol & Commun Disorders, Boston, MA 02115 USA. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 62 Z9 66 U1 0 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 MAR PY 2005 VL 115 IS 3 BP 501 EP 507 DI 10.1097/01.mlg.0000157844.48036.e7 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 906KA UT WOS:000227638400021 PM 15744166 ER PT J AU Salomatina, E Neel, V Anderson, RR Yaroslavsky, AN AF Salomatina, E Neel, V Anderson, RR Yaroslavsky, AN TI Imaging of tetracycline fluorescence polarization for discriminating nonmelanoma skin tumors from healthy tissue SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 8 BP 4 EP 4 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000009 ER PT J AU Laubach, HJ Childs, JJ Smirnov, M Altshuler, GB Anderson, RR Manstein, D AF Laubach, HJ Childs, JJ Smirnov, M Altshuler, GB Anderson, RR Manstein, D TI Photothermal treatment of the dermis with a broad-spectrum near-infrared light source SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Palomar Med Technol, Burlington, MA 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 18 BP 7 EP 7 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000019 ER PT J AU Echague, AV Kamagaya, Y Akita, H Farinelli, W Gallagher, J Redmond, RW Kochevar, IE Anderson, RR AF Echague, AV Kamagaya, Y Akita, H Farinelli, W Gallagher, J Redmond, RW Kochevar, IE Anderson, RR TI Photochemical tissue bonding for closure of incision and excision wounds in pig skin SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellcome Ctr Photomed, Boston, MA 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 35 BP 12 EP 12 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000035 ER PT J AU Sarasombath, PA Rius, F Anderson, RR Manstein, D AF Sarasombath, PA Rius, F Anderson, RR Manstein, D TI Quantitative sensory testing for 810 nm diode laser exposure of all skin types SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 85 BP 28 EP 28 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000081 ER PT J AU Kossida, T Farinelli, WA Flotte, T Anderson, RR AF Kossida, T Farinelli, WA Flotte, T Anderson, RR TI A novel approach for removal of skin tattoos with long microsecond-domain laser pulses SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 89 BP 29 EP 29 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000085 ER PT J AU Tannous, Z Laubach, HJ Anderson, RR Manstein, D AF Tannous, Z Laubach, HJ Anderson, RR Manstein, D TI Changes of epidermal pigment distribution after fractional resurfacing: A clinicopathologic correlation SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 98 BP 32 EP 32 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000095 ER PT J AU Astner, S Wolmers, SK Tsao, SS AF Astner, S Wolmers, SK Tsao, SS TI Increased efficacy in treatment of facial telangiectasia and rosacea utilizing Starlux (TM) IPL technology with variable pulsewidth and fluence SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Wellman Ctr Photomed, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 105 BP 35 EP 35 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000102 ER PT J AU Astner, S Anderson, RR Tsao, SS AF Astner, S Anderson, RR Tsao, SS TI Clinical use of a 1450 nm diode laser for long-term acne control SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 110 BP 36 EP 36 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000107 ER PT J AU Strasswimmer, J Grande, DJ AF Strasswimmer, J Grande, DJ TI Laser activation of photodynamic therapy: A placebo-controlled dose-response study SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02215 USA. Myst Valley Dermatol, Medford, MA 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 203 BP 62 EP 62 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000189 ER PT J AU Strasswimmer, J Pierce, MC Park, H Kuwahara, T de Boer, JF Anderson, RR AF Strasswimmer, J Pierce, MC Park, H Kuwahara, T de Boer, JF Anderson, RR TI Optical biopsy and treatment of severe actinic cheilitis SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Myst Valley Dermatol, Medford, MA USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 206 BP 63 EP 63 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000192 ER PT J AU Laubach, HJ Tannous, Z Anderson, RR Manstein, D AF Laubach, HJ Tannous, Z Anderson, RR Manstein, D TI A histological evaluation of the dermal effects after fractional photothermolysis treatment SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 288 BP 86 EP 86 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000259 ER PT J AU Salomatina, E Anderson, RR Yaroslavsky, AN AF Salomatina, E Anderson, RR Yaroslavsky, AN TI Optical properties of normal and cancerous human skin in the visible and near infrared spectral range SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 311 BP 94 EP 94 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000282 ER PT J AU Dutcher, JP Lee, S Gallagher, RE Makary, AZ Hines, JD Londer, H Farnen, JP Bennett, JM Paietta, E Rowe, JM Goloubeva, O Wiernik, PH AF Dutcher, JP Lee, S Gallagher, RE Makary, AZ Hines, JD Londer, H Farnen, JP Bennett, JM Paietta, E Rowe, JM Goloubeva, O Wiernik, PH TI Phase II study of all-trans retinoic acid in the accelerated phase or early blastic phase of chronic myeloid leukemia: A study of the Eastern Cooperative Oncology Group (E1993) SO LEUKEMIA & LYMPHOMA LA English DT Article DE all-trans retinoic acid; CML; blast crisis; accelerated phase ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; INTERFERON-ALPHA; PROGENITOR CELLS; CLINICAL-TRIALS; IN-VITRO; DIFFERENTIATION; THERAPY; CRISIS; REMISSION AB The aims of this study were to evaluate the safety and efficacy of all-trans retinoic acid ( ATRA) in the treatment of the accelerated and blastic phase of chronic myeloid leukemia (CML) and to evaluate in vitro correlates of biological activity. ATRA was administered in an intermittent schedule to patients with CML in the accelerated or blastic phases for a 6 week induction period, which was continued if there was evidence of clinical response or stable disease. If the patient was progressing at 6 weeks, interferon-alpha could be added to the ATRA. Laboratory correlative studies were performed prior to treatment and at intervals during treatment to evaluate effects on maturation and differentiation, and on CML progenitor cell growth by assessment of colony-forming cells (CFC). Eighteen patients were enrolled. There was 1 complete response, 1 partial response and 2 with hematological improvement. A fifth patient was stable on ATRA and interferon for several months. Laboratory data for the responders demonstrated high sensitivity of primary CFC to ATRA prior to treatment and low serial CFC counts on ATRA therapy. ATRA demonstrated clinical and hematological activity in 5 of 18 patients with the accelerated phase of CML, and there was evidence of a biological effect in laboratory studies of 3 of the 5 patients' progenitor cells. Combination therapy with other differentiating agents may be useful in this disease. C1 New York Med Coll, Our Lady Mercy Med Ctr, MBCCOP, Bronx, NY 10466 USA. Albert Einstein Coll NY, Bronx, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Geisinger Med Ctr, Danville, PA 17822 USA. Case Western Metrohealth Med Ctr, Cleveland, OH USA. N Mem Med Ctr, St Louis, MO USA. Gunderson Luthern, La Crosse, WI USA. Univ Rochester, Rochester, NY USA. Rambam Med Ctr, Haifa, Israel. RP New York Med Coll, Our Lady Mercy Med Ctr, MBCCOP, 600 E 233rd St, Bronx, NY 10466 USA. EM jpd4401@aol.com FU NCI NIH HHS [CA 23318, CA 11083, CA 14958, CA 66636, CA 14548, CA21115] NR 26 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 2005 VL 46 IS 3 BP 377 EP 385 DI 10.1080/10428190400013100 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 881OX UT WOS:000225878000008 PM 15621827 ER PT J AU Shechter, SM Bryce, CL Alagoz, O Kreke, JE Stahl, JE Schaefer, AJ Angus, DC Roberts, MS AF Shechter, SM Bryce, CL Alagoz, O Kreke, JE Stahl, JE Schaefer, AJ Angus, DC Roberts, MS TI A clinically based discrete-event simulation of end-stage liver disease and the organ allocation process SO MEDICAL DECISION MAKING LA English DT Article DE liver transplantation; discrete-event simulation; simulation modeling; Monte Carlo simulation; organ allocation; patient survival; graft survival; policy analysis AB Background. The optimal allocation of scarce donor livers is a contentious health care issue requiring careful analysis. The objective of this article was to design a biologically based discrete-event simulation to test proposed changes in allocation policies. Methods. The authors used data from multiple sources to simulate end-stage liver disease and the complex allocation system. To validate the model, they compared simulation output with historical data. Results. Simulation outcomes were within 1% to 2% of actual results far measures such as new candidates, donated livers, and transplants by year. The model overestimated the yearly size of the waiting list by 5% in the last year of the simulation and the total number of pretransplant deaths by 10%. Conclusion. The authors created a discrete-event simulation model that represents the biology of end-stage liver disease and the health care organization of transplantation in the United States. C1 Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Ind Engn, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med,Sect Decis Sci & Clin Syst, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, MGH Inst Technol Assessment, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA 15213 USA. RP Roberts, MS (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. RI Angus, Derek/E-9671-2012; OI Bryce, Cindy/0000-0001-6356-6675 FU AHRQ HHS [R01HS09694] NR 14 TC 46 Z9 48 U1 0 U2 3 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 MAR-APR PY 2005 VL 25 IS 2 BP 199 EP 209 DI 10.1177/0272989X04268956 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 911ON UT WOS:000228014000008 PM 15800304 ER PT J AU Ahmad, S Vlachaki, MT Teslow, TN Amosson, CM McGary, J Teh, BS Woo, SY Butler, EB Grant, WH AF Ahmad, S Vlachaki, MT Teslow, TN Amosson, CM McGary, J Teh, BS Woo, SY Butler, EB Grant, WH TI Impact of setup uncertainty in the dosimetry of prostate and surrounding tissues in prostate cancer patients treated with Peacock/IMRT SO MEDICAL DOSIMETRY LA English DT Article DE prostate cancer; IMRT; setup error ID MODULATED RADIATION-THERAPY; CONFORMAL RADIOTHERAPY; ACUTE TOXICITY; BOOST THERAPY; CARCINOMA; BLADDER; RECTUM; MOVEMENT; DELIVERY; ISSUES AB The purpose of this paper was to assess the effect of setup uncertainty on dosimetry of prostate, seminal vesicles, bladder, rectum, and colon in prostate cancer patients treated with Peacock intensity-modulated radiation therapy (IMRT). Ten patients underwent computed tomography (CT) scans using the "prostate box" for external, and an "endorectal balloon" for target immobilization devices, and treatment plans were generated (T1). A maximum of +/- 5-mm setup error was chosen to model dosimetric effects. Isodose lines from the T1 treatment plan were then superimposed on each patient's CT anatomy shifted by 5 mm toward the cephalad and caudal direction, generating 2 more dosimetric plans (H1 and H2, respectively). Average mean doses ranged from 74.5 to 74.92 Gy for prostate and 73.65 to 74.94 Gy for seminal vesicles. Average percent target volume below 70 Gy increased significantly for seminal vesicles, from 0.53% to 6.26%, but minimally for prostate, from 2.08% to 4.4%. Dose statistics adhered to prescription limits for normal tissues. Setup uncertainty had minimum impact on target dose escalation and normal tissue dosing. The impact of target dose inhomogeneity is currently evaluated in clinical studies. (C) 2005 American Association of Medical Dosimetrists. C1 Dept Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Ahmad, S (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Radiat Oncol, Everett Tower,1200 N Everett Dr,Room B603, Oklahoma City, OK 73104 USA. NR 39 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 J9 MED DOSIM JI Med. Dosim. PD SPR PY 2005 VL 30 IS 1 BP 1 EP 7 DI 10.1016/j.meddos.2004.10.001 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 018XK UT WOS:000235797900001 PM 15749004 ER PT J AU Sillanpaa, J Chang, J Mageras, G Riem, H Ford, E Todor, D Ling, CC Amols, H AF Sillanpaa, J Chang, J Mageras, G Riem, H Ford, E Todor, D Ling, CC Amols, H TI Developments in megavoltage cone beam CT with an amorphous silicon EPID: Reduction of exposure and synchronization with respiratory gating SO MEDICAL PHYSICS LA English DT Article DE electronic portal imaging device; cone beam CT; setup verfication ID FLAT-PANEL IMAGER; PORTAL IMAGING DEVICE; COMPUTED-TOMOGRAPHY; CONFORMAL RADIOTHERAPY; TREATMENT VERIFICATION; RADIATION-THERAPY; LUNG-CANCER; RECONSTRUCTION; SCANNER; FEASIBILITY AB We have studied the feasibility of a low-dose megavoltage cone beam computed tomography (MV CBCT) system for visualizing the gross tumor volume in respiratory gated radiation treatments of nonsmall-cell lung cancer. The system consists of a commercially available linear accelerator (LINAC), an amorphous silicon electronic portal imaging device, and a respiratory gating system. The gantry movement and beam delivery are controlled using dynamic beam delivery toolbox, a commercial software package for executing scripts to control the LINAC. A specially designed interface box synchronizes the LINAC, image acquisition electronics, and the respiratory gating system. Images are preprocessed to remove artifacts due to detector sag and LINAC output fluctuations. We report on the output, flatness, and symmetry of the images acquired using different imaging parameters. We also examine the quality of three-dimensional (3D) tomographic reconstruction with projection images of anthropomorphic thorax, contrast detail, and motion phantoms. The results show that, with the proper choice of imaging parameters, the flatness and symmetry are reasonably good with as low as three beam pulses per projection image. Resolution of 5% electron density differences is possible in a contrast detail phantom using 100 projections and 30 MU. Synchronization of image acquisition with simulated respiration also eliminated motion artifacts in a moving phantom, demonstrating the system's capability for imaging patients undergoing gated radiation therapy. The acquisition time is limited by the patient's respiration (only one image per breathing cycle) and is under 10 min for a scan of 100 projections. In conclusion, we have developed a MV CBCT system using commercially available components to produce 3D reconstructions, with sufficient contrast resolution for localizing a simulated lung tumor, using a dose comparable to portal imaging. (c) 2005 American Association of Physicists in Medicine. C1 Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. Varian Med Syst, Baden, Switzerland. VA Puget Sound, Seattle, WA 98108 USA. Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. RP Sillanpaa, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med Phys, 1275 York Ave, New York, NY 10021 USA. EM changj@mskcc.org RI Grams, Michael/G-5197-2011; OI Mageras, Gikas/0000-0001-9851-4306 FU NCI NIH HHS [P01-CA59017] NR 34 TC 45 Z9 46 U1 0 U2 2 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 MAR PY 2005 VL 32 IS 3 BP 819 EP 829 DI 10.1118/1.1861522 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 910DN UT WOS:000227910600020 PM 15839355 ER PT J AU Yokoyama, T Banta, S Berthiaume, F Nagrath, D Tompkins, RG Yarmush, ML AF Yokoyama, T Banta, S Berthiaume, F Nagrath, D Tompkins, RG Yarmush, ML TI Evolution of intrahepatic carbon, nitrogen, and energy metabolism in a D-galactosamine-induced rat liver failure model SO METABOLIC ENGINEERING LA English DT Article DE perfused liver; metabolic flux analysis; principal component analysis; mitochondria; amino acids ID FULMINANT HEPATIC-FAILURE; TUMOR-NECROSIS-FACTOR; KETONE-BODY RATIO; PLASMA AMINO-ACIDS; ARTERIAL BLOOD; NITRIC-OXIDE; CULTURED-HEPATOCYTES; LACTIC-ACIDOSIS; ENCEPHALOPATHY; TRANSPLANTATION AB A clearer picture of the hepatic metabolic pathways affected by fulminant hepatic failure (FHF) would help develop nutritional support and nonsurgical therapies for FHF. We characterized the evolution of hepatic metabolism in a rat model of FHF using an isolated perfused liver system together with a mass-balance model of intermediary metabolism. Principal component analysis (PCA) was used to identify potential new sensitive markers for FHF. To induce FHF, rats were given two D-galactosamine injections under fasting C:conditions. Controls were fasted only. Livers were harvested 1, 4, 8, and 12 h later and perfused with Eagle minimal essential medium supplemented with amino acids and bovine serum albumin, and equilibrated with 95% O-2/5% CO2. At the 1 h time point, lactate release increased concomitant with a decrease in gluconeogenesis, TCA cycle and mitochondrial electron transport fluxes. At 4 h, amino acid metabolism and urea cycle fluxes were significantly depressed. By 8 h, gluconeogenesis had switched to glycolysis. By 12 h, amino acid metabolism was broadly inhibited, and there was a net release of many amino acids. Mass-balance analysis shows that the main source of ATP production in the FHF liver gradually changed from mitochondrial oxidative phosphorylation to glycolysis. PCA suggests that a linear combination of glucose, lactate, and glutamine concentrations in arterial plasma is a sensitive marker for FHF. We conclude that D-galactosamine causes early mitochondrial dysfunction while glycolytic ATP synthesis remains functional. Markers that are indirectly linked to these pathways may be used to evaluate the progression of FHF. (c) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, Boston, MA 01224 USA. Shriners Hosp Children, Boston, MA 01224 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, 51 Blossom St, Boston, MA 01224 USA. EM fberthia@sbi.org OI Nagrath, Deepak/0000-0002-8999-2282 FU NIDDK NIH HHS [R01 DK43371]; NIGMS NIH HHS [R01 GM58125] NR 43 TC 27 Z9 32 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 1096-7176 J9 METAB ENG JI Metab. Eng. PD MAR PY 2005 VL 7 IS 2 BP 88 EP 103 DI 10.1016/j.ymben.2004.09.003 PG 16 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 913XY UT WOS:000228190100003 PM 15781418 ER PT J AU Brachmann, SM Ueki, K Engelman, JA Kahn, RC Cantley, LC AF Brachmann, SM Ueki, K Engelman, JA Kahn, RC Cantley, LC TI Phosphoinositide 3-kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAT ADIPOSE-CELLS; RECEPTOR SUBSTRATE-1; GLUCOSE-TRANSPORT; 1-PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; EMBRYONIC LETHALITY; SIGNALING PATHWAYS; DIABETES-MELLITUS; P85-ALPHA SUBUNIT; SKELETAL-MUSCLE AB Studies ex vivo have shown that phosphoinositide 3-kinase (PI3K) activity is necessary but not sufficient for insulin-stimulated glucose uptake. Unexpectedly, mice lacking either of the PI3K regulatory subunits p85alpha or p85beta exhibit increased insulin sensitivity. The insulin hypersensitivity is particularly unexpected in p55alpha(-/-) p55-p50alpha(-/-) mice, where a decrease in p110alpha and p110beta catalytic subunits was observed in insulin-sensitive tissues. These results raised the possibility that decreasing total PI3K available for stimulation by insulin might circumvent negative feedback loops that ultimately shut off insulin-dependent glucose uptake in vivo. Here we present results arguing against this explanation. We show that p110alpha(-/-) p110beta(-/-) mice exhibit mild glucose intolerance and hyperinsulinemia in the fasted state. Unexpectedly, p110alpha(-/-) p110beta(-/-) mice showed a similar to50% decrease in p85 expression in liver and muscle. Consistent with this in vivo observation, knockdown of p110 by RNA interference in mammalian cells resulted in loss of p85 proteins due to decreased protein stability. We propose that insulin sensitivity is regulated by a delicate balance between p85 and p110 subunits and that p85 subunits mediate a negative role in insulin signaling independent of their role as mediators of PI3K activation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct,Dept Syst Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Free Univ Berlin, Inst Biochem, D-1000 Berlin, Germany. RP Cantley, LC (reprint author), Beth Israel Hosp, NRB, Div Signal Transduct, 10th Floor 330, Boston, MA 02215 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [P01 CA089021, P01-CA89021, T32 CA009172]; NIDDK NIH HHS [DK 55545, R01 DK055545]; NIGMS NIH HHS [GM41890, R01 GM041890, R37 GM041890] NR 47 TC 97 Z9 103 U1 0 U2 6 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 MAR PY 2005 VL 25 IS 5 BP 1596 EP 1607 DI 10.1128/MCB.25.5.1596-1607.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 898OI UT WOS:000227085700003 PM 15713620 ER PT J AU Hu, W Xu, RJ Zhang, GF Jin, JF Szulc, ZM Bielawski, J Hannun, YA Obeid, LM Mao, CG AF Hu, W Xu, RJ Zhang, GF Jin, JF Szulc, ZM Bielawski, J Hannun, YA Obeid, LM Mao, CG TI Golgi fragmentation is associated with ceramide-induced cellular effects SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIN CYTOSKELETON; INDUCED APOPTOSIS; FOCAL ADHESION; CELLS; GLYCOSYLATION; FIBRONECTIN; METABOLISM; RECEPTOR; BETA-1-INTEGRINS; ORGANIZATION AB Ceramide has been shown to cause anoikis, a subtype of apoptosis due to inadequate cell adhesion. However, the underlying mechanism is unclear. Herein, we report that D-e-C-6-ceramide (D-e-Cer), via generating sphingosine, disrupts the Golgi complex (GC), which is associated with various cellular effects, including anoikis. Treatment of HeLa cells with D-e-Cer caused cell elongation, spreading inhibition, rounding, and detachment before apoptosis (anoikis). In D-e-Cer-treated cells, glycosylation of beta1 integrin in the GC was inhibited, thus its associated integrin receptors failed to translocate to the cell surface. Ceramide treatment also inhibited the reorganization of both microtubule and F-actin cytoskeletons, focal adhesions, and filopodia. These cellular effects were preceded by fragmentation of the Golgi complex. In contrast, L-e-C-6-ceramide (L-e-Cer), the enantiomer of D-e-Cer, failed to induce these cellular effects. Mass spectrometric analysis revealed that treatment HeLa cells with D-e-Cer but not L-e-Cer caused a >50-fold increase in the levels of sphingosine, a product of hydrolysis of ceramide. Treatment with D-e-sphingosine and its enantionter, L-e-sphingosine, caused massive perinuclear vacuolization, Golgi fragmentation, and cell rounding. Together, these results suggest that sphingosine generated from hydrolysis of ceramide causes the GC disruption, leading to various cellular effects. C1 Med Univ S Carolina, Dept Med & Biochem, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Mol Biol, Charleston, SC 29425 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Ralph H Johnson Vet Adm Hosp, Charleston, SC 29401 USA. RP Mao, CG (reprint author), Med Univ S Carolina, Dept Med & Biochem, Charleston, SC 29425 USA. EM maoc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [R01 CA104834, P01 CA097132]; NCRR NIH HHS [P20 RR017677, P20RR017677] NR 45 TC 53 Z9 56 U1 0 U2 0 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 MAR PY 2005 VL 16 IS 3 BP 1555 EP 1567 DI 10.1091/mbc.E04-07-0594 PG 13 WC Cell Biology SC Cell Biology GA 902SZ UT WOS:000227378100046 PM 15647381 ER PT J AU Zeng, WQ Gao, HL Gray, G Brueton, L Hutchin, T Roseann, M Shih, V AF Zeng, WQ Gao, HL Gray, G Brueton, L Hutchin, T Roseann, M Shih, V TI Partial uniparental isodisomy of chromosome one in fumarase deficiency patient. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2005) CY MAR 06-09, 2005 CL Pacific Grove, CA SP Genzyme Corp, Mead Johnson Nutr, NIDDK, NIH, Off Rare Dis, Dept Hlth & Human Serv, Ucyclyd Pharma, Actelion Pharmaceut US Inc, Abbott Labs, Ross Prod Div, SHS N Amer, Appl Biosyst, Appl Nutr Corp, BioMarin Pharmaceut Inc, Milupa N Amer, Vitaflo, Biochrom Inc, Cambrooke Foods, Hitachi High Technologies Amer Inc, Natl Urea Cycle Defects Fdn, Pickering Labs Inc, Rare Dis Therapeut Inc, Sigma Tau Pharmaceut, Transkarot Therapies Inc C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Childrens Hosp, Birmingham B16 8ET, W Midlands, England. Massachusetts Gen Hosp, Amino Acid Disorders Lab, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2005 VL 84 IS 3 BP 242 EP 242 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 906NH UT WOS:000227648400115 ER PT J AU Miguel, EC Leckman, JF Rauch, S do Rosario-Campos, MC Hounie, AG Mercadante, MT Chacon, P Pauls, DL AF Miguel, EC Leckman, JF Rauch, S do Rosario-Campos, MC Hounie, AG Mercadante, MT Chacon, P Pauls, DL TI Obsessive-compulsive disorder phenotypes: implications for genetic studies SO MOLECULAR PSYCHIATRY LA English DT Review DE obsessive-compulsive disorder; obsessive behaviors; compulsive behaviors; genetics; molecular genetics ID LA-TOURETTE-SYNDROME; PRADER-WILLI-SYNDROME; STREPTOCOCCAL INFECTIONS PANDAS; AUTOSOMAL-DOMINANT TRANSMISSION; POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN REUPTAKE INHIBITORS; BLOOD-FLOW ABNORMALITIES; CHRONIC TIC DISORDER; HOPKINS OCD FAMILY; FOLLOW-UP AB Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include ( 1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and ( 3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes. C1 Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05403010 Sao Paulo, Brazil. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurodev Genet Unit, Charlestown, MA USA. Univ Prebiteriana Mackenzie, Pervas Dev Disorder Program, Sao Paulo, Brazil. RP Miguel, EC (reprint author), Univ Sao Paulo, Sch Med, Dept Psychiat, Rua Dr Ovidio Pires de Campos,S-N, BR-05403010 Sao Paulo, Brazil. EM ecmiguel@usp.br RI Miguel, Euripedes/B-2871-2008; Chacon, Priscila/G-9401-2012; do Rosario, Maria Conceicao/E-5213-2012 OI do Rosario, Maria Conceicao/0000-0002-9687-0072 NR 178 TC 155 Z9 161 U1 6 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2005 VL 10 IS 3 BP 258 EP 275 DI 10.1038/sj.mp.4001617 PG 18 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 901QP UT WOS:000227297300008 PM 15611786 ER PT J AU Tannous, BA Kim, DE Fernandez, JL Weissleder, R Breakefield, XO AF Tannous, BA Kim, DE Fernandez, JL Weissleder, R Breakefield, XO TI Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo SO MOLECULAR THERAPY LA English DT Article ID RENILLA-RENIFORMIS LUCIFERASE; FIREFLY LUCIFERASE; BIOLUMINESCENT REPORTER; TUMORS; HYBRIDIZATION; PURIFICATION; INDICATORS; ANALOGS; CLONING; LABEL AB Photoproteins have played a major role in advancing our understanding of biological processes. A broader array of biocompatible, nontoxic, and novel reporters can serve to expand this potential. Here we describe the properties of a luciferase from the copepod marine organism Gaussia princeps. It is a monomeric protein composed of 185 aa (19.9 kDa) with a short coding sequence (555 bp) making it suitable for viral vectors. The humanized form of Gaussia luciferase (hGLuc) was efficiently expressed in mammalian cells following delivery by HSV-1 amplicon vectors. It was found to be nontoxic and naturally secreted, with flash bioluminescence characteristics similar to those of other coelenterazine luciferases. hGLuc generated over 1000-fold higher bioluminescent signal intensity from live cells together with their immediate environment and over 100-fold higher intensity from viable cells alone (not including secreted luciferase) or cell lysates, compared to humanized forms of firefly (hFLuc) and Renilla (hRLuc) luciferases expressed under similar conditions. Furthermore, hGLuc showed 200-fold higher signal intensity than hRLuc and intensity comparable to that of hFLuc in vivo under standard imaging conditions. Gaussia luciferase provides a sensitive means of imaging gene delivery and other events in living cells in culture and in vivo, with a unique combination of features including high signal intensity, secretion, and ATP independence, thus being able to report from the cells and their environment in real time. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp East, Mol Neurogenet Unit, Bldg 149,13th St,Room 6101, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU NCI NIH HHS [CA92782, CA69246, CA86355] NR 34 TC 368 Z9 387 U1 1 U2 37 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2005 VL 11 IS 3 BP 435 EP 443 DI 10.1016/j.ymthe.2004.10.016 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 906EL UT WOS:000227623200015 PM 15727940 ER PT J AU Hogarth, P Kayson, E Kieburtz, K Marder, K Oakes, D Rosas, D Shoulson, I Wexler, NS Young, AB Zhao, HW AF Hogarth, P Kayson, E Kieburtz, K Marder, K Oakes, D Rosas, D Shoulson, I Wexler, NS Young, AB Zhao, HW CA US Venezuela Huntington Dis Res Gr Huntington study Grp TI Interrater agreement in the assessment of motor manifestations of Huntington's disease SO MOVEMENT DISORDERS LA English DT Article DE Huntington's disease; clinical trials; disease progression ID RILUZOLE; VENEZUELA; HD AB With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States-Venezuela Collaborative HD Research Project. Observers were asked to rate a 2-3-minute segment of the motor examination for each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted kappa statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted kappa = 0.67; standard error (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted kappa 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show Substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients. (c) 2004 Movement Disorder Society. C1 Oregon Hlth Sci Univ, Portland, OR 97239 USA. Univ Rochester, Rochester, NY USA. Columbia Univ, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hogarth, P (reprint author), Oregon Hlth Sci Univ, 3181 SW Sam Jackson Pk Rd,OP32, Portland, OR 97239 USA. EM hogarthp@ohsu.edu RI Raymond, Lynn/A-6664-2010; OI Raymond, Lynn/0000-0002-8610-1042; Greenamyre, J. Timothy/0000-0003-3468-7878; Caress, James/0000-0002-5814-6083 FU NHGRI NIH HHS [HG 02499]; NINDS NIH HHS [NS40098, T32 NS 07338] NR 15 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2005 VL 20 IS 3 BP 293 EP 297 DI 10.1002/mds.20332 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 910EC UT WOS:000227912100003 PM 15584032 ER PT J AU Martin, FC Le, AT Handforth, A AF Martin, FC Le, AT Handforth, A TI Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications SO MOVEMENT DISORDERS LA English DT Article DE essential tremor; harmaline propranolol; ethanol; octanol ID ANIMAL-MODELS; ETHANOL; ALCOHOL; PROPRANOLOL; TRIAL AB No preclinical method to evaluate potential new medications for essential tremor (ET) is available currently. Although harmaline tremor is a well known animal model of ET, it has not found utility as a preclinical drug screen and has not been validated with anti-ET medications. We measured harmaline tremor in rats (10 mg/kg s.c.) and mice (20 mg/kg s.c.) with a load sensor under the cage floor and performed spectral analysis on 20-minute epochs. The motion power over the tremor frequency bandwidth (8-12 Hz in rats 10-16 Hz in mice) was divided by the motion power over the full motion frequency range (0-15 Hz in rats; 0-34 Hz in mice). The use of these measures greatly reduced data variability, permitting experiments with small sample sizes. Three drugs that suppress ET (propranolol, ethanol, and octanol) all significantly suppressed harmaline-induced tremor. We propose that, with this methodology, harmaline-induced tremor may be useful as a preclinical method to identify potential medications for ET. (c) 2004 Movement Disorder Society. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. RP Martin, FC (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, 11301 Wilshire Blvd,Bldg 114,Room 226, Los Angeles, CA 90073 USA. EM fredricka.martin@med.va.gov NR 29 TC 48 Z9 48 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2005 VL 20 IS 3 BP 298 EP 305 DI 10.1002/mds.20331 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 910EC UT WOS:000227912100004 PM 15580562 ER PT J AU Griffin, JD AF Griffin, JD TI Interaction maps for kinase inhibitors SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID MYELOID-LEUKEMIA; LUNG-CANCER; MUTATIONS; IMATINIB; ABL; GEFITINIB; GENE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu NR 13 TC 9 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2005 VL 23 IS 3 BP 308 EP 309 DI 10.1038/nbt0305-308 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 906IW UT WOS:000227635400016 PM 15765084 ER PT J AU Ntziachristos, V Ripoll, J Wang, LHV Weissleder, R AF Ntziachristos, V Ripoll, J Wang, LHV Weissleder, R TI Looking and listening to light: the evolution of whole-body photonic imaging SO NATURE BIOTECHNOLOGY LA English DT Article ID DIFFUSE OPTICAL TOMOGRAPHY; IN-VIVO; FLUORESCENCE TOMOGRAPHY; BIOLUMINESCENCE TOMOGRAPHY; SCATTERING MEDIA; CONTRAST AGENTS; TURBID MEDIA; RECONSTRUCTION; TISSUE; TUMORS AB Optical imaging of live animals has grown into an important tool in biomedical research as advances in photonic technology and reporter strategies have led to widespread exploration of biological processes in vivo. Although much attention has been paid to microscopy, macroscopic imaging has allowed small-animal imaging with larger fields of view (from several millimeters to several centimeters depending on implementation). Photographic methods have been the mainstay for fluorescence and bioluminescence macroscopy in whole animals, but emphasis is shifting to photonic methods that use tomographic principles to noninvasively image optical contrast at depths of several millimeters to centimeters with high sensitivity and sub-millimeter to millimeter resolution. Recent theoretical and instrumentation advances allow the use of large data sets and multiple projections and offer practical systems for quantitative, three-dimensional whole-body images. For photonic imaging to fully realize its potential, however, further progress will be needed in refining optical inversion methods and data acquisition techniques. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece. Texas A&M Univ, Dept Biomed Engn, Opt Imaging Lab, College Stn, TX 77843 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, CNY149,13th St 5406, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu RI Wang, Lihong/A-7147-2009; Ripoll, Jorge/J-8134-2012 OI Wang, Lihong/0000-0001-9783-4383; Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R33 CA91807, 1-N01-CO027105, P01 CA69246, P50 CA86355, R24 CA92782, R33 CA091807]; NIAID NIH HHS [P01 AI054904]; NIBIB NIH HHS [R01EB000750-1] NR 58 TC 925 Z9 968 U1 19 U2 160 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2005 VL 23 IS 3 BP 313 EP 320 DI 10.1038/nbt1074 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 906IW UT WOS:000227635400018 PM 15765087 ER PT J AU Yoshida, K Yamaguchi, T Natsume, T Kufe, D Miki, Y AF Yoshida, K Yamaguchi, T Natsume, T Kufe, D Miki, Y TI JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage SO NATURE CELL BIOLOGY LA English DT Article ID TYROSINE KINASE; 14-3-3 PROTEINS; SUBCELLULAR-LOCALIZATION; STRESS; CELLS; BCR; SPECIFICITY; BINDING; DEATH; DELTA AB The ubiquitously expressed c-Abl tyrosine kinase localizes to the cytoplasm and nucleus(1,2). Nuclear c-Abl is activated by diverse genotoxic agents and induces apoptosis(3,4); however, the mechanisms that are responsible for nuclear targeting of c-Abl remain unclear. Here, we show that cytoplasmic c-Abl is targeted to the nucleus in the DNA damage response. The results show that c-Abl is sequestered into the cytoplasm by binding to 14-3-3 proteins. Phosphorylation of c-Abl on Thr 735 functions as a site for direct binding to 14-3-3 proteins. We also show that, in response to DNA damage, activation of the c-Jun N-terminal kinase (Jnk) induces phosphorylation of 14-3-3 proteins and their release from c-Abl. Together with these results, expression of an unphosphorylated 14-3-3 mutant attenuates DNA-damage-induced nuclear import of c-Abl and apoptosis. These findings indicate that 14-3-3 proteins are pivotal regulators of intracellular c-Abl localization and of the apoptotic response to genotoxic stress. C1 Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Genet, Tokyo 1138510, Japan. Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Kohtoh Ku, Tokyo 1350064, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yoshida, K (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Genet, Tokyo 1138510, Japan. EM yos.mgen@mri.tmd.ac.jp; miki.mgen@mri.tmd.ac.jp FU NCI NIH HHS [CA29431, CA98628] NR 28 TC 156 Z9 165 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2005 VL 7 IS 3 BP 278 EP U97 DI 10.1038/ncb1228 PG 12 WC Cell Biology SC Cell Biology GA 902CU UT WOS:000227329800016 PM 15696159 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, RP Braunwald, E TI 2004 ACC/AHA guideline for the management of patients with STEMI: the implications for clinicians SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material ID LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; HEART-FAILURE; MORTALITY; TRIAL C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 10 TC 13 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD MAR PY 2005 VL 2 IS 3 BP 114 EP 115 DI 10.1038/ncpcardio0135 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 925QX UT WOS:000229068900002 PM 16265435 ER PT J AU Yucel, EK AF Yucel, EK TI Magnetic resonance angiography and the peripheral vasculature: how useful is it? SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material DE atherosclerosis; magnetic resonance angiography; magnetic resonance imaging ID MR-ANGIOGRAPHY; DISEASE C1 Boston Vet Adm Hosp, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Yucel, EK (reprint author), Boston VA Healthcare Syst, W Roxbury Div, 1400 VFW Pkwy, Boston, MA 02132 USA. EM kent.yucel@med.va.gov NR 3 TC 0 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD MAR PY 2005 VL 2 IS 3 BP 136 EP 137 DI 10.1038/ncpcardio0131 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 925QX UT WOS:000229068900010 PM 16265456 ER PT J AU Sonis, ST AF Sonis, ST TI Is oral mucositis an inevitable consequence of intensive therapy for hematologic cancers? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE chemotherapy; hematologic cancer; mucositis; palifermin; radiotherapy C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org NR 4 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD MAR PY 2005 VL 2 IS 3 BP 134 EP 135 DI 10.1038/ncponc0104 PG 2 WC Oncology SC Oncology GA 926JH UT WOS:000229119000008 PM 16264905 ER PT J AU Oshima, K Heller, S AF Oshima, K Heller, S TI Sound from silence SO NATURE MEDICINE LA English DT Editorial Material ID MAMMALIAN INNER-EAR; HAIR-CELLS; MATH1; GENERATION; EXPRESSION; GENE; HES1 C1 Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Oshima, K (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. EM Stefan_Heller@meei.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2005 VL 11 IS 3 BP 249 EP 250 DI 10.1038/nm0305-249 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 905BA UT WOS:000227541300013 PM 15746932 ER PT J AU Peters, BA Diaz, LA Polyak, K Meszler, L Romans, K Guinan, EC Antin, JH Myerson, D Hamilton, SR Vogelstein, B Kinzler, KW Lengauer, C AF Peters, BA Diaz, LA Polyak, K Meszler, L Romans, K Guinan, EC Antin, JH Myerson, D Hamilton, SR Vogelstein, B Kinzler, KW Lengauer, C TI Contribution of bone marrow-derived endothelial cells to human tumor vasculature SO NATURE MEDICINE LA English DT Article ID PROGENITOR CELLS; ANGIOGENESIS; GROWTH; HEPATOCYTES; FUSION AB It has been shown that bone marrow-derived stem cells can form a major fraction of the tumor endothelium in mouse tumors. To determine the role of such cells in human tumor angiogenesis, we studied six individuals who developed cancers after bone marrow transplantation with donor cells derived from individuals of the opposite sex. By performing fluorescence in situ hybridization (FISH) with sex chromosome-specific probes in conjunction with fluorescent antibody staining, we found that such stem cells indeed contributed to tumor endothelium, but at low levels, averaging only 4.9% of the total. These results illustrate substantial differences between human tumors and many mouse models with respect to angiogenesis and have important implications for the translation of experimental antiangiogenic therapies to the clinic. C1 Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21231 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Div Pathol & Lab Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematopathol, Div Pathol & Lab Med, Houston, TX 77030 USA. RP Lengauer, C (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St, Baltimore, MD 21231 USA. EM lengauer@jhmi.edu FU NCI NIH HHS [CA57345] NR 15 TC 338 Z9 370 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2005 VL 11 IS 3 BP 261 EP 262 DI 10.1038/nm1200 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 905BA UT WOS:000227541300019 PM 15723071 ER PT J AU Patil, VRS Friedrich, EB Wolley, AE Gerszten, RE Allport, JR Weissleder, R AF Patil, VRS Friedrich, EB Wolley, AE Gerszten, RE Allport, JR Weissleder, R TI Bone marrow-derived lin(-)c-kit(+)Sca-1(+) stem cells do not contribute to vasculogenesis in Lewis lung carcinoma SO NEOPLASIA LA English DT Article DE stem cells; vasculogenesis; angiogenesis; tumors; chemokine ID ENDOTHELIAL PROGENITOR CELLS; TUMOR ANGIOGENESIS; IN-VIVO; NEOVASCULARIZATION; TRANSPLANTATION; MOBILIZATION; RECRUITMENT; MECHANISMS; ORIGIN; GROWTH AB The development of tumor vasculature is thought to occur through two complementary processes: sprouting angiogenesis from preexisting blood vessels of the host, and vasculogenesis, which involves the spontaneous development of vessels through specific recruitment, differentiation, and vascular incorporation of circulating endothelial cells (EC), endothelial progenitor cells (EPC), or potentially bone marrow-derived cells. Recent reports, however, have challenged the belief that bone marrow-derived cells contribute to tumor neovascularization, claiming an exclusive role for sprouting angiogenesis in tumor blood vessel development. In the present study, we explored the recruitment behavior of bone marrow-derived lin(-)c-kit(+)Sca-1(+) stem cells to subcutaneously implanted Lewis lung carcinoma in a syngeneic bone marrow transplantation model. We observed that although lin(-)c-kit(+)Sca-1(+) and their derived cells demonstrate significant recruitment to carcinomas in vivo, they do not appear to functionally contribute to tumor neovascularization. Furthermore, our results support the hypothesis that new vessel formation in carcinomas occurs primarily through endothelialization from adjacent and preexisting vasculature. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Allport, JR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM jennifer-allport@hms.harvard.edu NR 32 TC 24 Z9 24 U1 0 U2 1 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAR PY 2005 VL 7 IS 3 BP 234 EP 240 DI 10.1593/neo.04523 PG 7 WC Oncology SC Oncology GA 910IS UT WOS:000227925200005 ER PT J AU de Vasconcelos, AP Bouilleret, V Riban, V Wasterlain, C Nehlig, A AF de Vasconcelos, AP Bouilleret, V Riban, V Wasterlain, C Nehlig, A TI Role of nitric oxide in cerebral blood flow changes during kainate seizures in mice: genetic and pharmacological approaches SO NEUROBIOLOGY OF DISEASE LA English DT Article DE neuronal nitric oxide synthase; knockout mice; 7-nitroindazole; kainate seizures; intrahippocampal injection; cerebral blood flow ID TEMPORAL-LOBE EPILEPSY; KAINIC ACID; HIPPOCAMPAL SCLEROSIS; SYNTHASE GENE; ELECTRICAL-STIMULATION; STATUS EPILEPTICUS; 7-NITRO INDAZOLE; LIMBIC SEIZURES; RAT-BRAIN; INHIBITION AB The role of neuronal nitric oxide (NO) in the cerebrovascular response to partial seizures induced by intrahippocampal injection of kainate (KA) was investigated in mice deleted for the neuronal NO synthase gene (nNOS-/-) and in wild-type controls (WT). A second group of WT mice received the nNOS inhibitor, 7-nitroindazole (WT-7NI). Local cerebral blood flow (LCBF) was measured using the quantitative C-14-iodoantipyrine method. Within the epileptic focus, all three groups of seizing mice (WT, WT-7NI, and nNOS-/-) showed significant 26-88% LCBF increases in ipsilateral hippocampus, compared to saline-injected mice. Contralaterally to the epileptic focus, KA seizures induced a 21-47% LCBF decreases in hippocampus and limbic cortex of WT mice and in most contralateral brain structures of nNOS-/- mice, while WT-7NI mice showed no contralateral CBF change. Neuronal NO appears to be not involved in the cerebrovascular response within the epileptic focus, but may rather have a role in the maintenance of distant LCBF regulation during seizures. (C) 2004 Elsevier Inc. All rights reserved. C1 Fac Med Strasbourg, INSERM U398, F-67085 Strasbourg, France. Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA USA. RP de Vasconcelos, AP (reprint author), ULP, CNRS, UMR 7521, LN2C, 12 Rue Goethe, F-67000 Strasbourg, France. EM Pereira@neurochem.u-strasbg.fr NR 70 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2005 VL 18 IS 2 BP 270 EP 281 DI 10.1016/j.nbd.2004.09.014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 896RC UT WOS:000226950200003 PM 15686955 ER PT J AU Hallett, PJ Dunah, AW Ravenscroft, P Zhou, S Bezard, E Crossman, AR Brotchie, JM Standaert, DG AF Hallett, PJ Dunah, AW Ravenscroft, P Zhou, S Bezard, E Crossman, AR Brotchie, JM Standaert, DG TI Alterations of striatal NMDA receptor subunits associated with the development of dyskinesia in the MPTP-lesioned primate model of Parkinson's disease SO NEUROPHARMACOLOGY LA English DT Article DE basal ganglia; trafficking; dopamine; glutamate; levodopa; macaque ID ASPARTATE GLUTAMATE RECEPTORS; BASAL GANGLIA; TYROSINE PHOSPHORYLATION; ANTIPARKINSONIAN ACTIONS; L-DOPA; MOTOR COMPLICATIONS; MESSENGER-RNAS; ANIMAL-MODELS; LEVODOPA; RAT AB The development of dyskinesias and other motor complications greatly limits the use of levodopa therapy in Parkinson's disease (PD). Studies in rodent models of PD suggest that an important mechanism underlying the development of levodopa-related motor complications is alterations in striatal NMDA receptor function. We examined striatal NMDA receptors in the MPTP-lesioned primate model of PD. Quantitative immunoblotting was used to determine the subcellular abundance of NR1, NR2A and NR2B subunits in striata from unlesioned, MPTP-lesioned (parkinsonian) and MPTP-lesioned, levodopa-treated (dyskinetic) macaques. In parkinsonian macaques, NR1 and NR2B subunits in synaptosomal membranes were decreased to 66 +/- 11% and 51.2 +/- 5 % of unlesioned levels respectively, while the abundance of NR2A was unaltered. Levodopa treatment eliciting dyskinesia normalized NR1 and NR2B and increased NR2A subunits to 150 +/- 12% of unlesioned levels. No alterations in receptor subunit tyrosine phosphorylation were detected. These results demonstrate that altered synaptic abundance of NMDA receptors with relative enhancement in the abundance of NR2A occurs in primate as well as rodent models of parkinsonism, and that in the macaque model, NR2A subunit abundance is further increased in dyskinesia. These data support the view that alterations in striatal NMDA receptor systems are responsible for adaptive and maladaptive responses to dopamine depletion and replacement in parkinsonism, and highlight the value of subtype selective NMDA antagonists as novel therapeutic approaches for PD. (c) 2004 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Manchester, Div Neurosci, Manchester M13 9PT, Lancs, England. Univ Bordeaux 2, CNRS, UMR 5543, Neurophysiol Lab, F-33076 Bordeaux, France. Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. RP Hallett, PJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM phallett@partners.org OI zhou, shaobo/0000-0001-5214-2973; Hallett, Penelope/0000-0002-8858-9096; Bezard, Erwan/0000-0002-0410-4638; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS34361] NR 48 TC 115 Z9 117 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAR PY 2005 VL 48 IS 4 BP 503 EP 516 DI 10.1016/j.neuropharm.2004.11.008 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 912NZ UT WOS:000228087300004 PM 15755478 ER PT J AU Lawton, MT Quinones-Hinojosa, A Chang, EF Yu, T AF Lawton, MT Quinones-Hinojosa, A Chang, EF Yu, T TI Thrombotic intracranial aneurysms: Classification scheme and management strategies in 68 patients SO NEUROSURGERY LA English DT Article DE bypass; endovascular coiling; intracranial aneurysm; microsurgical clipping; thrombectomy; thrombotic ID GUGLIELMI DETACHABLE COILS; BASILAR ARTERY ANEURYSM; TECHNICAL CASE-REPORT; SAPHENOUS-VEIN GRAFT; CEREBRAL REVASCULARIZATION; INTRAOPERATIVE ANGIOGRAPHY; SURGICAL-TREATMENT; GIANT ANEURYSMS; FUSIFORM; SURGERY AB OBJECTIVE: Thrombotic aneurysms are a diverse collection of complex aneurysms characterized by organized intraluminal thrombus and solid mass. Consequently, their treatment often requires techniques other than conventional clipping, such as thrombectomy with clip reconstruction or bypass with parent artery occlusion. A single-surgeon experience with thrombotic aneurysms was analyzed to determine optimal treatment strategies. A classification scheme was devised on the basis of aneurysm, thrombus, and lumen morphology to relate these anatomic features to surgical therapy. METHODS: Sixty-eight patients with thrombotic aneurysms were managed during a period of 6.25 years. Thrombotic aneurysms were classified into six types: concentric (n = 17, 25%), eccentric (n = 14, 21%), lobulated (n = 2, 3%), complete (n = 2, 3%), canalized (n = 17, 25%), and coiled (n = 16, 24%). RESULTS: Aneurysm management consisted of direct clipping (n 22, 32%), thrombectomy-clip reconstruction (n = 18, 26%), bypass-occlusion (n 20, 29%), other (n = 6, 9%), or observation (n = 2, 3%). Complete angiographic obliteration was achieved in 97% of patients, and 47% of aneurysms were thrombectornized. The surgical mortality rate was 6%, and the permanent neurological morbidity rate was 7%. Overall, 87% of patients were improved or unchanged at follow-up, with 79% reaching a Glasgow Outcome Scale score of 5 or 4. Management strategy was influenced by thrombotic aneurysm type, but patient outcome was not. The best results were observed in patients treated with direct clipping and bypass-occlusion. CONCLUSION: Despite their solid mass, one-third of thrombotic aneurysms can be treated surgically with conventional clipping. Direct clipping is associated with the best surgical results, and the proposed classification scheme identifies thrombotic aneurysms that may be clippable. Patients with unclippable thrombotic aneurysms had more favorable results when treated with bypass and aneurysm occlusion than with thrombectomy and clip reconstruction. The classification scheme may provide conceptual clarity and therapeutic guidance with preoperative and intraoperative decision making. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lawton, MT (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,M-780C, San Francisco, CA 94143 USA. EM lawtonm@neurosurg.ucsf.edu NR 45 TC 47 Z9 53 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 2005 VL 56 IS 3 BP 441 EP 453 DI 10.1227/01.NEU.0000153927.70897.A2 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 905IP UT WOS:000227562100017 PM 15730569 ER PT J AU Buerhaus, PI Donelan, K Ulrich, BT Norman, L Dittus, R AF Buerhaus, PI Donelan, K Ulrich, BT Norman, L Dittus, R TI Is the shortage of hospital registered nurses getting better or worse? Findings from two recent national surveys of RNs SO NURSING ECONOMICS LA English DT Article ID CARE AB In surveys conducted in 2 and 2004, nurse perceptions of the workforce shortage were assessed with respect to its current state, effects on practice, directional trends, and causes and solutions. In 2004, nurses perceived less of a gap between supply and demand than respondents in 2002. Fewer nurses in 2004 (41%) perceived salary and benefits as main causes of the shortage than in 2002 (58%). In 2004, nurses were asked about recruitment and retention efforts in terms of their perceived potential benefit and perceived use. While most recruitment and retention strategies were perceived as valuable by at least half of the nurses surveyed, only one retention strategy was observed by more than half of the nurses surveyed: mentoring programs for new grads. C1 Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Nursing Spectrum Nurse Week, Profess Serv, Pearland, TX USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. NR 16 TC 51 Z9 51 U1 0 U2 1 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 MAR-APR PY 2005 VL 23 IS 2 BP 61 EP + PG 12 WC Nursing SC Nursing GA 046HH UT WOS:000237801700003 PM 15881491 ER PT J AU Meigs, JB Hu, FB Perhanidis, JS Hunter, D Rifai, N Manson, JE AF Meigs, JB Hu, FB Perhanidis, JS Hunter, D Rifai, N Manson, JE TI E-selectin genotypes and risk of type 2 diabetes in women SO OBESITY RESEARCH LA English DT Article DE E-selectin; genetics; type 2 diabetes; epidemiology; risk factors ID CORONARY-ARTERY-DISEASE; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; ADIPOSE-TISSUE; ENDOTHELIAL DYSFUNCTION; S128R POLYMORPHISM; MELLITUS; ATHEROSCLEROSIS; OBESITY AB Endothelial dysfunction increases risk for type 2 diabetes. We examined whether variation in the gene for E-selectin (SELE), a biomarker of endothelial dysfunction, was associated with levels of E-selectin or diabetes quantitative traits (including fasting levels of insulin and hemoglobin Ale) in 719 nondiabetic participants of the Nurses' Health Study or with risk of diabetes in 602 incident (over 10 years of follow-up) cases and 655 control women matched for age, race, and fasting status. Variation in three single nucleotide polymorphisms previously associated with cardiovascular disease risk and having effects on E-selectin function, S128R, G98T, and L554F, was not significantly (p > 0.05) associated with levels of E-selectin or diabetes quantitative traits, or with risk of incident diabetes in the primary analysis. Among women with low levels of subclinical inflammation (C-reactive protein levels below the population median), S128R R allele carriers had a diabetes risk factor-adjusted relative risk of incident diabetes of 1.71 (95% confidence interval, 1.04 to 2.81) relative to those with the SS genotype. Apart from an association in this subgroup, we conclude that the E-selectin variants we examined are not important genetic risk factors for type 2 diabetes in women. C1 Massachusetts Gen Hosp, Gen Internal Med Unit, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Childrens Hosp, Ctr Med, Dept Pathol, Boston, MA 02115 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, Div Gen Med, Dept Med, 50 Staniford St,Floor 9, Boston, MA 02114 USA. EM jmeigs@partners.org FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845, DK46519, DK36798] NR 31 TC 7 Z9 7 U1 1 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAR PY 2005 VL 13 IS 3 BP 513 EP 518 DI 10.1038/oby.2005.54 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 919NT UT WOS:000228625500006 PM 15833936 ER PT J AU Lu, KH Dinh, M Kohlmann, W Watson, P Green, J Syngal, S Bandipalliam, P Chen, LM Allen, B Conrad, P Terdiman, J Sun, C Daniels, M Burke, T Gershenson, DM Lynch, H Lynch, P Broaddus, RR AF Lu, KH Dinh, M Kohlmann, W Watson, P Green, J Syngal, S Bandipalliam, P Chen, LM Allen, B Conrad, P Terdiman, J Sun, C Daniels, M Burke, T Gershenson, DM Lynch, H Lynch, P Broaddus, RR TI Gynecologic cancer as a "sentinel cancer" for women with hereditary nonpolyposis colorectal cancer syndrome SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Gynecologic-Oncologists CY FEB 07-11, 2004 CL San Diego, CA SP Soc Gynecol Oncol ID ENDOMETRIAL CANCER; MUTATION ANALYSIS; FAMILY SYNDROME; LYNCH-SYNDROME; RISK; CARCINOMA; HOMOLOG AB OBJECTIVE: Women with hereditary nonpolyposis colorectal cancer syndrome have a 40 - 60% lifetime risk for colon cancer, a 40 - 60% lifetime risk for endometrial cancer, and a 12% lifetime risk for ovarian cancer. A number of women with hereditary nonpolyposis colorectal cancer syndrome will have more than one cancer in their lifetime. The purpose of this study was to estimate whether women with hereditary nonpolyposis colorectal cancer syndrome who develop 2 primary cancers present with gynecologic or colon cancer as their "sentinel cancer." METHODS: Women whose families fulfilled Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome and who developed 2 primary colorectal/gynecologic cancers in their lifetime were identified from 5 large hereditary nonpolyposis colorectal cancer syndrome registries. Information on age at cancer diagnoses and which cancer (colon cancer or endometrial cancer/ovarian cancer) developed first was obtained. RESULTS: A total of 117 women with dual primary cancers from 223 Amsterdam families were identified. In 16 women, colon cancer and endometrial cancer/ovarian cancer were diagnosed simultaneously. Of the remaining 101 women, 52 (51%) women had an endometrial or ovarian cancer diagnosed first. Forty-nine (49%) women had a colon cancer diagnosed first. For women who developed endometrial cancer/ovarian cancer first, mean age at diagnosis of endometrial cancer/ovarian cancer was 44. For women who developed colon cancer first, the mean age at diagnosis of colon cancer was 40. CONCLUSION: In this large series of women with hereditary nonpolyposis colorectal cancer syndrome who developed 2 primary colorectal/gynecologic cancers, endometrial cancer/ovarian cancer was the "sentinel cancer," preceding the development of colon cancer, in half of the cases. Therefore, gynecologists and gynecologic oncologists play a pivotal role in the identification of women with hereditary nonpolyposis colorectal cancer syndrome. (C) 2005 by The American College of Obstetricians and Gynecologists. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Div Surg, Houston, TX 77030 USA. Creighton Univ, Omaha, NE 68178 USA. Mem Univ Newfoundland, St Johns, NF A1C 5S7, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Lu, KH (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Div Surg, 1515 Holcombe Blvd,Unit 440, Houston, TX 77030 USA. EM khlu@mdanderson.org RI Parashar, Rajni/J-8511-2012; OI Daniels, Molly/0000-0002-5093-5539 FU NCI NIH HHS [N01-CN-05127] NR 21 TC 136 Z9 147 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2005 VL 105 IS 3 BP 569 EP 574 DI 10.1097/01.AOG.0000154885.44002.ae PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 900IZ UT WOS:000227209900020 PM 15738026 ER PT J AU Kim, JY Chen, JC Kim, JY Christiani, DC AF Kim, JY Chen, JC Kim, JY Christiani, DC TI Exposure to welding fumes is associated with acute systemic inflammatory responses SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; PARTICULATE AIR-POLLUTION; RESPIRATORY SYMPTOMS; CARDIOVASCULAR-DISEASE; PULMONARY-FUNCTION; MONICA-AUGSBURG; BLOOD MARKERS; CELL COUNT; WELDERS AB Aims: To investigate the acute systemic inflammatory response to welding fume exposure. Methods: Twenty four welders (42% smokers) and 13 non-exposed controls (23% smokers) were monitored at a welding school. Exposure to fine particulate matter (PM2.5) was assessed using cyclone samplers. Markers of systemic inflammation, including C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) levels, were determined in peripheral blood samples collected at baseline and after 5.3 (SD 1.0) hours of exposure. Results: The median PM2.5 concentration for welders was 1.66 mg/m(3), which was significantly greater than that for controls (0.04 mg/m(3)). Compared to non-smokers, smokers had a significantly higher baseline WBC count, but comparable levels of CRP and fibrinogen. In non-smokers, welding fume exposure was associated with a significant increase in WBC and neutrophil counts immediately following exposure (+ 0.8 x 10(3)/mul, 95% CI 0.1 to 1.6, and + 1.0 x 10(3)/mul, 95% CI 0.4 to 1.7, respectively). A significant decrease in fibrinogen levels was observed in non-smokers (-32 mg/dl, 95% CI -63 to -1). No significant changes in WBC, neutrophil, and fibrinogen levels were found in smokers. Sixteen hours after welding exposure, CRP levels were found to be significantly increased in both non-smokers and smokers (0.90 mg/l, 95% CI 0.17 to 1.64). PM2.5 concentrations were found to be significantly associated with absolute neutrophil counts in non-smokers, and CRP levels in both non-smokers and smokers. Conclusions: High levels of welding fume exposure induce acute systemic inflammation in a relatively young, healthy working population. These results also suggest that smoking may modify the effect of welding fume exposure on specific inflammatory markers. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Room 1402,665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Chen, JC/I-2261-2016 FU NCI NIH HHS [CA94715]; NIEHS NIH HHS [ES09860, T32 ES07069, ES00002]; PHS HHS [T42110421] NR 37 TC 48 Z9 50 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAR PY 2005 VL 62 IS 3 BP 157 EP 163 DI 10.1136/oem.2004.014795 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 904BM UT WOS:000227470100006 PM 15723880 ER PT J AU Posner, MR AF Posner, MR TI Adjuvant post-operative chemoradiotherapy in Head and Neck Cancer: A standard of care? SO ONCOLOGIST LA English DT Editorial Material ID LOCALLY ADVANCED HEAD; RANDOMIZED-TRIAL; RADIOTHERAPY; CHEMOTHERAPY; CARCINOMA C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. NR 8 TC 0 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAR PY 2005 VL 10 IS 3 BP 174 EP 175 DI 10.1634/theoncologist.10-3-174 PG 2 WC Oncology SC Oncology GA 911UQ UT WOS:000228031500001 PM 15793219 ER PT J AU Shipley, WU AF Shipley, WU TI The Fernando/Sandler article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID INVASIVE BLADDER-CANCER; CYSTECTOMY; CARCINOMA; SURGERY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Chair Clin Res, Boston, MA 02115 USA. RP Shipley, WU (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Chair Clin Res, Boston, MA 02115 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2005 VL 19 IS 3 BP 339 EP + PG 3 WC Oncology SC Oncology GA 052ED UT WOS:000238213300013 ER PT J AU Epshtein, A Bauer-Wu, S AF Epshtein, A Bauer-Wu, S TI Improving the quality of nursing research: A research approval process. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 3 BP 422 EP 423 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400029 ER PT J AU Cashavelly, B Temel, J Pirl, W AF Cashavelly, B Temel, J Pirl, W TI Collaborating to improve cancer-related fatigue: A multi-disciplinary thoracic oncology team implements the NCCN guidelines for screening cancer-related fatigue in the ambulatory setting. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 2005 VL 32 IS 2 MA 31 BP 431 EP 431 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400057 ER PT J AU Virchick, B AF Virchick, B TI End of life care. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 47 BP 435 EP 436 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400080 ER PT J AU Fitzgerald, E Cashavelly, B LaFrancesca, J Mannix, C Somerville, J AF Fitzgerald, E Cashavelly, B LaFrancesca, J Mannix, C Somerville, J TI Oncology nursing retreat: Creating a community for cancer nursing practice. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 69 BP 441 EP 442 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400094 ER PT J AU O'Dette, E McElhinny, M AF O'Dette, E McElhinny, M TI Strategies to promote spiritual well-being in patients with cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 119 BP 455 EP 455 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400144 ER PT J AU Fonteyn, M Vettese, M Hayes, C Hanley, D Bauer-Wu, S AF Fonteyn, M Vettese, M Hayes, C Hanley, D Bauer-Wu, S TI Using a working group to encourage and facilitate scholarship among nurse clinicians and managers. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 133 BP 459 EP 459 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400158 ER PT J AU Perryman, S AF Perryman, S TI Cross cultural education: Implications for oncology nursing practice. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 139 BP 461 EP 461 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400164 ER PT J AU Ott, MJ AF Ott, MJ TI Yoga at your desk: Self care and stress management for the busy clinician. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 MAR PY 2005 VL 32 IS 2 MA 144 BP 462 EP 462 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400169 ER PT J AU Kelly-Colson, K AF Kelly-Colson, K TI Nursing challenges for treating relapsed multiple myeloma with bortezomib (velcade) compared with high-dose dexamethasone. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 176 BP 471 EP 471 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400201 ER PT J AU Maloof, D Lowell, J Prisby, J AF Maloof, D Lowell, J Prisby, J TI Clinical research nursing challenge: Calming nurses fears when using smallpox vaccine as cutting edge cancer therapy. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 MAR PY 2005 VL 32 IS 2 MA 224 BP 485 EP 486 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400249 ER PT J AU O'Connor, J Conlin, G Decristofaro, S Saint-Eloi, SE Gaumer, C Reid-Ponte, P AF O'Connor, J Conlin, G Decristofaro, S Saint-Eloi, SE Gaumer, C Reid-Ponte, P TI Bridging the gap: Designing an oncology nursing consult service. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 2005 VL 32 IS 2 MA 249 BP 493 EP 493 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400273 ER PT J AU Saint-Eloi, S Tracey, E Hanley, D Conlin, G Buia, S AF Saint-Eloi, S Tracey, E Hanley, D Conlin, G Buia, S TI Development of a nurse-sensitive dashboard to implement the staffing effectiveness standard in an outpatient oncology setting. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAR PY 2005 VL 32 IS 2 MA 259 BP 495 EP 496 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400283 ER PT J AU Szlyk, JP Seiple, W Stelmack, J McMahon, T AF Szlyk, JP Seiple, W Stelmack, J McMahon, T TI Use of prisms for navigation and driving in hemianopic patients SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS LA English DT Article DE devices; driving; follow-up; hemianopsia; low vision; prisms ID VISUAL-FIELD LOSS; HOMONYMOUS HEMIANOPIA; CONTRAST SENSITIVITY; RETINITIS-PIGMENTOSA; PERFORMANCE; VISION; AGE AB Purpose: (1) To compare the outcomes of orientation and mobility and driving training with Fresnel prisms and the Gottlieb Visual Field Awareness System for patients with homonymous hemianopsia, and (2) To determine whether the patients continue to use the optical enhancement devices at a 2-year follow-up point. Methods: Patients with homonymous hemianopsia were provided with a rehabilitation program where they were fitted with prism lenses and trained to use them for navigation and driving. Telephone interviews were used to obtain information about device usage 2 years following the completion of the training program. Results: Patients' performance was compared with a test-retest criterion in the visual skills areas of recognition, mobility, peripheral detection, scanning, tracking, and visual memory. Patients with hemianopic loss showed improvements in all of the visual skills categories, ranging from the highest improvements of 26% of tasks improved in the mobility category to 13% in the recognition category. The majority of the hemianopic patients reported using the devices at the 2-year follow-up interview. Conclusions: The patients with homonymous hemianopsia showed improvements in visual functioning using prism lenses, although these improvements were smaller than those found in previous studies with central or bilateral peripheral vision loss groups who were trained to use other optical enhancement devices for navigation and driving using a similar curriculum. However, given the evidence of increased risk of accidents for patients with peripheral vision loss, the safety of peripheral enhancement devices for driving must be thoroughly evaluated before their impact on public safety is known. C1 VA Chicago Hlth Care Syst, W Side Div, Res & Dev Serv, Chicago, IL 60612 USA. Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL USA. NYU, Sch Med, Dept Ophthalmol, New York, NY USA. Illinois Coll Optometry, Chicago, IL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Blind Rehabil Ctr, Hines, IL 60141 USA. RP Szlyk, JP (reprint author), VA Chicago Hlth Care Syst, W Side Div, Res & Dev Serv, M-C 151,820 S Damen Ave, Chicago, IL 60612 USA. EM janeszly@uic.edu OI Seiple, William/0000-0002-5750-650X FU NEI NIH HHS [EY1792] NR 24 TC 24 Z9 25 U1 0 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0275-5408 J9 OPHTHAL PHYSL OPT JI Ophthalmic Physiol. Opt. PD MAR PY 2005 VL 25 IS 2 BP 128 EP 135 DI 10.1111/j.1475-1313.2004.00265.x PG 8 WC Ophthalmology SC Ophthalmology GA 901YP UT WOS:000227318500006 PM 15713204 ER PT J AU Taneri, S Azar, DT AF Taneri, S Azar, DT TI LASEK: results after 1 year. Retrospective analysis based on the dioptric power matrix for moderate myopic and astigmatic correction SO OPHTHALMOLOGE LA German DT Article DE refractive surgery; laser-assisted keratomileusis (LASEK); myopia; astigmatism; dioptric power matrix ID ASSISTED SUBEPITHELIAL KERATECTOMY; EPITHELIAL KERATOMILEUSIS LASEK; PHOTOREFRACTIVE KERATECTOMY; FOLLOW-UP; SURGERY; ELSA; EYES AB Purpose. The aim of this study was to assess astigmatism magnitude and axis changes based on the dioptric power matrix in low to moderate levels of myopia and astigmatism treated with LASEK. Patients and methods. This retrospective analysis included 54 myopic eves treated with LASEK with a minimum follow-up of 12 months. An epithelial flap was created by 24-45 s of 20% alcohol exposure. The corneal surface was ablated using two different excimer lasers and nomogram adjustment. The flap was repositioned and a bandage applied to the contact lens. Main outcome measures were manifest refraction as calculated with the dioptric power matrix, UCVA, BSVCA, and retreatment rate. Results. Mean manifest refraction is shown in table 2 (boxed dot Tabelle 2). UCVAs of 20/20 or better were found in 33% of eyes at 1 week and in more than 53% at 3 months to 1 year. The safety index remained >= 0.98 after postoperative week 4. The efficacy index varied between 0.91 and 0.98 after 1 month. Conclusion. LASEK for correction of low to moderate myopia and astigmatism seems to be a safe, effective, and stable option. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Taneri, S (reprint author), Hohenzollerklin, Zentrum Refrakt Chirurg Munster, Hohenzollerning, D-48145 Munster, Germany. EM taneri@refraktives-zentrum.de NR 34 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-293X J9 OPHTHALMOLOGE JI Ophthalmologe PD MAR PY 2005 VL 102 IS 3 BP 235 EP 240 DI 10.1007/s00347-004-1097-y PG 6 WC Ophthalmology SC Ophthalmology GA 910WG UT WOS:000227962300006 PM 15578186 ER PT J AU Ring, D Jupiter, JB AF Ring, David Jupiter, Jesse B. TI Treatment of osteoporotic distal radius fractures SO OSTEOPOROSIS INTERNATIONAL LA English DT Review DE Bone; Distal radius; External fixation; Internal fixation; Osteoporosis; Wrist AB Fracture of distal radius is most commonly an injury of the fit osteoporotic patient. As the population and health of older individuals continue to expand, osteoporotic distal radius fractures will become increasingly common. While many older patients have limited functional demands and can accept some deformity and wrist dysfunction, others remain very active into older age and desire optimal wrist alignment and function. The difficulty obtaining reliable fixation in osteoporotic bone presents a challenge to the surgeon that has been partially addressed by newer implants with screws that directly engage the plate, creating fixed angle bolts that have better fixation in osteoporotic bone. Decision-making is based upon a balance of the goals of the individual patient with the risks of intervention. C1 [Ring, David; Jupiter, Jesse B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkee Ctr, Boston, MA 02114 USA. [Ring, David; Jupiter, Jesse B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkee Ctr, Suite 2100,Fruit Str, Boston, MA 02114 USA. EM dring@partners.org NR 28 TC 38 Z9 39 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2005 VL 16 SU 2 BP S80 EP S84 DI 10.1007/s00198-004-1808-x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V06CX UT WOS:000207172800011 PM 15614440 ER PT J AU Merchant, SN Adams, JC Nadol, JB AF Merchant, SN Adams, JC Nadol, JB TI Pathology and pathophysiology of idiopathic sudden sensorineural hearing loss SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Neurotology-Society CY MAY 01-02, 2004 CL Phoenix, AZ SP Amer Neurotol Soc DE sensorineural hearing loss; sudden deafness; pathology ID NF-KAPPA-B; HUMAN TEMPORAL BONE; INNER-EAR; TRANSCRIPTION FACTORS; VIRAL LABYRINTHITIS; VIRUS-INFECTION; GUINEA-PIGS; DEAFNESS; HISTOPATHOLOGY; IMPAIRMENT AB Background: The cause and pathogenesis of idiopathic sudden sensorineural hearing loss remain unknown. Proposed theories include vascular occlusion, membrane breaks, and viral cochleitis. Aims: To describe the temporal bone histopathology in 17 ears (aged 45-94 yr) with idiopathic sudden sensorineural hearing loss in our temporal bone collection and to discuss the implications of the histopathologic findings with respect to the pathophysiology of idiopathic sudden sensorineural hearing loss. Methods: Standard light microscopy using hematoxylin and eosin-stained sections was used to assess the otologic abnormalities. Results: Hearing had recovered in two ears and no histologic correlates were found for the hearing loss in both ears. In the remaining 15 ears, the predominant abnormalities were as follows: 1) loss of hair cells and supporting cells of the organ of Corti (with or without atrophy of the tectorial membrane, stria vascularis, spiral limbus, and cochlear neurons) (13 ears); 2) loss of the tectorial membrane, supporting cells, and stria vascularis (I ear); and 3) loss of cochlear neurons only (I ear). Evidence of a possible vascular cause for the idiopathic sudden sensorineural hearing loss was observed in only one ear. No membrane breaks were observed in any ear. Only I of the 17 temporal bones was acquired acutely during idiopathic sudden sensorineural hearing loss, and this ear did not demonstrate any leukocytic invasion, hypervascularity, or hemorrhage within the labyrinth, as might be expected with a viral cochleitis. Discussion: The temporal bone findings do not support the concept of membrane breaks, perilymphatic fistulae, or vascular occlusion as common causes for idiopathic sudden sensorineural hearing loss. The finding in our one case acquired acutely during idiopathic sudden sensorineural hearing loss as well as other clinical and experimental observations do not strongly support the theory of viral cochleitis. Conclusion: We put forth the hypothesis that idiopathic sudden sensorineural hearing loss may be the result of pathologic activation of cellular stress pathways involving nuclear factor-kappa B within the cochlea. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Otopathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Otopathol Lab, 243 Charles St, Boston, MA 02114 USA. EM Saumil_merchant@meei.harvard.edu NR 42 TC 81 Z9 90 U1 0 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAR PY 2005 VL 26 IS 2 BP 151 EP 160 DI 10.1097/00129492-200503000-00004 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 957ZI UT WOS:000231411700004 PM 15793397 ER PT J AU Lim, G Wang, SX Zeng, Q Sung, B Mao, JR AF Lim, G Wang, SX Zeng, Q Sung, B Mao, JR TI Evidence for a long-term influence on morphie tolerance after previous morphine exposure: role of neuronal glucocorticoid receptors SO PAIN LA English DT Article DE opioid tolerance; morphine; glucocorticoid receptor; protein kinase A; cAMP; RU38486 ID ABNORMAL PAIN SENSITIVITY; PROTEIN KINASE-C; RAT SPINAL-CORD; ANALGESIC TOLERANCE; OPIOID THERAPY; MECHANISMS; MICE; ACTIVATION; EXPRESSION; DEXAMETHASONE AB Opioid analgesic tolerance is a pharmacological phenomenon that overtime diminishes the opioid analgesic effect. However, it remains unknown as to whether a previous opioid exposure would have a long-term influence on opioid tolerance upon subsequent opioid administration. Here, we show that the onset and degree of antinociceptive tolerance to a subsequent cycle of morphine exposure were substantially exacerbated in rats made tolerant to and then recovered from previous morphine administration, indicating a long-term influence from a previous morphine exposure on the development of morphine tolerance. Mechanistically, morphine exposure induced a cyclic AMP and protein kinase A-dependent upregulation of neuronal glucocorticoid receptors (GR) within the spinal cord dorsal horn, which was maintained after discontinuation of morphine administration and significantly enhanced upon a second cycle of morphine exposure. Prevention of the GR upregulation with GR antisense oligonucleotides as well as inhibition of GR activation with the GR antagonist RU38486 effectively prevented the exacerbated morphine tolerance after subsequent cycles of morphine exposure. The results indicate that a previous morphine exposure could induce lasting cellular changes mediated through neuronal GR and influence morphine analgesia upon a subsequent exposure. These findings may have significant implications in clinical opioid therapy and substance abuse. (c) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Anesthesia & Crit Car, Pain Res Grp,MGH Pain Ctr, Boston, MA 02116 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Anesthesia & Crit Car, Pain Res Grp,MGH Pain Ctr, 15 Parkman St,WACC 324, Boston, MA 02116 USA. EM jmao@partners.org FU NIDA NIH HHS [R01 DA08835]; NINDS NIH HHS [NS45681, NS42661] NR 50 TC 23 Z9 27 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2005 VL 114 IS 1-2 BP 81 EP 92 DI 10.1016/j.pain.2004.11.019 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 906ZI UT WOS:000227683500011 PM 15733634 ER PT J AU Zhuang, ZY Gerner, P Woolf, CJ Ji, RR AF Zhuang, ZY Gerner, P Woolf, CJ Ji, RR TI ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model SO PAIN LA English DT Article DE MAPK; ERK; microglia; astrocytes; spinal cord; neuropathic pain ID SIGNAL-REGULATED KINASE; PRIMARY AFFERENT NEURONS; PRIMARY SENSORY NEURONS; DORSAL-HORN NEURONS; PROTEIN-KINASE; GLIAL ACTIVATION; MAP KINASE; RAT MODEL; PERIPHERAL NEUROPATHY; CENTRAL SENSITIZATION AB Activation of extracellular signal-regulated kinase (ERK), a mitogen activated-protein kinase (MAPK), in dorsal horn neurons contributes to inflammatory pain by transcription-dependent and -independent means. We have now investigated if ERK is activated in the spinal cord after a spinal nerve ligation (SNL) and if this contributes to the neuropathic pain-like behavior generated in this model. An L5 SNL induces an immediate (< 10 min) but transient (< 6 h) induction of phosphoERK (pERK) restricted to neurons in the superficial dorsal horn. This is followed by a widespread induction of pERK in spinal microglia that peaks between I and 3 days post-surgery. On Day 10, pERK is expressed both in astrocytes and microglia, but by Day 21 predominantly in astrocytes in the dorsal horn. In the L5 DRG SNL transiently induces pERK in neurons at 10 min, and in satellite cells on Day 10 and 21. Intrathecal injection of the MEK (ERK kinase) inhibitor PD98059 on Day 2, 10 or 21 reduces SNL-induced mechanical allodynia. Our results suggest that ERK activation in the dorsal horn, as well as in the DRG, mediates pain through different mechanisms operating in different cells at different times. The sequential activation of ERK in dorsal horn microglia and then in astrocytes might reflect distinct roles for these two subtypes of glia in the temporal evolution of neuropathic pain. (c) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Brigham & Womens Hosp, Pain Res Ctr, Dept Anesthesiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ji, RR (reprint author), Brigham & Womens Hosp, Pain Res Ctr, Dept Anesthesiol, 75 Francis St,Med Res Bldg,Room 604, Boston, MA 02115 USA. EM rrji@zeus.bwh.harvard.edu OI Ji, Ru-Rong/0000-0002-9355-3688 FU FIC NIH HHS [R03 TW007180]; NINDS NIH HHS [NS038253, R01 NS040698, R01NS 40698] NR 64 TC 422 Z9 463 U1 7 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2005 VL 114 IS 1-2 BP 149 EP 159 DI 10.1016/j.pain.2004.12.022 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 906ZI UT WOS:000227683500017 PM 15733640 ER PT J AU Shifrin, AL Chirmule, N Gao, GP Wilson, JM Raper, SE AF Shifrin, AL Chirmule, N Gao, GP Wilson, JM Raper, SE TI Innate immune responses to adenoviral vector-mediated acute pancreatitis SO PANCREAS LA English DT Article DE rodent; adenoviral vector; macrophages; natural killer cells; natural killer T lymphocytes; interleukin-6; interleukin-10; interleukin-12 ID GENE-TRANSFER; RECOMBINANT ADENOVIRUS; MOUSE-LIVER; EXPRESSION; CELLS; INFECTION; MACROPHAGES; IMMUNODEFICIENCY; STRATEGIES; CYTOLYSIS AB Objectives: The role of innate immunity in the development of acute viral pancreatitis is not well understood. The aim of the study was to characterize the role of the innate immune system, especially macrophages, natural killer (NK), and NK T (NKT) cells, in the generation of immune responses to intrapancreatic delivery of recombinant adenoviral vector. Methods: Adenoviral vectors expressing beta-galactosidase or green fluorescent protein genes with viral capsid conjugated covalently with carbocyanine dye were directly injected into the pancreas of C57Bl/6 mice. Results: Fluorescent microscopy of the pancreas showed that 30 minutes after vector administration, adenoviral particles localized to cell membranes, internalized, and localized to the nucleus by 4 hours, and transgene expression began at 24 hours. Immunohistochemical staining showed macrophages entering the pancreas shortly after vector administration, with maximal infiltration at day 4, and then disappearing as antigen-expressing cells were eliminated. Intrapancreatic macrophages appeared to deliver viral capsid proteins to the spleen. Flow cytometry showed that NK and NKT cells migrate to the pancreas and persist. Serum cytokines IL-6, IL-10, and IL-12 were all elevated. Conclusion: Macrophages and NK and NKT cells play a major role in the development of acute adenovirus-mediated pancreatitis. C1 Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Merck & Co Inc, Wayne, PA USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Raper, SE (reprint author), Univ Penn, Sch Med, Dept Surg, 4 Silverstein Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM rapers@uphs.upenn.edu RI Wilson, James/F-9220-2011 OI Wilson, James/0000-0002-9630-3131 FU NIDDK NIH HHS [DK47787, DK54208] NR 42 TC 11 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2005 VL 30 IS 2 BP 122 EP 129 DI 10.1097/01.mpa.0000151578.99413.88 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 903DH UT WOS:000227405200005 PM 15714134 ER PT J AU Zacharia, TT Jaramillo, D Poussaint, TY Korf, B AF Zacharia, TT Jaramillo, D Poussaint, TY Korf, B TI MR imaging of abdominopelvic involvement in neurofibromatosis type 1: a review of 43 patients SO PEDIATRIC RADIOLOGY LA English DT Article DE neurofibromatosis type I; plexiform neurofibromas; abdominopelvic lesions; MR ID VONRECKLINGHAUSEN NEUROFIBROMATOSIS; PLEXIFORM NEUROFIBROMAS; CT AB Background: Plexiform neurofibromas are a frequent complication of neurofibromatosis type 1. This article discusses MR imaging findings and distribution of plexiform neurofibromas in the abdomen and pelvis. Objective: To define the most prevalent patterns of involvement and MR imaging findings in abdominopelvic neurofibromatosis type 1. Materials and methods: We reviewed the MR appearance of abdominopelvic lesions in 23 male and 20 female patients (median age: 16 years) with type 1 neurofibromatosis. The patients were part of a multi-institutional study of 300 patients. Imaging included coronal or sagittal, and axial short tau inversion recovery images. Results: The most common abdominopelvic involvement was in the abdominopelvic wall (n=28, 65%) and lumbosacral plexus (n=27, 63%). Retroperitoneal involvement was frequent (n=15, 35%). Lesions were less often intraperitoneal (21%) (P=0.001). Pelvic disease (n=27, 63%), neural canal involvement (n=18, 42%), and hydronephrosis (n=4, 9%) were also noted. Target-like appearance of plexiform lesions was noted in more than half the patients. Conclusion: Abdominopelvic involvement in neurofibromatosis type 1 is primarily extraperitoneal. Although lesions are most prevalent in the abdominopelvic wall and lumbosacral plexus, retroperitoneal and pelvic involvement is common and usually affects important organs. MR imaging added information in the initial and follow-up clinical evaluation of these patients. C1 Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Univ Alabama Birmingham Hosp, Dept Genet, Birmingham, AL USA. RP Jaramillo, D (reprint author), Childrens Hosp Philadelphia, Dept Radiol, 34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM Jaramillo@E-mail.chop.edu OI Zacharia, Thomas/0000-0002-6908-9440 NR 16 TC 11 Z9 13 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD MAR PY 2005 VL 35 IS 3 BP 317 EP 322 DI 10.1007/s00247-004-1352-z PG 6 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 905FE UT WOS:000227552700014 PM 15517232 ER PT J AU Winickoff, JP Berkowitz, AB Brooks, K Tanski, SE Geller, A Thomson, C Lando, HA Curry, S Muramoto, M Prokhorov, AV Best, D Weitzman, M Pbert, L AF Winickoff, JP Berkowitz, AB Brooks, K Tanski, SE Geller, A Thomson, C Lando, HA Curry, S Muramoto, M Prokhorov, AV Best, D Weitzman, M Pbert, L CA Amer Acad Pediat TI State-of-the-art interventions for office-based parental tobacco control SO PEDIATRICS LA English DT Review DE tobacco; smoking; adolescent; child; parent; pediatrician; nicotine-replacement therapy; NRT; nicotine; tobacco dependence; guideline; clinical practice guideline; environmental tobacco smoke; secondhand smoke; SHS ID SMOKING-CESSATION INTERVENTION; RECEIVING GENERAL-ANESTHESIA; RANDOMIZED CONTROLLED-TRIAL; ADVERSE RESPIRATORY EVENTS; MATERNAL SMOKING; PASSIVE SMOKING; ADOLESCENT SMOKING; UNITED-STATES; LOW-INCOME; ASTHMATIC-CHILDREN AB Parental tobacco use is a serious health issue for all family members. Child health care clinicians are in a unique and important position to address parental smoking because of the regular, multiple contacts with parents and the harmful health consequences to their patients. This article synthesizes the current evidence-based interventions for treatment of adults and applies them to the problem of addressing parental smoking in the context of the child health care setting. Brief interventions are effective, and complementary strategies such as quitlines will improve the chances of parental smoking cessation. Adopting the 5 A's framework strategy ( ask, advise, assess, assist, and arrange) gives each parent the maximum chance of quitting. Within this framework, specific recommendations are made for child health care settings and clinicians. Ongoing research will help determine how best to implement parental smoking-cessation strategies more widely in a variety of child health care settings. C1 MGH Ctr Child & Adolescent Hlth Policy, Div Gen Pediat, MassGen Hosp Children, Boston, MA USA. Tobacco Res & Treatment Ctr, Boston, MA USA. Boston Univ, Sch Med, Dept Dermatol, Canc Control Ctr, Boston, MA 02118 USA. Univ Rochester, Strong Childrens Res Ctr, Rochester, NY USA. Boston Univ, Sch Med, Dept Dermatol, Canc Control Ctr, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, MGH Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Illinois, Hlth Res & Policy Ctr, Chicago, IL USA. Univ Arizona, Hlth Sci Ctr, Dept Family & Community Med, Tucson, AZ USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA. Univ Rochester, Ctr Child Hlth Res, Rochester, NY USA. Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA USA. RP Winickoff, JP (reprint author), MGH Ctr Child & Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jwinickoff@partners.org FU NCI NIH HHS [1 K07 CA100213 A 01] NR 140 TC 61 Z9 61 U1 5 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 2005 VL 115 IS 3 BP 750 EP 760 DI 10.1542/peds.2004-1055 PG 11 WC Pediatrics SC Pediatrics GA 905UV UT WOS:000227596900037 PM 15741382 ER PT J AU Yovel, I Mineka, S AF Yovel, I Mineka, S TI Emotion-congruent attentional biases: the perspective of hierarchical models of emotional disorders SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE models; anxiety; selective attention; cognitive processes ID TRIPARTITE MODEL; MOOD DISORDERS; ANXIETY; DEPRESSION; INFORMATION; AWARENESS; DIMENSIONS; THREAT; STROOP AB Using the rationale of current hierarchical models of anxiety and depression, this study examined relationships between common and specific factors of these syndromes and emotion-congruent attentional biases, Participants (n = 72) performed an emotional Stroop task, in which anxiety- and depression-related as well as neutral non-valenced words were presented both supra- and subliminally. The anxiety-related general distress scale, but not specific anxiety scales, correlated significantly with the anxiety-related subliminal bias. A partial correlational analysis showed that this relationship was independent of scores on depression-related scales. In agreement with most previous findings, no depression-related attentional biases were found. As expected for sub-clinical populations none of the scales was associated with any supraliminal attentional bias. (C) 2004 Elsevier Ltd. All rights reserved. C1 Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA. RP Yovel, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM iyovel@partners.org NR 35 TC 38 Z9 48 U1 7 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD MAR PY 2005 VL 38 IS 4 BP 785 EP 795 DI 10.1016/j.paid.2004.06.003 PG 11 WC Psychology, Social SC Psychology GA 895WC UT WOS:000226893700004 ER PT J AU Lewis, MA Butterfield, RM AF Lewis, MA Butterfield, RM TI Antecedents and reactions to health-related social control SO PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN LA English DT Article DE social control; health behaviors; emotions ID POWER STRATEGIES; PSYCHOLOGICAL DISTRESS; LIFE STRESS; BEHAVIORS; SUPPORT; INTEGRATION; MARRIAGE; GENDER AB A model of the antecedents and reactions to health-related social control is proposed. This model suggests health behavior characteristics, including type, frequency, and severity of consequences, are social control antecedents. Social control is then thought to elicit better health behavior and emotions. Attributions to explain social control are proposed to effect emotional reactions and behavior. Undergraduates read hypothetical scenarios to test the proposed model. Study 1 found that health compromising behaviors and behaviors with more severe consequences elicited more social control. Study 2 found that, compared to negative tactics, positive social control tactics elicited more behavior change, and compared to social appearance concerns, attributions to health elicited positive emotions. Attributions did not moderate the impact of social control on emotions or behavior. C1 Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lewis, MA (reprint author), Univ N Carolina, Sch Publ Hlth, CB 7440, Chapel Hill, NC 27599 USA. EM megan.lewis@unc.edu FU NIMH NIH HHS [MH52313] NR 46 TC 43 Z9 43 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0146-1672 J9 PERS SOC PSYCHOL B JI Pers. Soc. Psychol. Bull. PD MAR PY 2005 VL 31 IS 3 BP 416 EP 427 DI 10.1177/0146167204271600 PG 12 WC Psychology, Social SC Psychology GA 894MU UT WOS:000226796800011 PM 15657456 ER PT J AU Xu, K Bastia, E Schwarzschild, M AF Xu, K Bastia, E Schwarzschild, M TI Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE adenosine A(2A) receptor; caffeine; dyskinesia; neuroprotection; Parkinson's disease; striatum ID C-FOS EXPRESSION; MESSENGER-RNA EXPRESSION; DOPAMINE-DENERVATED RATS; CENTRAL-NERVOUS-SYSTEM; STRIATAL GLUTAMATE OUTFLOW; GABAERGIC SYNAPTIC-TRANSMISSION; LEVODOPA-INDUCED DYSKINESIA; ENVIRONMENTAL RISK-FACTORS; INDUCED MOTOR ALTERATIONS; POSTMORTEM HUMAN BRAIN AB In the pursuit of improved treatments for Parkinson's disease (PD), the adenosine A(2A) receptor has emerged as an attractive nondopaminergic target. Based on the compelling behavioral pharmacology and selective basal ganglia expression of this G-protein-coupled receptor, its antagonists are now crossing the threshold of clinical development as adjunctive symptomatic treatment for relatively advanced PD. The antiparkinsonian potential of A(2A) antagonism has been boosted further by recent preclinical evidence that A(2A) antagonists might favorably alter the course as well as the symptoms of the disease. Convergent epidemiological and laboratory data have suggested that A(2A) blockade may confer neuroprotection against the underlying dopaminergic neuron degeneration. In addition, rodent and nonhuman primate studies have raised the possibility that A(2A) receptor activation contributes to the pathophysiology of dyskinesias-problematic motor complications of standard PD therapy-and that A(2A) antagonism might help prevent them. Realistically, despite being targeted to basal ganglia pathophysiology, A(2A) antagonists may be expected to have other beneficial and adverse effects elsewhere in the central nervous system (e.g., on mood and sleep) and in the periphery (e.g., on immune and inflammatory processes). The thoughtful design of new clinical trials of A(2A) antagonists should take into consideration these counterbalancing hopes and concerns and may do well to shift toward a broader set of disease-modifying as well as symptomatic indications in early PD. (c) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Schwarzschild, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM michaels@helix.mgh.harvard.edu FU NIDA NIH HHS [DA13508]; NIEHS NIH HHS [ES10804] NR 428 TC 151 Z9 157 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAR PY 2005 VL 105 IS 3 BP 267 EP 310 DI 10.1016/j.pharmthera.2004.10.007 PG 44 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 906PM UT WOS:000227654200003 PM 15737407 ER PT J AU Thompson, AN Osgood, TS AF Thompson, AN Osgood, TS TI Doctor of pharmacy student impact on patient care in the critical care units. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Spring Practice and Research Forum of the American-College-of-Clinical-Pharmacy CY APR 10-13, 2005 CL Myrtle Beach, SC SP Amer Coll Clin Pharm C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 2005 VL 25 IS 3 MA 155 BP 477 EP 477 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 901NJ UT WOS:000227288900136 ER PT J AU Castano, AP Demidova, TN Hamblin, MR AF Castano, Ana P. Demidova, Tatiana N. Hamblin, Michael R. TI Mechanisms in photodynamic therapy: part two-cellular signaling, cell metabolism and modes of cell death SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY LA English DT Review DE Photodynamic therapy; Signal transduction; Lipid metabolism; Apoptosis; Necrosis; Reactive oxygen species; Stress response; Cell adhesion AB Photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its most successful applications are for non-malignant disease. In the second of a series of three reviews, we will discuss the mechanisms that operate in PDT on a cellular level. In Part I [Castano AP, Demidova TN, Hamblin MR. Mechanism in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther 2004;1:279-93] it was shown that one of the most important factors governing the outcome of PDT, is how the photosensitizer (PS) interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS. PS can localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes. An explosion of investigation and explorations in the field of cell biology have elucidated many of the pathways that mammalian cells undergo when PS are delivered in tissue culture and subsequently illuminated. There is an acute stress response leading to changes in calcium and lipid metabolism and production of cytokines and stress proteins. Enzymes particularly, protein kinases, are activated and transcription factors are expressed. Many of the cellular responses are centered on mitochondria. These effects frequently lead to induction of apoptosis either by the mitochondrial pathway involving caspases and release of cytochrome c, or by pathways involving ceramide or death receptors. However, under certain circumstances cells subjected to PDT die by necrosis. Although there have been many reports of DNA damage caused by PDT, this is not thought to be an important cell-death pathway. This mechanistic research is expected to lead to optimization of PDT as a tumor treatment, and to rational selection of combination therapies that include PDT as a component. (C) 2005 Elsevier B.V. All rights reserved. C1 [Castano, Ana P.; Demidova, Tatiana N.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR314B, Boston, MA 02114 USA. [Castano, Ana P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Demidova, Tatiana N.] Tufts Univ, Dept Cellular Mol & Dev Biol, Medford, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR314B, 50 Blossom St,Bartlett 3, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Department of Defense CDMRP Breast Cancer Research Grant; Wellman Center of Photomedicine graduate student fellowship; US National Institutes of Health [R01-CA/AI838801] FX Ana P. Castano was supported by a Department of Defense CDMRP Breast Cancer Research Grant. Tatiana N. Demidova was supported by a Wellman Center of Photomedicine graduate student fellowship. Michael R. Hamblin was supported by the US National Institutes of Health (R01-CA/AI838801). We are grateful to Anna Yaroslavsky and Tayyaba Hasan for help and support. NR 188 TC 234 Z9 245 U1 12 U2 71 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-1000 J9 PHOTODIAGN PHOTODYN JI Photodiagnosis Photodyn. Ther. PD MAR PY 2005 VL 2 IS 1 BP 1 EP 23 DI 10.1016/S1572-1000(05)00030-X PG 23 WC Oncology SC Oncology GA V27CH UT WOS:000208590800001 PM 25048553 ER PT J AU Ripoll, J Ntziachristos, V AF Ripoll, J Ntziachristos, V TI Quantitative point source photoacoustic inversion formulas for scattering and absorbing media SO PHYSICAL REVIEW E LA English DT Article ID IN-VIVO; TOMOGRAPHY; RECONSTRUCTION; TISSUE; WAVES AB We present here an expression for the photoacoustic contribution of an optical point source in a diffusive and absorbing medium. By using this measurement as a reference, we present a direct inversion formula that recovers the absorption map quantitatively, at the same time accounting for instrumental factors such as the source strength, the shape of the optical pulse, and the impulse response and finite size of the transducers. We further validate this expression through accurate numerical simulations showing that the absorption map is recovered quantitatively in the presence of a rotating geometry. We finally discuss how the presented solutions for point sources within the photoacoustic problem enable the use of concurrent fluorescence and ultrasound measurements as appropriate for a hybrid tomographic system. The proposed system could retrieve absorption information using photoacoustic measurements, and use these data to more accurately describe the fluorescence problem and improve reconstruction fidelity. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. RP Ripoll, J (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, Iraklion 71110, Greece. EM jripoll@iesl.forth.gr; vasilis@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R33-CA91807]; NIBIB NIH HHS [R01 EB000750-1] NR 21 TC 52 Z9 52 U1 0 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD MAR PY 2005 VL 71 IS 3 AR 031912 DI 10.1103/PhysRevE.71.031912 PN 1 PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 919PM UT WOS:000228630000070 PM 15903464 ER PT J AU Tze, LE Schram, BR Lam, KP Hogquist, KA Hippen, KL Liu, J Shinton, SA Otipoby, KL Rodine, PR Vegoe, AL Kraus, M Hardy, RR Schlissel, MS Rajewsky, K Behrens, TW AF Tze, LE Schram, BR Lam, KP Hogquist, KA Hippen, KL Liu, J Shinton, SA Otipoby, KL Rodine, PR Vegoe, AL Kraus, M Hardy, RR Schlissel, MS Rajewsky, K Behrens, TW TI Basal immunoglobulin signaling actively maintains developmental stage in immature B cells SO PLOS BIOLOGY LA English DT Article ID ALLELIC EXCLUSION; ANTIGEN RECEPTOR; IG-BETA; T-CELL; CYTOPLASMIC DOMAINS; V(D)J RECOMBINATION; ANTIBODY REPERTOIRE; CLONAL SELECTION; GENE-EXPRESSION; TRANSGENIC MICE AB In developing B lymphocytes, a successful V( D) J heavy chain ( HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking "back-differentiation'' of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms. C1 Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Behrens, TW (reprint author), Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. EM behre001@umn.edu RI ASTAR, IMCB/E-2320-2012; Lam, Kong-Peng/G-5374-2012; OI Lam, Kong-Peng/0000-0002-1316-4333; Hogquist, Kristin/0000-0001-9963-5687 NR 52 TC 90 Z9 90 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD MAR PY 2005 VL 3 IS 3 BP 463 EP 475 AR e82 DI 10.1371/journal.pbio.0030082 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 911ED UT WOS:000227984000014 PM 15752064 ER PT J AU Clark, J Cools, J Gilliland, DG AF Clark, J Cools, J Gilliland, DG TI EGFR inhibition in non-small cell lung cancer: Resistance, once again, rears its ugly head SO PLOS MEDICINE LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMOR; TYROSINE KINASE; BCR-ABL; ACQUIRED-RESISTANCE; BLAST CRISIS; IMATINIB; GEFITINIB; THERAPY; MUTATIONS; LEUKEMIA C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu OI Cools, Jan/0000-0001-6626-5843 NR 18 TC 13 Z9 14 U1 3 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAR PY 2005 VL 2 IS 3 BP 195 EP 197 AR e75 DI 10.1371/journal.pmed.0020075 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 916JZ UT WOS:000228382500007 PM 15736989 ER PT J AU Gupta, V Carey, JL Kawakubo, H Muzikansky, A Green, JE Donahoe, PK MacLaughlin, DT Maheswaran, S AF Gupta, V Carey, JL Kawakubo, H Muzikansky, A Green, JE Donahoe, PK MacLaughlin, DT Maheswaran, S TI Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen transgenic mouse mammary carcinoma model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE proliferation; apoptosis; simian virus 40 large T antigen ID CANCER CELL-GROWTH; IN-VIVO; BREAST-CANCER; SEXUAL DEVELOPMENT; GENE-EXPRESSION; II RECEPTOR; T-ANTIGEN; HORMONE; PATHWAY; REGRESSION AB Mullerian inhibiting substance (MIS) inhibits breast cancer cell growth in vitro. To extend the use of MIS to treat breast cancer, it is essential to test the responsiveness of mammary tumor growth to MIS in vivo. Mammary tumors arising in the C3(1) T antigen mouse model expressed the MIS type II receptor, and MIS in vitro inhibited the growth of cells derived from tumors. Administration of MIS to mice was associated with a lower number of palpable mammary tumors compared with vehicle-treated mice (P = 0.048), and the mean mammary tumor weight in the MIS-treated group was significantly lower compared with the control group (P = 0.029). Analysis of proliferating cell nuclear antigen (PCNA) expression and caspase-3 cleavage in tumors revealed that exposure to MIS was associated with decreased proliferation and increased apoptosis, respectively, and was not caused by a decline in T antigen expression. The effect of MIS on tumor growth was also evaluated on xenografted human breast cancer cell line MDA-MB-468, which is estrogen receptor- and retinoblastoma-negative and expresses mutant p53, and thus complements the C3(1)Tag mouse mammary tumors that do not express estrogen receptor and have functional inactivation of retinoblastoma and p53. In agreement with results observed in the transgenic mice, MIS decreased the rate of MDA-MB-468 tumor growth and the gain in mean tumor volume in severe combined immunodeficient mice compared' with vehicle-treated controls (P = 0.004). These results suggest that MIS can suppress the growth of mammary tumors in vivo. C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. EM maheswaran@helix.mgh.harvard.edu FU NCI NIH HHS [CA089138-04, R01 CA089138, R01 CA017393, CA17393]; NICHD NIH HHS [HD32112, R01 HD032112] NR 30 TC 20 Z9 22 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 MAR 1 PY 2005 VL 102 IS 9 BP 3219 EP 3224 DI 10.1073/pnas.0409709102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903KC UT WOS:000227423700012 PM 15728372 ER PT J AU Song, G Yang, YT Liu, JH Casasnovas, JM Shimaoka, M Springer, TA Wang, JH AF Song, G Yang, YT Liu, JH Casasnovas, JM Shimaoka, M Springer, TA Wang, JH TI An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin alpha(L)beta(2) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE structure; protein recognition; cell adhesion; LFA-1 ID INTERCELLULAR-ADHESION MOLECULE-1; FUNCTION-ASSOCIATED ANTIGEN-1; CELL-ADHESION; I-DOMAIN; COUNTER-RECEPTOR; T-LYMPHOCYTES; CRYSTAL-STRUCTURE; LFA-1; RESIDUES; RHINOVIRUS AB Within the Ig superfamily (IgSF), intercellular adhesion molecules (ICAMs) form a subfamily that binds the leukocyte integrin alpha(L)beta(2). We report a 1.65-Angstrom-resolution crystal structure of the ICAM-3 N-terminal domain (D1) in complex with the inserted domain, the ligand-binding domain of alpha(L)beta(2). This high-resolution structure and comparisons among ICAM subfamily members establish that the binding of ICAM-3 D1 onto the inserted domain represents a common docking mode for ICAM subfamily members. The markedly different off-rates of ICAM-1, -2, and -3 appear to be determined by the hydrophobicity of residues that surround a metal coordination bond in the alpha(L)beta(2)-binding interfaces. Variation in composition of glycans on the periphery of the interfaces influences on-rate. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. EM springer@cbr.med.harvard.edu; jwang@red.dfci.harvard.edu RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798]; NHLBI NIH HHS [HL48675, P01 HL048675] NR 45 TC 45 Z9 46 U1 1 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 MAR 1 PY 2005 VL 102 IS 9 BP 3366 EP 3371 DI 10.1073/pnas.0500200102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903KC UT WOS:000227423700037 PM 15728350 ER PT J AU Zile, MR Baicu, CF Bonnema, DD AF Zile, MR Baicu, CF Bonnema, DD TI Diastolic heart failure: Definitions and terminology SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID VENTRICULAR EJECTION FRACTION; SYSTOLIC DYSFUNCTION; THERAPEUTIC OPTIONS; PART II; ABNORMALITIES; MECHANISMS; MORTALITY; EXERCISE C1 Med Univ S Carolina, Div Cardiol, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Zile, MR (reprint author), Med Univ S Carolina, Div Cardiol, Dept Med, 135 Rutledge Ave,Suite 1201,POB 250592, Charleston, SC 29425 USA. EM zilem@musc.edu FU NHLBI NIH HHS [P01-HL-48788] NR 39 TC 29 Z9 33 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAR-APR PY 2005 VL 47 IS 5 BP 307 EP 313 DI 10.1016/j.pcad.2005.02.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 949IK UT WOS:000230778300001 PM 16003645 ER PT J AU Westra, SJ Wallace, EC AF Westra, SJ Wallace, EC TI Imaging evaluation of pediatric chest trauma SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID COMPUTED-TOMOGRAPHY; DIAPHRAGMATIC INJURIES; THORACIC INJURY; CT FINDINGS; HELICAL CT; CHILDREN; RADIATION; DIAGNOSIS; PULMONARY; POPULATION AB Following a discussion of the various imaging manifestations of pediatric chest trauma by anatomic location, the authors discuss their diagnostic approach to the pediatric multi-trauma patient with an emphasis on chest imaging. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Div Pediat Radiol, Worcester, MA USA. RP Westra, SJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 34 Fruit St, Boston, MA 02114 USA. EM swestra@partners.org NR 51 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2005 VL 43 IS 2 BP 267 EP + DI 10.1016/j.rcl.2004.11.003 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 908TJ UT WOS:000227812800003 PM 15737369 ER PT J AU Sahani, DV Kalva, SP Hamberg, LM Hahn, PF Willett, CG Saini, S Mueller, PR Lee, TY AF Sahani, DV Kalva, SP Hamberg, LM Hahn, PF Willett, CG Saini, S Mueller, PR Lee, TY TI Assessing tumor perfusion and treatment response in rectal cancer with multisection CT: Initial observations SO RADIOLOGY LA English DT Article; Proceedings Paper CT 89th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 30-DEC 05, 2003 CL CHICAGO, IL SP Radiol Soc N Amer ID DYNAMIC COMPUTED-TOMOGRAPHY; BLOOD-FLOW; CONTRAST ENHANCEMENT; COLORECTAL-CANCER; VASCULAR DENSITY; HELICAL CT; ANGIOGENESIS; CARCINOMA; TISSUE; THERAPY AB PURPOSE: To use first-pass perfusion computed tomography (CT) to prospectively investigate tumor vascularity in rectal cancer and to determine whether any of the perfusion parameters would predict tumor response to chemotherapy and radiation therapy. MATERIALS AND METHODS: The institutional review board approved this study, and informed prior consent was obtained from participants. Perfusion CT of rectal cancer was performed with four-section multi-detector row CT in 15 patients (13 men, two women; mean age, 62.1 years; age range, 46-84 years). Five patients with prostate cancer served as controls. All patients with rectal cancer underwent 6-8 weeks of chemotherapy and radiation therapy followed by surgery. In nine patients, perfusion CT was repeated after completion of chemotherapy and radiation therapy. Contrast medium-enhanced dynamic CT was performed with a static table position for 45 seconds, and the data were analyzed by using commercial software to calculate tissue blood flow (BF), blood volume, mean transit time (MTT), and vascular permeability-surface area product. Perfusion parameters of normal rectum and tumor were compared. Perfusion parameters before and after chemotherapy and radiation therapy were compared. A tumor was considered to have responded if its stage at pathologic analysis indicated regression compared with the preoperative stage. Baseline perfusion values were compared between responders and nonresponders. Statistical analysis was performed with the Student t test. RESULTS: Rectal cancer showed higher BF and shorter MTT compared with those of normal rectum (P less than or equal to .05). After chemotherapy and radiation therapy, tumors showed significant reduction in BF and increase in MTT (P less than or equal to .05). There was a significant difference in baseline BF and MTT values between responders and nonresponders (P less than or equal to .05). Tumors in three patients with high initial BF and short MTT showed poor response. CONCLUSION: Perfusion CT of rectal cancer can enable assessment of tumor vascularity and perfusion changes that result from chemotherapy and radiation therapy. In this small patient sample, tumors with initial high BF and short MTT values tended to respond poorly to chemotherapy and radiation therapy. (C) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270 F, Boston, MA 02114 USA. EM dsahani@partners.org NR 46 TC 172 Z9 199 U1 0 U2 1 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 MAR PY 2005 VL 234 IS 3 BP 785 EP 792 DI 10.1148/radiol.2343040286 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 899LM UT WOS:000227145900018 PM 15734934 ER PT J AU Cohen, SP Larkin, TM Barna, SA Palmer, WE Hecht, AC Stojanovic, MP AF Cohen, SP Larkin, TM Barna, SA Palmer, WE Hecht, AC Stojanovic, MP TI Lumbar discography: A comprehensive review of outcome studies, diagnostic accuracy, and principles SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Review DE degenerative disc disease; discogenic pain; discography; internal disc disruption; intervertebral disc; lumbar spine ID LOW-BACK-PAIN; ARTIFICIAL DISC REPLACEMENT; INTRADISCAL ELECTROTHERMAL TREATMENT; PREVIOUSLY ASYMPTOMATIC SUBJECTS; HIGH-INTENSITY ZONE; MINIMUM FOLLOW-UP; INTERVERTEBRAL DISCS; NUCLEUS PULPOSUS; PROVOCATIVE DISCOGRAPHY; PROPHYLACTIC ANTIBIOTICS AB Background and Objectives: Since its advent more than 50 years ago, the use of discography has been mired in controversy. The purpose of this review is to provide a clinical overview of lumbar discography and discogenic back pain, with special emphasis on determining the accuracy of discography and whether or not the procedure improves outcomes for surgery. Methods: Material for this review was obtained from a MEDLINE search conducted from 1951 thru September 2004, bibliographic references, book chapters, and conference proceedings. Results: Based on a large number of comparative studies, plain discography is less accurate than magnetic resonance imaging in diagnosing lumbar herniated nucleus pulposus and comparable or slightly more sensitive in detecting degenerative disc disease. For disc degeneration, CT discography remains the gold standard for diagnosis. There are very few studies comparing surgical outcomes between patients who have undergone preoperative provocative discography and those who have not. What little evidence exists is conflicting. Before disc replacement surgery, approximately half the studies have used preoperative discography. A comparison of outcomes did not reveal any significant difference between the 2 groups but none of the studies was controlled, and they used different outcome measures, follow-up periods, and surgical techniques. Because all intradiscal electrothermal therapy (IDET) studies have used discography before surgery, no conclusions can be drawn regarding its effects on outcome. Conclusions: Although discography, especially combined with CT scanning, may be more accurate than other radiologic studies in detecting degenerative disc disease, its ability to improve surgical outcomes has yet to be proven. In the United States and Europe, there are inconsistencies in the use of lumbar discography such that it is routinely used before IDET, yet only occasionally used before spinal fusion. C1 Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Pain Management Ctr, Baltimore, MD 21205 USA. Walter Reed Army Med Ctr, Pain Management Ctr, Washington, DC 20307 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Pain Ctr, Boston, MA 02115 USA. Walter Reed Army Med Ctr, Dept Anesthesiol, Washington, DC 20307 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Orthoped Surg, New York, NY USA. RP Cohen, SP (reprint author), Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Pain Management Ctr, 550 N Broadway,Suite 301, Baltimore, MD 21205 USA. EM scohen40@jhmi.edu NR 150 TC 49 Z9 52 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAR-APR PY 2005 VL 30 IS 2 BP 163 EP 183 DI 10.1016/j.rapm.2004.10.006 PG 21 WC Anesthesiology SC Anesthesiology GA 908OJ UT WOS:000227796100008 PM 15765459 ER PT J AU Grimm, J Wunder, A AF Grimm, J Wunder, A TI Current state of molecular imaging research SO ROFO-FORTSCHRITTE AUF DEM GEBIET DER RONTGENSTRAHLEN UND DER BILDGEBENDEN VERFAHREN LA German DT Review DE targeted contrast agents; CT; MRT; nuclear medicine; optical imaging; ultrasound ID REPORTER GENE-EXPRESSION; IN-VIVO; CONTRAST ULTRASOUND; LIVING SUBJECTS; TRACKING; PROBES; TUMORS; MICE; VISUALIZATION; MICROBUBBLES AB The recent years have seen significant advances in both molecular biology, allowing the identification of genes and pathways related to disease, and imaging technologies that allow for improved spatial and temporal resolution, enhanced sensitivity, better depth penetration, improved image processing, and beneficial combinations of different imaging modalities. These advances have led to a paradigm shift in the scope of diagnostic imaging. The traditional role of radiological diagnostic imaging is to define gross anatomy and structure in order to detect pathological abnormalities. Available contrast agents are mostly nonspecific and can be used to image physiological processes such as changes in blood volume, flow, and perfusion but not to demonstrate pathological alterations at molecular levels. However, alterations at the anatomical-morphological level are relatively late manifestations of underlying molecular changes. Using molecular probes or markers that bind specifically to molecular targets allows for the non-invasive visualization and quantitation of biological processes such as gene expression, apoptosis, or angiogenesis at the molecular level within intact living organisms. This rapidly evolving, multidisciplinary approach, referred to as molecular imaging, promises to enable early diagnosis, can provide improved classification of stage and severity of disease, an objective assessment of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes, and for the development of new therapies. This article comprises a review of current technologies of molecular imaging, describes the development of contrast agents and various imaging modalities, new applications in specific disease models, and potential future developments. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, CMIIR, Charlestown, MA USA. Univ Klinikum Schleswig Holstein, Radiol Diagnost Klin, Kiel, Germany. RP Wunder, A (reprint author), Univ Regensburg, Klin & Poliklin Innere Med 1, Bereich Rheumatol Klin Immunol, ZMB, Josef Engert Str 9, D-93053 Regensburg, Germany. EM andreas.wunder@klinik.uni-regensburg.de RI Grimm, Jan/B-1937-2008 NR 61 TC 14 Z9 15 U1 0 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 1438-9029 J9 ROFO-FORTSCHR RONTG JI Rofo-Fortschr. Gebiet Rontgenstrahlen Bildgeb. Verfahr. PD MAR PY 2005 VL 177 IS 3 BP 326 EP 337 DI 10.1055/s-2005-857946 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 903BV UT WOS:000227401300004 PM 15719293 ER PT J AU Hennen, J Baldessarini, RJ AF Hennen, J Baldessarini, RJ TI Suicidal risk during treatment with clozapine: a meta-analysis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE antipsychotics; clozapine; meta-analysis; schizophrenia; suicidal behavior ID BIPOLAR DISORDER; RESISTANT SCHIZOPHRENIA; CLINICAL-TRIALS; FOLLOW-UP; MORTALITY; PREVENTION; LITHIUM; IMPACT; REDUCTION; BEHAVIOR AB Objective: Suicide remains a major cause of premature mortality among patients with schizophrenia. Evidence of reduced suicidal risk with available psychiatric treatments is limited, but emerging data suggest such an effect of clozapine in chronically psychotic patients, leading us to compile the reported evidence. Method: We searched for published studies with contrasting rates of suicides or attempts by psychotic patients treated with clozapine vs. other agents. Results: Among six such studies, random-effects meta-analysis indicated a substantially lower overall risk of suicidal behaviors with clozapine vs. other treatments (risk-ratio 3.3; 95% confidence interval [CI] 1.7-6.3; p<0.000 1). For completed suicides, the risk ratio (RR) was 2.9 ([CI 1.5-5.7]; p=0.002). Conclusion: Long-term treatment with clozapine was associated with three-fold overall reduction of risk of suicidal behaviors. However, available findings are quantitatively inconsistent, well-designed studies remain rare, and the only randomized trial did not find reduced risk of completed suicide. Additional randomized comparisons among modem treatments for psychotic disorders are required to clarify their impact on mortality. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr 306, Bipolar & Psychot Disorders Program, Belmont, MA USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org NR 42 TC 109 Z9 112 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 2005 VL 73 IS 2-3 BP 139 EP 145 DI 10.1016/j.schres.2004.05.015 PG 7 WC Psychiatry SC Psychiatry GA 892OY UT WOS:000226661100001 PM 15653256 ER PT J AU Glatt, SJ Wang, RS Yeh, YC Tsuang, MT Faraone, SV AF Glatt, SJ Wang, RS Yeh, YC Tsuang, MT Faraone, SV TI Five NOTCH4 polymorphisms show weak evidence for association with schizophrenia: evidence from meta-analyses SO SCHIZOPHRENIA RESEARCH LA English DT Article DE allelic association; chromosome 6p; major histocompatibility complex; meta-analysis schizophrenia; NOTCH4 ID GENE POLYMORPHISM; SUSCEPTIBILITY; FAMILY; POPULATION; JAPANESE; LOCUS; HAPLOTYPE; DISORDER; SAMPLE AB NOTCH4 initially received consideration as a risk gene for schizophrenia based on its location within a region on chromosome 6p that had previously shown strong evidence for genetic linkage with the illness. The initial published test for allelic association found strong evidence for involvement of this gene in schizophrenia, but subsequent studies failed to confirm this finding. Presently, we have used meta-analysis to derive a best estimate of the nature and magnitude of the associations between schizophrenia and five polymorphisms in and around the NOTCH4 gene. No significant association was detected between schizophrenia and repeat length of alleles at the (TAA)(n), (CTG)(n), or (TTAT)(n), polymorphisms, or between the disease and specific risk alleles at these polymorphisms or at the SNP1 or SNP2 polymorphisms. Heterogeneity and stronger evidence of association with the putative risk alleles of the (TAA)(n), (CTG)(n), SNP1, and SNP2 polymorphisms was observed in family-based studies than in case-control studies, suggesting that these polymorphisms may reliably influence risk for schizophrenia under certain circumstances. Since more consistent and robust associations with schizophrenia risk have been observed for haplotypes of these polymorphisms [especially those containing SNP2 and (CTG)(n)], additional large family-based or genomic-controlled studies would be helpful for definitively specifying the role of NOTCH4 haplotypes in risk for schizophrenia. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif San Diego, Inst Behav Genom, Dept Psychiat, La Jolla, CA 92093 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Dept Psychiat, Boston, MA 02115 USA. Bali Mental Hosp, Dept Gen Psychiat, Taipei, Taiwan. Dept Hlth Taiwan, Taipei, Taiwan. VA San Diego Healthcare Syst, La Jolla, CA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Glatt, SJ (reprint author), Univ Calif San Diego, Inst Behav Genom, Dept Psychiat, La Jolla, CA 92093 USA. EM sglatt@ucsd.edu OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH065562, R01MH043518, R01MH059624, R25MH060485] NR 26 TC 21 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 2005 VL 73 IS 2-3 BP 281 EP 290 DI 10.1016/j.schres.2004.07.015 PG 10 WC Psychiatry SC Psychiatry GA 892OY UT WOS:000226661100018 PM 15653273 ER PT J AU Thoma, RJ Hanlon, FM Moses, SN Ricker, D Huang, MX Edgar, C Irwin, J Torres, F Weisend, MP Adler, LE Miller, GA Canive, JM AF Thoma, RJ Hanlon, FM Moses, SN Ricker, D Huang, MX Edgar, C Irwin, J Torres, F Weisend, MP Adler, LE Miller, GA Canive, JM TI M50 sensory gating predicts negative symptoms in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; auditory sensory gating; magnetoencephalography; electroencephalography; MEG; EEG; negative symptoms ID CEREBRAL BLOOD-FLOW; P50 SUPPRESSION; PREPULSE INHIBITION; PREFRONTAL CORTEX; POSITIVE SYMPTOMS; COGNITIVE MODEL; RELIABILITY; DEFICITS; STARTLE; SCALE AB Impaired auditory sensory gating is considered characteristic of schizophrenia and a marker of the information processing deficit inherent to that disorder. Predominance of negative symptoms also reflects the degree of deficit in schizophrenia and is associated with poorer pre-morbid functioning, lower IQ, and poorer outcomes. However, a consistent relationship between auditory sensory gating and negative symptoms in schizophrenia has yet to be demonstrated. The absence of such a finding is surprising, since both impaired auditory gating and negative symptoms have been linked with impaired fronto-temporal cortical function. The present study measured auditory gating using the P50 event related potential (ERP) in a paired-click paradigm and capitalized on the relative localization advantage of magnetoencephalography (MEG) to assess auditory sensory gating in terms of the event related field (ERF) M50 source dipoles on bilateral superior temporal gyrus (STG). The primary hypothesis was that there would be a positive correlation between lateralized M50 auditory sensory gating measures and negative symptoms in patients with schizophrenia. A standard paired-click paradigm was used during simultaneous EEG and MEG data collection to determine S2/S1 sensory gating ratios in a group of 20 patients for both neuroimaging techniques. Participants were administered the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Consistent with previous reports, there was no relationship between ERP P50 sensory gating and negative symptoms. However, right (not left) hemisphere ERF M50 sensory gating ratio was significantly and positively correlated with negative symptoms. This finding is compatible with information processing theories of negative symptoms and with more recent findings of fronto-temporal abnormality in patients with predominantly negative symptoms. (C) 2004 Elsevier B.V. All rights reserved. C1 Vet Adm Med Ctr, New Mexico VA Hlth Care Syst, Psychiat Serv, Albuquerque, NM 87108 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87108 USA. Univ New Mexico, Dept Psychiat, Hlth Sci Ctr, Albuquerque, NM 87108 USA. New Mexico VA Hlth Care Syst, Dept Radiol, Albuquerque, NM 87108 USA. Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. Univ Illinois, Beckman Inst, Biomed Imaging Ctr, Urbana, IL 61801 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Psychiat Serv, Denver VAMC, Denver, CO 80202 USA. Univ Illinois, Dept Psychiat, Urbana, IL 61801 USA. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. RP Thoma, RJ (reprint author), Vet Adm Med Ctr, New Mexico VA Hlth Care Syst, Psychiat Serv, 116A,1501 San Pedro SE, Albuquerque, NM 87108 USA. EM robert.thoma@med.va.gov FU NIMH NIH HHS [1 R01 MH65304-01] NR 33 TC 52 Z9 57 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 2005 VL 73 IS 2-3 BP 311 EP 318 DI 10.1016/j.schres.2004.07.001 PG 8 WC Psychiatry SC Psychiatry GA 892OY UT WOS:000226661100021 PM 15653276 ER PT J AU Wynn, JK Sergi, MJ Dawson, ME Schell, AM Green, MF AF Wynn, JK Sergi, MJ Dawson, ME Schell, AM Green, MF TI Sensorimotor gating, orienting and social perception in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE prepulse inhibition; prepulse facilitation; social perception; schizophrenia; sensorimotor gating; social cognition ID PREPULSE INHIBITION; EMOTION RECOGNITION; STARTLE REFLEX; COGNITION; HABITUATION; DISORDER; CONTEXT; DEFICIT; MEMORY AB Basic neurocognition and social cognition appear to influence the social impairments of persons with schizophrenia. This study examined relationships between two very basic automatic processes (i.e., sensorimotor gating and orienting) and social perception in schizophrenic patients. Thirty outpatients with schizophrenia completed psychophysiological measures of sensorimotor gating (prepulse inhibition, PPI), orienting (prepulse facilitation, PPF), and social perception (the Half Profile of Nonverbal Sensitivity, Half PONS). A median split was used to divide patients into poor and good gaters and poor and good orienters. Analyses revealed that patients with good PPI scored significantly higher on the Half PONS than patients with poor PPI. PPI showed a significant correlation (r=-0.54) with Half PONS performance, indicating that schizophrenia patients who were better able to gate out competing stimuli (i.e., less startle) were also better at detecting relevant social cues. Orienting (PPF) and social perception were not related. This study is the first to our knowledge to demonstrate an association between sensorimotor gating and social perception. The findings are consistent with other studies that have demonstrated relationships between basic neurocognition and social cognition. By showing a link between sensorimotor gating and social perception, this study supports social cognition's potential role as a mediator of the relationship between neurocognition and social functioning in schizophrenia. (C) 2004 Elsevier B.V All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. RP Wynn, JK (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,MIRECC 210A,Bldg 210, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH-43292, MH-46433, MH14584] NR 39 TC 29 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 2005 VL 73 IS 2-3 BP 319 EP 325 DI 10.1016/j.schres.2004.07.013 PG 7 WC Psychiatry SC Psychiatry GA 892OY UT WOS:000226661100022 PM 15653277 ER PT J AU Tossani, E Cassano, P Fava, M AF Tossani, E Cassano, P Fava, M TI Depression and renal disease SO SEMINARS IN DIALYSIS LA English DT Review ID SEROTONIN-REUPTAKE INHIBITORS; PERITONEAL-DIALYSIS PATIENTS; NATIONAL-COMORBIDITY-SURVEY; PRIMARY-CARE PATIENTS; MAJOR DEPRESSION; TRICYCLIC ANTIDEPRESSANTS; DOUBLE-BLIND; CLINICAL-EFFICACY; SUSTAINED-RELEASE; SOMATIC SYMPTOMS AB Major depressive disorder (MDD) is a highly prevalent disease, frequently characterized by recurrent or chronic course, and by comorbidity with other medical illnesses. The lifetime prevalence of MDD ranges up to 17% in the general population, and it almost doubles in patients with diabetes (9-27%), stroke (22-50%), or cancer (18-39%). Moreover, MDD worsens the prognosis, quality of life, and treatment compliance of patients with comorbid medical illnesses. Similar to what is observed with other comorbid illnesses, MDD worsens the outcome of kidney disease patients by increasing both morbidity and mortality. Treatment of depressive symptoms in renal failure patients increases medication acceptability and therefore potentially improves the overall patient outcome. The issue of the safety of antidepressant treatment in subjects with renal failure is frequently counterbalanced by the risks associated with depression comorbidity, provided that antidepressants with a low volume of distribution and low protein binding are prescribed, and most important, at low initial doses. Screening for CYP isoenzyme interactions with current medications is also recommended before starting antidepressant treatment. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM mfava@partners.org RI Cassano, Paolo/I-6959-2012; OI Tossani, Eliana/0000-0002-6197-4496 NR 109 TC 34 Z9 34 U1 3 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 2005 VL 18 IS 2 BP 73 EP 81 DI 10.1111/j.1525-139X.2005.18217.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 904EF UT WOS:000227478200002 PM 15771649 ER PT J AU Unruh, ML Weisbord, SD Kimmel, PL AF Unruh, ML Weisbord, SD Kimmel, PL TI Health-related quality of life in nephrology research and clinical practice SO SEMINARS IN DIALYSIS LA English DT Article ID STAGE RENAL-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; PERITONEAL-DIALYSIS PATIENTS; URBAN HEMODIALYSIS-PATIENTS; PSYCHOSOCIAL FACTORS; FUNCTIONAL HEALTH; PATIENT; TRANSPLANTATION; SYMPTOMS; DEPRESSION AB Physical, psychosocial, and lifestyle disturbances, along with physical and emotional symptoms, have been shown to impact the health-related quality of life (HRQOL) of those dependent on renal replacement therapy. The value of HRQOL measurement as a tool to improve clinical care has been recognized by patients, clinical investigators, and health care providers. The potential importance of HRQOL assessment lies in the additional information it provides and the impact it has on the clinical decision-making process between a patient and a physician. There remain a multitude of challenges facing renal providers who wish to incorporate HRQOL measurement to improve patient care. These challenges include the clinician's understanding of the conceptual model of HRQOL, the quality of the scientific process that contributed to the current literature on HRQOL, a willingness of the clinician to incorporate HRQOL information into clinical practice, and the logistic difficulties of collecting and applying HRQOL data in a busy practice setting. Arguably, optimizing HRQOL may be the most substantial impact the health care team will have on the person with kidney failure. In order to implement HRQOL assessment at the point of care, providers may consider using computer adaptive testing and scoring algorithms using item response theory, which will allow adequate reliability for interpretation of change among individuals. Moreover, the effective assessment and interpretation of HRQOL will be aided by continued publication of norms, outcomes of randomized controlled trials, and continued experience of investigators and clinicians. C1 Univ Pittsburgh, Med Ctr, Sch Med, Dept Med,Renal Electrolyte Div, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Unruh, ML (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, Dept Med,Renal Electrolyte Div, 3550 Terrace St,A909 Scaife Hall, Pittsburgh, PA 15261 USA. EM unruh@pitt.edu FU NIDDK NIH HHS [K23 DK66006-01] NR 85 TC 67 Z9 68 U1 1 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 2005 VL 18 IS 2 BP 82 EP 90 DI 10.1111/j.1525-139X.2005.18206.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 904EF UT WOS:000227478200003 PM 15771650 ER PT J AU Venkataraman, R Palevsky, P Kellum, JA AF Venkataraman, R Palevsky, P Kellum, JA TI Adequacy of dialysis in acute renal failure SO SEMINARS IN NEPHROLOGY LA English DT Review ID CONTINUOUS VENOVENOUS HEMOFILTRATION; INTENSIVE-CARE UNIT; TOTAL-BODY WATER; REPLACEMENT THERAPY; MAINTENANCE HEMODIALYSIS; RANDOMIZED-TRIAL; CRITICALLY ILL; INTERMITTENT; SURVIVAL; METAANALYSIS C1 Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, CRISMA Lab, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, Scaife Hall,Room 608,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 51 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 2005 VL 25 IS 2 BP 120 EP 124 DI 10.1016/j.semnephrol.2004.09.019 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 918MF UT WOS:000228545200009 PM 15791564 ER PT J AU Karlamangla, AS Singer, BH Williams, DR Schwartz, JE Matthews, KA Kiefe, CI Seeman, TE AF Karlamangla, AS Singer, BH Williams, DR Schwartz, JE Matthews, KA Kiefe, CI Seeman, TE TI Impact of socioeconomic status on longitudinal accumulation of cardiovascular risk in young adults: the CARDIA Study (USA) SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE socioeconomic status; cardiovascular risk factors; longitudinal risk accumulation; growth trajectories; tracking; USA ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; ANALYZING DEVELOPMENTAL TRAJECTORIES; BLOOD-PRESSURE; SOCIAL-CLASS; RACIAL-DIFFERENCES; HEALTH; MORTALITY; TRACKING; RACE AB Our objectives were to describe the trajectories of biological risk factors of cardiovascular disease in young adults, and to study the association of socioeconomic status (SES) with aggregate risk scores that summarize longitudinal risk accumulation from multiple risk factors. We used data from a prospective, bi-racial. cohort study of 18-30-year-old adults in the USA, initiated in 1985, with 10-year follow-up. SES was measured by parental education level. financial hardship during the study, and the participant's education level by the end of the study. We studied growth patterns of seven biological risk factors for cardiovascular disease using a semi-parametric, class-mixture model to identify clusters, of individuals with distinct growth trajectories. Risk scores that summarize risk from all seven risk factors were created to reflect risk at baseline, longitudinal risk change over 10 years. and total accumulated risk. Multivariable regression was used to study their associations with SES within each race/gender group. We found tracking of all seven risk factors: in each case, the cluster with the highest baseline value maintained its position as the highest-risk cluster over the next 10 years. After adjustment for age, lifestyle, and healthcare access. SES was associated inversely with baseline risk score in women (black and white), with risk change score in all four race/gender groups, and with accumulated risk score in women (black and white) and in white men. Our findings suggest that individuals with high overall cardiovascular risk in midlife can be identified by their relatively higher values of risk factors in younger ages and that socioeconomic differences in cardiovascular risk start accumulating early in life. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48106 USA. SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Karlamangla, AS (reprint author), Univ Calif Los Angeles, Sch Med, Div Geriatr, 10945 Le Conte 2339, Los Angeles, CA 90095 USA. EM akarlamangla@mednet.ucla.edu FU NHLBI NIH HHS [N01-HC-48050, N01-HC-48048, N01-HC-48049, N01-HC-95095, N01-HC-48047]; NIA NIH HHS [AG-17056, 1K12AG01004, AG-17265] NR 68 TC 58 Z9 59 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAR PY 2005 VL 60 IS 5 BP 999 EP 1015 DI 10.1016/j.socscimed.2004.06.056 PG 17 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 889YB UT WOS:000226477700008 PM 15589670 ER PT J AU Morgenstern, LB Woodbury-Harris, K Marler, JR AF Morgenstern, LB Woodbury-Harris, K Marler, JR CA NINDS ICH Workshop Participants TI Priorities for clinical research in intracerebral hemorrhage - Report from a National Institute of Neurological Disorders and Stroke Workshop SO STROKE LA English DT Review DE acute care; brain edema; cerebral amyloid angiopathy; hematology; intracerebral hemorrhage; stroke, acute ID TISSUE-PLASMINOGEN-ACTIVATOR; BLOOD-BRAIN-BARRIER; FOCAL CEREBRAL-ISCHEMIA; ANEURYSMAL SUBARACHNOID HEMORRHAGE; PROSPECTIVE RANDOMIZED TRIAL; ACUTE MYOCARDIAL-INFARCTION; COMBINATION-DRUG THERAPY; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; EDEMA FORMATION AB Background and Purpose-Spontaneous intracerebral hemorrhage (ICH) is one of the most lethal stroke types. In December 2003, a National Institute of Neurological Disorders and Stroke (NINDS) workshop was convened to develop a consensus for ICH research priorities. The focus was clinical research aimed at acute ICH in patients. Methods-Workshop participants were divided into 6 groups: ( 1) current state of ICH research; ( 2) basic science; and ( 3) imaging, ( 4) medical, ( 5) surgical, and ( 6) clinical methodology. Each group formulated research priorities before the workshop. At the workshop, these were discussed and refined. Results-Recent progress in management of hemorrhage growth, intraventricular hemorrhage, and limitations in the benefit of open craniotomy were noted. The workshop identified the importance of developing animal models to reflect human ICH, as well as the phenomena of rebleeding. More human ICH pathology is needed. Real-time, high-field magnets and 3-dimensional imaging, as well as high-resolution tissue probes, are ICH imaging priorities. Trials of acute blood pressure-lowering in ICH and coagulopathy reversal are medical priorities. The exact role of edema in human ICH pathology and its treatment requires intensive study. Trials of minimally invasive surgical techniques including mechanical and chemical surgical adjuncts are critically important. The methodologic challenges include establishing research networks and a multi-specialty approach. Waiver of consent issues and standardizing care in trials are important issues. Encouragement of young investigators from varied backgrounds to enter the ICH research field is critical. Conclusions-Increasing ICH research is crucial. A collaborative approach is likely to yield therapies for this devastating form of brain injury. C1 Univ Michigan, Stroke Program, Ann Arbor, MI 48109 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NINDS, Rockville, MD USA. Washington Univ, St Louis, MO USA. Univ Washington, Seattle, WA 98195 USA. Northwestern Univ, Chicago, IL 60611 USA. Scripps Res Inst, La Jolla, CA USA. Univ Texas, Houston, TX USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Columbia Univ, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins, Baltimore, MD USA. Univ Chicago, Chicago, IL 60637 USA. RP Morgenstern, LB (reprint author), Univ Michigan, Stroke Program, 1500 E Med Ctr Dr,TC1920-0316, Ann Arbor, MI 48109 USA. EM lmorgens@umich.edu NR 228 TC 53 Z9 53 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2005 VL 36 IS 3 BP E23 EP E41 DI 10.1161/01.STR.0000155685.77775.4c PG 19 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 902QN UT WOS:000227371700048 ER PT J AU Rattner, DW AF Rattner, DW TI Invited commentary: Making patient safety automatic SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 5 Parkman St,WAC337, Boston, MA 02114 USA. EM drattner@partners.org NR 3 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2005 VL 137 IS 3 BP 302 EP 303 DI 10.1016/j.surg.2004.12.001 PG 2 WC Surgery SC Surgery GA 905SD UT WOS:000227589100009 PM 15746782 ER PT J AU Greene, AK May, JW Winograd, JM AF Greene, AK May, JW Winograd, JM TI Schwannoma of the median nerve: Iatrogenic injury after axillary lymph node biopsy SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Winograd, JM (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Fruit St,Wang 453, Boston, MA 02114 USA. EM jwinograd@partners.org NR 6 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2005 VL 137 IS 3 BP 378 EP 379 DI 10.1016/j.surg.2004.10.007 PG 2 WC Surgery SC Surgery GA 905SD UT WOS:000227589100022 PM 15746795 ER PT J AU Ellsmere, J Mortele, K Sahani, D Maher, M Cantisani, V Wells, W Brooks, D Rattner, D AF Ellsmere, J Mortele, K Sahani, D Maher, M Cantisani, V Wells, W Brooks, D Rattner, D TI Does multidetector-row CT eliminate the role of diagnostic laparoscopy in assessing the resectability of pancreatic head adenocarcinoma? SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE pancreatic head adenocarcinoma; staging; resectability; accuracy ID PHASE HELICAL CT; COMPUTED-TOMOGRAPHY; CANCER; PANCREATICODUODENECTOMY; UNRESECTABILITY; CHEMORADIATION; MALIGNANCIES; CARCINOMA; NEOPLASMS AB Background: We hypothesized that the high-quality images from multidetector-row computed tomography (MDCT) Would lead to improved sensitivity and specificity for predicting resectable pancreatic head adenocarcinoma, thus diminishing the value of staging laparoscopy. Methods: Forty four Consecutive patients underwent thin-section dual-phase MDCT to stage their tumor, followed by an attempted pancreaticoduodenectomy. Four radiologists who were blinded to the operative outcome reviewed the scans and graded the presence of distant and nodal metastases, as well as the degree of arterial and portal involvement. The radiologic criteria for resectability were no distant metastasis, a patent portal vein, and < 50% arterial involvement. Results: The overall resectability for this cohort was 52% (23/44). The 21 unresectable cases, included five liver metastases, three peritoneal metastases, and 13 locally invasive tumors. The negative margin resection rate was 34% (15/44). There were no portal vein resections. The sensitivity and specificity of MDCT for predicting resectability were 96% (22/23) and 33% (7/21), respectively. In this cohort, the positive and negative predictive values were 61% (22/36) and 87.5% (7/8), respectively. As determined by univariate logistic regression, only the degree of arterial involvement was a significant predictor of resectability (p = 0.02). As determined by multivariate logistic regression using both arterial and portal involvement, arterial involvement was predictive (p = 0.03) but portal vein involvement was not (p = 0.45). Conclusions: Despite the improvements in image quality obtained with rnultidetector-row technology, CT imaging remains a relatively nonspecific test for predicting resectability in patients with adenocarcinoma of the head of the pancreas. Minimally invasive modalities with higher specificity, particularly laparoscopy, continue to have an important role in staging pancreatic head adenocarcinoma. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Ctr Integrat Med & Innovat Technol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Rattner, D (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. OI CANTISANI, VITO/0000-0003-1525-214X NR 16 TC 37 Z9 42 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAR PY 2005 VL 19 IS 3 BP 369 EP 373 DI 10.1007/s00464-004-8712-5 PG 5 WC Surgery SC Surgery GA 924YM UT WOS:000229017300016 PM 15624058 ER PT J AU Maithel, SK Villegas, L Stylopoulos, N Dawson, S Jones, DB AF Maithel, SK Villegas, L Stylopoulos, N Dawson, S Jones, DB TI Simulated laparoscopy using a head-mounted display vs traditional video monitor - An assessment of performance and muscle fatigue SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE computer enhanced laparoscopic training system (CELTS) laparoscopy; ergonomics; visual gaze; electromyography (EMG) ID INSTRUMENT ERGONOMICS WORKSTATION; ENDOSCOPIC SURGERY; OPERATORS; POSTURE; GAZE AB Background: The direction of visual gaze may be an important ergonomic factor that affects operative performance. We designed a study to determine whether a head-mounted display (HMD) worn by the surgeon would improve task performance and/or reduce muscle fatigue during a laparoscopic task when compared to the use of a traditional video monitor display (VMD). Methods: Surgical residents (n = 30) were enrolled in the study. A Junior group, consisting of 15 postgraduate year (PGY) 1 subjects with no previous laparoscopic experience, and a senior group, consisting of 15 PGY 4 and PGY 5 subjects with experience, completed a laparoscopic task that was repeated four times using the Computer Enhanced Laparoscopic Training System (CELTS). Groups alternated between using the HMD with the task placed in a downward frontal position and the VMD with the task at a 30&DEG; lateral angle. The CELTS module assessed task completion time, depth perception, path length of instruments, response orientation, motion smoothness; the system then generated an overall score. Electromyography (EMG) was used to record sternocleidomastoid muscle activity. Display preference was surveyed. Results: The senior residents performed better than the junior residents overall on all parameters (p < 0.05) except for motion smoothness, where there was no difference. In both groups, the HMD significantly improved motion smoothness when compared to the VMD (p < 0.05). All other parameters were equal. There was less muscle fatigue when using the VMD (p < 0.05). We found that 66% of the junior residents but only 20% of the senior residents preferred the HMD. Conclusions: The CELTS module demonstrated evidence of construct validity by differentiating the performances of junior and senior residents. By aligning the surgeon's visual gaze with the instruments, HMD improved smoothness of motion. Experienced residents preferred the traditional monitor display. Although the VMD produced less muscle fatigue, inexperienced residents preferred the HMD, possibly because of improved smoothness of motion. C1 Beth Israel Deaconess Med Ctr, Dept Minimally Invas Surg, Boston, MA 02215 USA. CIMIT, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Ctr Minimally Invas Surg, Boston, MA 02215 USA. RP Jones, DB (reprint author), Beth Israel Deaconess Med Ctr, Dept Minimally Invas Surg, 330 Brookline Ave, Boston, MA 02215 USA. NR 17 TC 20 Z9 20 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAR PY 2005 VL 19 IS 3 BP 406 EP 411 DI 10.1007/s00464-004-8177-6 PG 6 WC Surgery SC Surgery GA 924YM UT WOS:000229017300024 PM 15624063 ER PT J AU Kelly, PA Haidet, P Schneider, V Searle, N Seidel, CL Richards, BE AF Kelly, PA Haidet, P Schneider, V Searle, N Seidel, CL Richards, BE TI A comparison of in-class learner engagement across lecture, problem-based learning, and team learning using the STROBE classroom observation tool SO TEACHING AND LEARNING IN MEDICINE LA English DT Article AB Background: Having recently introduced team learning into the preclinical medical curriculum, evidence of the relative impact of this instructional method on in-class learner engagement was sought. Purpose: To compare patterns of engagement behaviors among learners in class sessions across 3 distinct instructional inethods: lecture, problem-based learning (PBL), and team learning. Methods: Trained observers used the STROBE classroom observation tool to measure learner engagement in 7 lecture, 4 PBL, and 3 team learning classrooms oiler a 12-month period. Proportions of different types of engagement behaviors were compared using chi-square. Results: In PBL and team learning, the amount of learner-to-learner engagement was similar and much greater than in lecture, where most engagement was of the learner-to-instructor and self-engagement types. Also, learner-to-instructor engagement appeared greater in team learning than in PBL. Conclusions: Observed engagement behaviors confirm the potential of team learning to foster engagement similar to PBL, but with greater faculty input. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Kelly, PA (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM pakelly@bcm.edu NR 18 TC 47 Z9 49 U1 1 U2 15 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PD SPR PY 2005 VL 17 IS 2 BP 112 EP 118 DI 10.1207/s15328015tlm1702_4 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 915YH UT WOS:000228347100004 PM 15833720 ER PT J AU Aujesky, D Smith, KJ Cornuz, J Roberts, MS AF Aujesky, D Smith, KJ Cornuz, J Roberts, MS TI Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE cost-effectiveness; treatment; cancer; venous thromboembolism ID DEEP-VEIN THROMBOSIS; LONG-TERM SURVIVAL; PULMONARY-EMBOLISM; BLEEDING COMPLICATIONS; THROMBOLYTIC THERAPY; UNITED-STATES; WARFARIN; PREVENTION; STROKE; MANAGEMENT AB Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was $149,865/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of $15,329. Overall, 46% ($7108) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of $7,609. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin. C1 Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sect Decis Sci & Clin Syst Modeling, Dept Med, Pittsburgh, PA USA. Univ Lausanne, Dept Internal Med, Lausanne, Switzerland. Univ Lausanne, Univ Outpatient Clin, Lausanne, Switzerland. Univ Lausanne, Clin Epidemiol Ctr, Inst Social & Prevent Med, Lausanne, Switzerland. RP Aujesky, D (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 28,Suite 1A129, Pittsburgh, PA 15240 USA. EM aujesky@swissonline.ch NR 38 TC 12 Z9 14 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAR PY 2005 VL 93 IS 3 BP 592 EP 599 DI 10.1160/TH04-11-0767 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 908RT UT WOS:000227808200031 PM 15735815 ER PT J AU Tian, WM Hou, SP Ma, J Zhang, CL Xu, QY Lee, IS Li, HD Spector, M Cui, FZ AF Tian, WM Hou, SP Ma, J Zhang, CL Xu, QY Lee, IS Li, HD Spector, M Cui, FZ TI Hyaluronic acid-poly-D-lysine-based three-dimensional hydrogel for traumatic brain injury SO TISSUE ENGINEERING LA English DT Article ID PERIPHERAL-NERVE REGENERATION; EXTRACELLULAR-MATRIX; RAT; SYSTEM; DELIVERY; IMPLANT; CULTURE; GROWTH AB Brain tissue engineering in the postinjury brain represents a promising option for cellular replacement and rescue, providing a cell scaffold for either transplanted or resident cells. In this article, a hyaluronic acid ( HA)-poly-D-lysine (PDL) copolymer hydrogel with an open porous structure and viscoelastic properties similar to neural tissue has been developed for brain tissue engineering. The chemicophysical properties of the hydrogel with HA: PDL ratios of 10:1, 5:1, and 4:1 were investigated by scanning electron microscopy (SEM) and X-ray photoelectron spectrometry. Neural cells cultured in the hydrogel were studied by phase-contrast microscope and SEM. The incorporation of PDL peptides into the HA-PDL hydrogel allowed for the modulation of neuronal cell adhesion and neural network formation. Macrophages and multinucleated foreign body giant cells found at the site of implantation of the hydrogel in the rat brain within the first weeks postimplantation decreased in numbers after 6 weeks, consistent with the host response to inert implants in numerous tissues. Of importance was the infiltration of the hydrogel by glial fibrillary acidic protein-positive cells-reactive astrocytes-by immunohistochemistry and the contiguity between the hydrogel and the surrounding tissue demonstrated by SEM. These findings indicated the compatibility of this hydrogel with brain tissue. Collectively, the results demonstrate the promise of an HA-PDL hydrogel as a scaffold material for the repair of defects in the brain. C1 Tsing Hua Univ, Dept Mat Sci & Engn, Biomat Lab, Beijing 100084, Peoples R China. Capital Univ Med Sci, Beijing Inst Neurosci, Beijing, Peoples R China. Yonsei Univ, Atom Scale Surface Sci Res Ctr, Seoul, South Korea. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. Yonsei Univ, Inst Phys & Appl Phys, Seoul, South Korea. Yonsei Univ, Ctr Nano Technol, Seoul, South Korea. RP Cui, FZ (reprint author), Tsing Hua Univ, Dept Mat Sci & Engn, Biomat Lab, Beijing 100084, Peoples R China. EM cuifz@mail.tsinghua.edu.cn RI Ma, Jun/K-2084-2012; OI Ma, Jun/0000-0001-5167-1750; Tian, Weiming/0000-0003-4958-4118 NR 33 TC 112 Z9 118 U1 2 U2 48 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD MAR PY 2005 VL 11 IS 3-4 BP 513 EP 525 DI 10.1089/ten.2005.11.513 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 924SA UT WOS:000228999400019 PM 15869430 ER PT J AU Lichterfeld, M Yu, XG Le Gall, S Altfeld, M AF Lichterfeld, M Yu, XG Le Gall, S Altfeld, M TI Immunodominance of HIV-1-specific CD8(+) T-cell responses in acute HIV-1 infection: at the crossroads of viral and host genetics SO TRENDS IN IMMUNOLOGY LA English DT Review ID VIRUS TYPE-1 INFECTION; CLASS-I MOLECULE; LYMPHOCYTE RESPONSES; ACUTE-PHASE; EXPRESSION KINETICS; IMMUNE-RESPONSES; AUTOLOGOUS VIRUS; ESCAPE MUTATION; CTL RESPONSES; EPITOPE AB The development of HIV-1-specific CD8(+) T-cell responses during acute HIV-1 infection is associated with a dramatic decline in HIV-1 replication and the resolution of the acute retroviral syndrome. These HIV-1-specific CD8+ T cells typically target a small number of viral epitopes in a distinct hierarchical order, and high-level viremia in chronic progressive infection leads to broadly diversified HIV-1-specific CD8+ T-cell responses with a less clear immunodominance pattern. It is argued here that the specific hierarchical pattern of immune responses in acute HIV-1 infection is the result of a tightly regulated process that, among other factors, is critically impacted by the kinetics of viral protein expression, the HLA class I background of the infected individual and the autologous sequence of the infecting virus. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. EM maltfeld@partners.org NR 62 TC 36 Z9 37 U1 0 U2 4 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 MAR PY 2005 VL 26 IS 3 BP 166 EP 171 DI 10.1016/j.it.2005.01.003 PG 6 WC Immunology SC Immunology GA 909NE UT WOS:000227865800008 PM 15745859 ER PT J AU Sifri, CD Begun, J Ausubel, FM AF Sifri, CD Begun, J Ausubel, FM TI The worm has turned - microbial virulence modeled in Caenorhabditis elegans SO TRENDS IN MICROBIOLOGY LA English DT Review ID HOST-PATHOGEN INTERACTIONS; INNATE IMMUNE-SYSTEM; PSEUDOMONAS-AERUGINOSA; SALMONELLA-TYPHIMURIUM; CRYPTOCOCCUS-NEOFORMANS; SIGNALING PATHWAY; GENETIC-ANALYSIS; C-ELEGANS; INFECTION; RESISTANCE AB The nematode Caenorhabditis elegans is emerging as a facile and economical model host for the study of evolutionarily conserved mechanisms of microbial pathogenesis and innate immunity. A rapidly growing number of human and animal microbial pathogens have been shown to injure and kill nematodes. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. C. elegans has been used in mutation-based screening systems to identify novel virulence-related microbial genes and immune-related host genes, many of which have been validated in mammalian models of disease. C. elegans-based pathogenesis systems hold the potential to simultaneously explorethe molecular genetic determinants of both pathogen virulence and host defense. C1 Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, MR4, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, MR4, Charlottesville, VA 22908 USA. EM ausubel@molbio.mgh.harvard.edu RI Begun, Jakob/J-6793-2014 OI Begun, Jakob/0000-0001-5256-7672 NR 65 TC 172 Z9 180 U1 5 U2 13 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAR PY 2005 VL 13 IS 3 BP 119 EP 127 DI 10.1016/j.tim.2005.01.003 PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 910LL UT WOS:000227932800008 PM 15737730 ER PT J AU Freedland, SJ Aronson, WJ AF Freedland, SJ Aronson, WJ TI Obesity and prostate cancer SO UROLOGY LA English DT Review ID GROWTH-FACTOR-I; BODY-MASS INDEX; IGF-BINDING PROTEIN-3; DIABETES-MELLITUS; RADICAL PROSTATECTOMY; NORWEGIAN MEN; UNITED-STATES; FOLLOW-UP; PATHOLOGICAL VARIABLES; PHYSICAL-ACTIVITY C1 Johns Hopkins Sch Med, Dept Urol, Brady Urol Inst, Baltimore, MD 21287 USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. RP Freedland, SJ (reprint author), Johns Hopkins Sch Med, Dept Urol, Brady Urol Inst, 600 N Wolfe St, Baltimore, MD 21287 USA. EM sfreedl1@jhmi.edu FU NCI NIH HHS [CA100938, P50 CA92131-01A1] NR 59 TC 29 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAR PY 2005 VL 65 IS 3 BP 433 EP 439 DI 10.1016/j.urology.2004.08.035 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 908PT UT WOS:000227800400004 PM 15780350 ER PT J AU Lin, DD Schultz, D Renshaw, AA Rubin, MA Richie, JP D'Amico, AV AF Lin, DD Schultz, D Renshaw, AA Rubin, MA Richie, JP D'Amico, AV TI Predictors of short postoperative prostate-specific antigen doubling time for patients diagnosed during PSA era SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; BIOCHEMICAL FAILURE; CANCER; PROGRESSION AB Objectives. To determine the preoperative and postoperative predictors of a short prostate-specific antigen (PSA) doubling time (PSADT) after radical prostatectomy for patients diagnosed during the PSA era. Methods. Between 1989 and 2003, 1785 men underwent radical prostatectomy for 2002 American Joint Committee on Cancer (AJCC) Stage T1c or T2 prostate cancer. Of these men, 205 had documented PSA failure. The PSADT was calculated by assuming first-order kinetics and using a minimum of two detectable postoperative PSA measurements after a previous undetectable level. Multivariable logistic regression analyses were performed to determine the significant preoperative and postoperative predictors of a PSADT of less than 6 months. Results. Patients with a greater biopsy Gleason score (P = 0.006), greater preoperative risk group (P = 0.002), greater prostatectomy Gleason score (P = 0.0006), greater 2002 AJCC pathologic stage (P = 0.01), or shorter time to postoperative PSA failure (P = 0.04) were more likely to have a shorter PSADT. Using multivariable analysis, high-risk disease (P = 0.0001) was the only preoperative factor that remained an independent significant predictor of a PSADT of less than 6 months. Of the postoperative factors, a prostatectomy Gleason score of 8 to 10 (P = 0.002), 2002 AJCC pathologic Stage T3b (P = 0.03), and time to PSA failure of less than 2 years (P = 0.05) remained significant independent predictors of a PSADT of less than 6 months. Conclusions. High-risk disease preoperatively and a prostatectomy Gleason score of 8 to 10, seminal vesicle invasion, or a time to PSA failure of less than 2 years postoperatively were significant independent indicators of developing a postoperative PSADT of less than 6 months. For these men, trials studying systemic therapy in addition to radical prostatectomy are needed. (c) 2005 Elsevier Inc. C1 Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Dept Biostat, Millersville, PA 17551 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Lin, DD (reprint author), Brigham & Womens Hosp, Dept Urol, 45 Francis St,ASB-2,3rd Floor, Boston, MA 02115 USA. EM dlin4@partners.org OI Rubin, Mark/0000-0002-8321-9950 NR 11 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAR PY 2005 VL 65 IS 3 BP 528 EP 532 DI 10.1016/j.urology.2004.10.041 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 908PT UT WOS:000227800400024 PM 15780370 ER PT J AU Clarke, P DeBiasi, RL Goody, R Hoyt, CC Richardson-Burns, S Tyler, KL AF Clarke, P DeBiasi, RL Goody, R Hoyt, CC Richardson-Burns, S Tyler, KL TI Mechanisms of reovirus-induced cell death and tissue injury: Role of apoptosis and virus-induced perturbation of host-cell signaling and transcription factor activation SO VIRAL IMMUNOLOGY LA English DT Review ID NF-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; DOUBLE-STRANDED-RNA; ATTACHMENT PROTEIN SIGMA-1; CARDIAC MYOCYTE CULTURES; TOLL-LIKE RECEPTOR-3; GENE-EXPRESSION; SIALIC-ACID; INHIBITION PROTECTS; ANTIVIRAL ACTIVITY AB Reoviruses have provided insight into the roles played by specific viral genes and the proteins they encode in virus-induced cell death and tissue injury. Apoptosis is a major mechanism of cell death induced by reoviruses. Reovirus-induced apoptosis involves both death-receptor and mitochondrial cell death pathways. Reovirus infection is associated with selective activation of mitogen activated protein kinase (MAPK) cascades including JNK/SAPK. Infection also perturbs transcription factor signaling resulting in the activation of c-Jun and initial activation followed by strain-specific inhibition of NF-kappa B. Infection results in changes in the expression of genes encoding proteins involved in cell cycle regulation, apoptosis, and DNA damage and repair processes. Apoptosis is a major mechanism of reovirus-induced injury to key target organs including the CNS and heart. Inhibition of apoptosis through the use of caspase or calpain inhibitors, minocycline, or in caspase 3(-/-) mice all reduce virus-associated tissue injury and enhance survival of infected animals. Reoviruses induce apoptotic cell death (oncolysis) in a wide variety of cancer cells and tumors. The capacity of reoviruses to grow efficiently in transformed cells is enhanced by the presence of an activated Ras signaling pathway likely through mechanisms involving inhibition of antiviral PKR signaling and activation of Ras/RaIGEF/p38 pathways. The potential of reovirus-induced oncolysis in therapy of human cancers is currently being investigated in phase I/II clinical trials. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Program Neurosci, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, 4200 E 9th Ave, Denver, CO 80262 USA. EM Ken.Tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NIAID NIH HHS [5K08AI52261, K08 AI052261]; NINDS NIH HHS [R01 NS051403, R01 NS050138-04, R01 NS051403-03, R01 NS050138] NR 104 TC 27 Z9 29 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD SPR PY 2005 VL 18 IS 1 BP 89 EP 115 DI 10.1089/vim.2005.18.89 PG 27 WC Immunology; Virology SC Immunology; Virology GA 915EW UT WOS:000228281800009 PM 15802955 ER PT J AU Patten, LC Berger, DH AF Patten, LC Berger, DH TI Role of proteases in pancreatic carcinoma SO WORLD JOURNAL OF SURGERY LA English DT Article ID PLASMINOGEN-ACTIVATOR SYSTEM; MATRIX-METALLOPROTEINASE INHIBITORS; TIMP-2 MESSENGER-RNAS; NEUTROPHIL ELASTASE; TUMOR INVASION; CANCER CELLS; MATRILYSIN EXPRESSION; COLORECTAL NEOPLASIA; UROKINASE RECEPTOR; LIVER METASTASIS AB Proteases play an important role in cancer invasion and metastasis. In this review we specifically discuss the role of these proteases in pancreatic carcinoma. Serine proteases and matrix metalloproteinases are the focus of intense research, as they appear to be related to the process of tumor progression. We discuss the diagnostic and prognostic value of these two groups of proteases. Lastly, we report on the current and recent clinical trials focusing on inhibition of these proteases. C1 Baylor Coll Med, Michael E DeBakey, Dept Surg, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Operat Care Line, Houston, TX 77030 USA. RP Berger, DH (reprint author), Baylor Coll Med, Michael E DeBakey, Dept Surg, 6550 Fannin St, Houston, TX 77030 USA. EM dhb@bcm.tmc.edu NR 75 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAR PY 2005 VL 29 IS 3 BP 258 EP 263 DI 10.1007/s00268-04-7816-3 PG 6 WC Surgery SC Surgery GA 910TO UT WOS:000227955300002 PM 15706437 ER PT J AU Emmanouilidou, E Tannous, B Ioannou, PC Christopoulos, TK AF Emmanouilidou, E Tannous, B Ioannou, PC Christopoulos, TK TI Duplex RT-PCR and chemiluminometric hybridization assay for combined screening of the mRNAs of prostate-specific antigen and prostate-specific membrane antigen in peripheral blood SO ANALYTICA CHIMICA ACTA LA English DT Article DE duplex RT-PCR; prostate-specific antigen; prostate-specific membrane antigen; chemiluminescence; hybridization ID POLYMERASE-CHAIN-REACTION; HUMAN GLANDULAR KALLIKREIN; BIOCHEMICAL RECURRENCE; CANCER PATIENTS; CELLS; EXPRESSION AB Combined screening of the mRNAs for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) has been proposed as a more useful test than the separate PSA mRNA or PSMA mRNA assays in the molecular diagnosis and monitoring of prostate cancer. We have developed a simple and highly sensitive method for the simultaneous detection of PSA mRNA and PSMA mRNA using duplex RT-PCR and a chemiluminometric hybridization assay. Total RNA from peripheral blood was reverse-transcribed using oligo(dT)(20) primer followed by duplex PCR in the presence of two pairs of primers specific for PSA and PSMA. Heat-denatured biotinylated PCR products were hybridized with PSA- and PSMA-specific oligonucleotide probes immobilized in microtiter wells. The hybrids were determined by using a streptavidin-alkaline phosphatase conjugate and a chemiluminogenic substrate. Using the duplex PCR, 50 copies of PSA DNA and 5 copies of PSMA DNA can be detected with a signal/background ratio of 9.7 and 22, respectively. Analysis of samples containing total RNA corresponding to 0.04-400 LNCaP cells indicated that the detectability of the proposed method is 1 cancer cell equivalent in 10 ml of peripheral blood. The overall reproducibility of the duplex assay, including reverse transcription, PCR, and hybridization assay, ranged from 3.6 to 15.5%. The method is very simple, rapid, sensitive and suitable for high-throughput screening analysis as opposed to the commonly used nested RT-PCR assays with electrophoretic detection. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Athens, Dept Chem, GR-15771 Athens, Greece. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Patras, Dept Chem, Patras 26500, Greece. Inst Chem Engn & High Temp Chem Proc, Patras 26500, Greece. RP Ioannou, PC (reprint author), Univ Athens, Dept Chem, GR-15771 Athens, Greece. EM ioannou@chem.uoa.gr OI Ioannou, Penelope/0000-0002-2595-1385 NR 23 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD FEB 28 PY 2005 VL 531 IS 2 BP 193 EP 198 DI 10.1016/j.aca.2004.10.024 PG 6 WC Chemistry, Analytical SC Chemistry GA 904OY UT WOS:000227508800005 ER PT J AU Hershey, CL Fisher, DE AF Hershey, CL Fisher, DE TI Genomic analysis of the Microphthalmia locus and identification of the MITF-J/Mitf-J isoform SO GENE LA English DT Article DE transcription factor; tissue-specific; alternative splicing; promoter; melanocyte; osteoclast ID TRANSCRIPTION FACTOR FAMILY; RETINAL-PIGMENT EPITHELIUM; GENE; MUTATIONS; MELANOCYTES; EXPRESSION; DEAFNESS; PROMOTERS; PROTEIN; DEFECT AB The deafness-pigmentary disorder Waardenburg Syndrome Type 2 is caused by mutations in the human Microphthalmia-associated transcription factor (MITF) gene. Multiple related deaffiess-pigmentary disorders result from mutations in genes that regulate MITF expression or its activity. Similarly in mouse, homozygous mutations in the Mitf gene disrupt the development of melanocytes as well as retinal pigment epithelial (R-PE) cells, osteoclasts, mast cells, and NK cells. Because abnormalities in Mitf/MITF function are associated with numerous inherited disorders of mouse and man, a detailed understanding of its gene structure is important for both diagnostic and structure/ function analyses. While at least eight distinct isoforms of MITF/Mitf have been identified to date, each differing in their promoter and initial exon usage, the positions of these exons and their order within the locus have yet to be fully defined. In this study, we provide a detailed description of the MITF/Mitf locus, identify corresponding human and mouse isoforms, and utilize an informatics-based approach to identify a novel ninth MITF/Mitf isoform, MITF-J/Mitf-J, which we show is expressed in multiple cell types. The MITF/Mitf locus is over 200 kb in length, with strong but imperfect exon conservation between human and mouse. MITF/Mitf tissue expression data are presented from multiple datasets, including EST expression patterns and isoform-specific RT-PCR. The majority of isoforms were found to be broadly expressed, with the M- and Mc-isoforms being tissue-restricted to melanocytes and mast cells, respectively. Consequently, a detailed characterization of this complex locus may help to identify additional unknown deaffiess-pigmentary syndrome mutations in human kindred and permit a better understanding of tissue-regulated expression that likely underlies divergent biological functions of this factor across multiple cell types. (c) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Program Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol, 44 Binney St,Dana 630, Boston, MA 02115 USA. EM David_Fisher@dfci.harvard.edu NR 28 TC 55 Z9 60 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD FEB 28 PY 2005 VL 347 IS 1 BP 73 EP 82 DI 10.1016/j.gene.2004.12.002 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 909YP UT WOS:000227896900008 PM 15715979 ER PT J AU Takahashi, S Faraone, SV Lasky-Su, J Tsuang, MT AF Takahashi, S Faraone, SV Lasky-Su, J Tsuang, MT TI Genome-wide scan of homogeneous subtypes of NIMH genetics initiative schizophrenia families SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; highly familial schizophrenia; genome-wide linkage analysis; D8S1819; D22S1169 ID DEPENDENT DIABETES-MELLITUS; ALZHEIMERS-DISEASE LOCUS; SUSCEPTIBILITY GENES; MILLENNIUM CONSORTIUM; LINKAGE ANALYSIS; ALPHA-GENE; PEDIGREES; SEARCH; BREAST; CANCER AB In the light of the potential etiological heterogeneity of schizophrenia, we reanalyzed the NIMH genetics initiative data for schizophrenia. We performed linkage analyses on schizophrenia families divided into more homogeneous subgroups. The African-American and European-American families were divided into groups that were successively more homogeneous. The first group included schizophrenia families that were highly familial, meaning that they contained a minimum specified number of affected individuals. We also excluded patients with environmental influences that may affect disease status. These influences included obstetric complications (OC) and viral infections during the neurodevelopmental stage (VIN). In the African-American sample, a linkage analysis of highly familial schizophrenia families without any environmental influences resulted in a single-point LOD (SLOD) score of 2.90, a multipoint LOD (MLOD) of 2.11, a single-point heterogeneity LOD (SHLOD) score of 3.04, and a multipoint heterogeneity LOD (MHLOD) score of 2.11 at marker D8S1819 (8p23.1) under a dominant parametric model. The highly familial European-American schizophrenia families resulted in an SLOD of 0.91 and an MLOD of 1.85, an SHLOD of 1.64 and an MHLOD of 1.97 at marker D22S1169 (22q13.32) using a recessive parametric model. Although this work should be interpreted cautiously and requires replication, these results suggest that schizophrenia may be linked to chromosomal regions 8p23.1 and 22q12.3-q13.32. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 SUN Upstate Med Univ, Med Genet Res Program, Syracuse, NY 13210 USA. SUN Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. Nihon Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Faraone, SV (reprint author), SUN Upstate Med Univ, Med Genet Res Program, Syracuse, NY 13210 USA. EM svfaraone@yahoo.com OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [5 UO1MH46318, R01MH43518, R01MH44292, 1 R37MH43518, R01MH59624, 1 R01MH41874-01, R01MH60485, R25MH60485, U01 MH46318, UO1MH46276, UO1MH46289] NR 40 TC 20 Z9 22 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB 28 PY 2005 VL 133 IS 2-3 BP 111 EP 122 DI 10.1016/j.psychres.2004.12.003 PG 12 WC Psychiatry SC Psychiatry GA 908UG UT WOS:000227815100001 PM 15740987 ER PT J AU Gurrera, RJ Salisbury, DF O'Donnell, BF Nestor, PG McCarley, RW AF Gurrera, RJ Salisbury, DF O'Donnell, BF Nestor, PG McCarley, RW TI Auditory P3 indexes personality traits and cognitive function in healthy men and women SO PSYCHIATRY RESEARCH LA English DT Article DE event-related potentials; partial least squares analysis; personality; cognitive neuroscience ID EVENT-RELATED POTENTIALS; INDIVIDUAL-DIFFERENCES; TRACKING DIFFICULTY; SCALP TOPOGRAPHY; 5-FACTOR MODEL; NORMAL SAMPLE; DUAL-TASK; DISORDER; SCHIZOPHRENIA; AMPLITUDE AB The relationship of the auditory P3 event-related potential to major personality dimensions and neuropsychological performance was examined in psychiatrically healthy men and women (28 male, 15 female) recruited from the community. An auditory oddball paradigm was used to collect P3 amplitude and latency data. Personality traits were measured with the NEO Five-Factor Inventory. Several Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the Digit Symbol Test, and the Trail Making Test comprised the neuropsychological tests. A multivariate statistical procedure (Partial Least Squares) was used to quantify the relationships between P3 variables and personality and neuropsychological performance variables. P3 amplitude was negatively related to Neuroticism and positively related to Extraversion, Openness, Agreeableness and Conscientiousness. Better neuropsychological performance was associated with greater P3 amplitude and earlier latency. Thus, greater P3 amplitude was associated with less deviant personality scores and better neuropsychological performance in healthy subjects. Earlier P3 latency was also associated with better neuropsychological performance. The physiological significance of these relationships is not yet clear, but these results suggest that neural assemblies indexed by P3 may subserve both elemental cognition and healthy personality function. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 VA Boston Healthcare Syst, Boston, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. Indiana Univ, Dept Psychol, Bloomington, IN USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. RP McCarley, RW (reprint author), VA Boston Healthcare Syst, 940 Belmont St 116A, Boston, MA 02301 USA. EM robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [MH-40779, MH-58704, R01 MH6215001] NR 85 TC 22 Z9 24 U1 5 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB 28 PY 2005 VL 133 IS 2-3 BP 215 EP 228 DI 10.1016/j.psychres.2004.09.009 PG 14 WC Psychiatry SC Psychiatry GA 908UG UT WOS:000227815100011 PM 15740997 ER PT J AU Cardenas, VA Studholme, C Meyerhoff, DJ Song, EM Weiner, MW AF Cardenas, VA Studholme, C Meyerhoff, DJ Song, EM Weiner, MW TI Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE alcoholism; magnetic resonance imaging; image processing; segmentation; deformation morphometry ID MAGNETIC-RESONANCE SPECTROSCOPY; WHITE-MATTER; CORPUS-CALLOSUM; ABSTINENT ALCOHOLICS; SEX-DIFFERENCES; GRAY-MATTER; HIGH-RISK; HIPPOCAMPAL VOLUME; MR-IMAGES; YOUNG MEN AB The goals of this study were to measure if chronic active heavy drinking is associated with brain volume loss in nontreatment seeking men and women, and to assess the effect of positive family history of problem drinking on brain structure in heavy drinkers. Automated image processing was used to analyze high-resolution T1-weighted magnetic resonance images from 49 active heavy drinkers and 49 age- and sex-matched light drinkers, yielding gray matter, white matter and cerebrospinal fluid (CSF) volumes within the frontal, temporal, parietal and occipital lobes. Regional brain volume measures were compared as a function of group, sex and their interaction. Within heavy drinkers, volumes were correlated with measures of alcohol consumption and compared as a function of family history of problem drinking. Deformation morphometry explored localized patterns of atrophy associated with heavy drinking or severity of drinking. We found significant gray matter volume losses, but no white matter losses, in active heavy drinkers compared with light drinkers. Women had greater gray matter and smaller white matter and CSF volumes as a percentage of intracranial vault than men. Within heavy drinkers, smaller gray matter volumes were associated with higher current levels of drinking and older age, while a positive family history of problem drinking was associated with smaller CSF volumes. Community-dwelling heavy drinkers who are not in alcoholism treatment have dose-related gray matter volume losses, and family history of problem drinking ameliorates some structural consequences of heavy drinking. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif San Francisco, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Univ Calif San Francisco, 4150 Clement St, San Francisco, CA 94121 USA. EM valerie@itsa.ucsf.edu FU NIA NIH HHS [P01 AG019724-050002]; NIAAA NIH HHS [P01 AA11493, R01 AA10788]; NIMH NIH HHS [R01 MH065392, R01 MH65392] NR 74 TC 65 Z9 67 U1 2 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD FEB 28 PY 2005 VL 138 IS 2 BP 115 EP 130 DI 10.1016/j.pscychresns.2005.01.002 PG 16 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 913GH UT WOS:000228139100003 PM 15766635 ER PT J AU Brambilla, P Stanley, JA Nicoletti, MA Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Brambilla, P Stanley, JA Nicoletti, MA Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI H-1 Magnetic prefrontal resonance spectroscopy study of dorsolateral cortex in unipolar mood disorder patients SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE neuroimaging; affective disorder; mood disorder; NAA; in vivo proton MRS ID MAJOR DEPRESSIVE DISORDER; ANTERIOR CINGULATE CORTEX; CEREBRAL BLOOD-FLOW; N-ACETYL-ASPARTATE; NEUROPSYCHIATRIC DISORDERS; ELECTROCONVULSIVE-THERAPY; BASAL GANGLIA; BRAIN; SCHIZOPHRENIA; ACETYLASPARTATE AB Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo H-1 magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time H-1 MRS examination localized to an 8-cm(3) single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline-containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the progression of the illness. Future H-1 MRS investigations should longitudinally examine the role of illness chronicity on DLPFC abnormalities and their relationship with the symptoms of unipolar disorder. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. Univ Udine, Sch Med, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. Univ Genoa, Adv Biotechnol Ctr, Genoa, Italy. Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 30915, MH 01736] NR 47 TC 24 Z9 24 U1 3 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD FEB 28 PY 2005 VL 138 IS 2 BP 131 EP 139 DI 10.1016/j.pscychresns.2004.12.001 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 913GH UT WOS:000228139100004 PM 15766636 ER PT J AU Lombard, DB Chua, KF Mostoslavsky, R Franco, S Gostissa, M Alt, FW AF Lombard, DB Chua, KF Mostoslavsky, R Franco, S Gostissa, M Alt, FW TI DNA repair, genome stability, and aging SO CELL LA English DT Review ID STRAND BREAK REPAIR; END-JOINING FACTORS; WERNER-SYNDROME FIBROBLASTS; CEREVISIAE LIFE-SPAN; ATM-DEFICIENT MICE; CAUSES EARLY-ONSET; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; CALORIE RESTRICTION; CELLULAR SENESCENCE AB Aging can be defined as progressive functional decline and increasing mortality over time. Here, we review evidence linking aging to nuclear DNA lesions: DNA damage accumulates with age, and DNA repair defects can cause phenotypes resembling premature aging. We discuss how cellular DNA damage responses may contribute to manifestations of aging. We review Sir2, a factor linking genomic stability, metabolism, and aging. We conclude with a general discussion of the role of mutant mice in aging research and avenues for future investigation. C1 Harvard Univ, Childrens Hosp, Sch Med,Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med,Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu NR 115 TC 462 Z9 487 U1 5 U2 63 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD FEB 25 PY 2005 VL 120 IS 4 BP 497 EP 512 DI 10.1016/j.cell.2005.01.028 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 901GR UT WOS:000227271500007 PM 15734682 ER PT J AU Tanzi, RE Bertram, L AF Tanzi, RE Bertram, L TI Twenty years of the Alzheimer's disease amyloid hypothesis: A genetic perspective SO CELL LA English DT Review ID INSULIN-DEGRADING ENZYME; GAMMA-SECRETASE ACTIVITY; BLOOD-BRAIN-BARRIER; HEREDITARY CEREBRAL-HEMORRHAGE; APOLIPOPROTEIN-E GENOTYPE; PRECURSOR PROTEIN GENE; BLOCK SPANNING IDE; BETA-PROTEIN; A-BETA; IN-VIVO AB From Alois Alzheimer's description of Auguste D.'s brain in 1907 to George Glenner's biochemical dissection of beta-amyloid in 1984, the "amyloid hypothesis" of Alzheimer's disease has continued to gain support over the past two decades, particularly from genetic studies. Here we assess the amyloid hypothesis based on both known and putative Alzheimer's disease genes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mass Gen Inst Neurodegenerat Dis, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mass Gen Inst Neurodegenerat Dis, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 104 TC 939 Z9 982 U1 17 U2 172 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD FEB 25 PY 2005 VL 120 IS 4 BP 545 EP 555 DI 10.1016/j.cell.2005.02.008 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 901GR UT WOS:000227271500011 PM 15734686 ER PT J AU McGettrick, AJ Feener, EP Kahn, CR AF McGettrick, AJ Feener, EP Kahn, CR TI Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID POLYMORPHISM; TYROSINE KINASE-ACTIVITY; ARG(972) POLYMORPHISM; DIABETES-MELLITUS; GENE; VARIANT; RESISTANCE; SENSITIVITY; MUTATION; SECRETION AB The most commonly detected polymorphism in human insulin receptor substrate-1 (IRS-1), a glycine to arginine change at codon 972 (G972R), is associated with an increased risk of Type 2 diabetes and insulin resistance. To determine the molecular mechanism by which this polymorphism may be linked to insulin resistance, we produced recombinant peptides comprising amino acid residues 925-1008 from IRS-1 that contain either a glycine or arginine at codon 972 and the two nearby tyrosine phosphorylation consensus sites ((EYMLM)-M-941 and (DYMTM)-M-989), which are known binding sites for the p85alpha regulatory subunit of phosphatidylinositol 3-kinase. The wild type peptide could be phosphorylated at these sites in vitro by purified insulin receptor. Introduction of the G972R polymorphism into the peptide reduced the amount of tyrosine phosphorylation by >60%. Pull-down experiments indicated that there was an association between the IRS-1-(925-1008) peptide and the insulin receptor that was markedly enhanced by the presence of the G972R polymorphism. The use of additional overlapping fragments localized this interaction to domains between residues 950-986 of IRS-1 and residues 966-1271 of the insulin receptor, containing the tyrosine kinase domain of the receptor. In addition, the IRS-14925-1008) G972R peptide acted as a competitive inhibitor of insulin receptor and insulin-like growth factor-1 receptor autophosphorylation. Taken together, these data indicate that the G972R naturally occurring polymorphism of IRS-1 not only reduces phosphorylation of the substrate but allows IRS-1 to act as an inhibitor of the insulin receptor kinase, producing global insulin resistance. C1 Harvard Univ, Sch Med, Sect Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Proteom Core, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Sect Cellular & Mol Physiol, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, DK33201, DK34834] NR 39 TC 32 Z9 37 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 FEB 25 PY 2005 VL 280 IS 8 BP 6441 EP 6446 DI 10.1074/jbc.M412300200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 902DT UT WOS:000227332700025 PM 15590636 ER PT J AU Kobayashi, S Boggon, TJ Dayaram, T Janne, PA Kocher, O Meyerson, M Johnson, BE Eck, MJ Tenen, DG Halmos, B AF Kobayashi, S Boggon, TJ Dayaram, T Janne, PA Kocher, O Meyerson, M Johnson, BE Eck, MJ Tenen, DG Halmos, B TI EGFR mutation and resistance of non-small-cell lung cancer to gefitinib SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; IMATINIB RESISTANCE; RANDOMIZED-TRIAL; BCR-ABL; INHIBITOR; SENSITIVITY; ERLOTINIB; THERAPY; TUMORS AB Mutations of the epidermal growth factor receptor ( EGFR) gene have been identified in from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR - mutant, gefitinib-responsive, non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 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. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Case Sch Med, Ireland Canc Ctr, Cleveland, OH 44106 USA. RP Tenen, DG (reprint author), Harvard Inst Med, HIM-954,77 Louis Pasteur Ave, Boston, MA 02215 USA. EM dtenen@bidmc.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [1K12CA87723-01, PA20-CA090578-01A1] NR 24 TC 1948 Z9 2037 U1 32 U2 166 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 FEB 24 PY 2005 VL 352 IS 8 BP 786 EP 792 DI 10.1056/NEJMoa044238 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 899MC UT WOS:000227147500008 PM 15728811 ER PT J AU McDonald, KR Bounds, BC Brachtel, EF Zhu, AX Sahani, D Krakauer, EL Harris, NL Billings, JA AF McDonald, KR Bounds, BC Brachtel, EF Zhu, AX Sahani, D Krakauer, EL Harris, NL Billings, JA TI A 58-year-old man with esophageal cancer and nausea, vomiting, and intractable hiccups - Adenocarcinoma of the esophagus with gastric linitis plastica and functional duodenal obstruction. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PALLIATIVE CARE; OCTREOTIDE C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP McDonald, KR (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. NR 19 TC 13 Z9 13 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 24 PY 2005 VL 352 IS 8 BP 817 EP 825 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 899MC UT WOS:000227147500013 PM 15728815 ER PT J AU Poorkaj, P Moses, L Montimurro, JS Nutt, JG Schellenberg, GD Payami, H AF Poorkaj, P Moses, L Montimurro, JS Nutt, JG Schellenberg, GD Payami, H TI parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism SO BMC NEUROLOGY LA English DT Article ID LEVODOPA-RESPONSIVE PARKINSONISM; RECESSIVE JUVENILE PARKINSONISM; SPINOCEREBELLAR ATAXIA TYPE-2; PSEUDO-DOMINANT INHERITANCE; AUTOSOMAL-DOMINANT; LEWY BODIES; DISEASE; ONSET AB Background: parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage. Methods: We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and >= 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons. Results: Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations. Conclusion: Anticipation is not linked to parkin, and may signify a distinct disease entity. C1 New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ Clin Ctr, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY USA. EM pips@u.washington.edu; lmoses2@tulane.edu; jsm05@health.state.ny.us; nuttj@ohsu.edu; zachdad@u.washington.edu; hpayami@wadsworth.org FU NINDS NIH HHS [R01 NS036960, R01 NS36960] NR 21 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD FEB 22 PY 2005 VL 5 AR 4 DI 10.1186/1471-2377-5-4 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 024HR UT WOS:000236186600001 PM 15725358 ER PT J AU Lu, MJ Kinchen, JM Rossman, KL Grimsley, C Hall, M Sondek, J Hengartner, MO Yajnik, V Ravichandran, KS AF Lu, MJ Kinchen, JM Rossman, KL Grimsley, C Hall, M Sondek, J Hengartner, MO Yajnik, V Ravichandran, KS TI A steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs SO CURRENT BIOLOGY LA English DT Article ID CELL-MIGRATION; CRKII/DOCK180/RAC PATHWAY; RAC ACTIVATION; MYOBLAST CITY; PROTEIN; PHAGOCYTOSIS; MEMBRANE; COMPLEX; DOMAIN; MEMBER AB CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases [1-7]. They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems [4, 6, 8-16]. However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3: Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain and contributed to the GEF activity of the Dock180; ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes. C1 Univ Virginia, Dept Microbiol, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA. Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Ravichandran, KS (reprint author), Univ Virginia, Dept Microbiol, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA. EM ravi@virginia.edu RI Hengartner, Michael/A-7058-2008; Hengartner, Michael/E-6235-2011; OI Hengartner, Michael/0000-0002-7584-596X; Sondek, John/0000-0002-1127-8310 FU NIDDK NIH HHS [DK63933]; NIGMS NIH HHS [GM-64709] NR 21 TC 65 Z9 68 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD FEB 22 PY 2005 VL 15 IS 4 BP 371 EP 377 DI 10.1016/j.cub.2005.01.050 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 901FC UT WOS:000227267400029 PM 15723800 ER PT J AU Chen, H Zhang, SM Schwarzschild, MA Hernan, MA Ascherio, A AF Chen, H Zhang, SM Schwarzschild, MA Hernan, MA Ascherio, A TI Physical activity and the risk of Parkinson disease SO NEUROLOGY LA English DT Article ID MALE HEALTH-PROFESSIONALS; NEUROTROPHIC FACTOR; LIMB-USE; WOMEN; MEN; REPRODUCIBILITY; QUESTIONNAIRE; CONSUMPTION; EXERCISE; VALIDITY AB Objective: To investigate whether greater physical activity is associated with a lower risk of Parkinson disease (PD). Methods: The authors prospectively followed 48,574 men and 77,254 women who provided information on physical activity in 1986 or in early adulthood. During the follow-up, a total of 252 ( male) and 135 ( female) incident PD cases were identified. Results: In men, greater baseline physical activity was associated with a lower PD risk; compared with the lowest quintile, the multivariate relative risk (RR) of PD for the highest quintile was 0.7 (95% CI 0.5 to 1.1; p value, test for trend = 0.007), and the inverse association was still present after excluding the first 10 years of follow-up ( RR = 0.5; p value, test for trend = 0.02). Further, strenuous exercise in early adult life was also inversely related to PD risk in men: compared with men who regularly exercised less than or equal to2 months/year, those with greater than or equal to10 months of strenuous exercise had a 60% lower PD risk (RR = 0.4; p value, test for trend = 0.005). In women, physical activity assessed at baseline was not related to PD risk, whereas strenuous exercise in early adulthood tended to be inversely related to PD risk later in life ( highest vs lowest categories, RR = 0.5, 95% CI 0.2 to 1.4; p value, test for trend = 0.06). Conclusion: This study suggests either that higher levels of physical activity may lower the risk of Parkinson disease ( PD) in men or that men predisposed to PD tend to avoid strenuous physical activity in their early adult years. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chen, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM hchen@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 NR 33 TC 138 Z9 148 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 22 PY 2005 VL 64 IS 4 BP 664 EP 669 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 900HU UT WOS:000227206800017 PM 15728289 ER PT J AU Okumura, K Zhao, MJ DePinho, RA Furnari, FB Cavenee, WK AF Okumura, K Zhao, MJ DePinho, RA Furnari, FB Cavenee, WK TI Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 58-KDA MICROSPHERULE PROTEIN; FHA DOMAIN; PHOSPHORYLATION; PHOSPHATASES; MIGRATION; CELLS AB The PTEN (phosphatase and tensin homologue) tumor suppressor protein contains a single catalytic domain with both lipid and protein phosphatase activities. The remaining C-terminal half of the PTEN protein plays a role in its stability and is mutated in many clinical cancer samples. Here, we report that the PTEN C-terminal domain physically interacts with the forkhead-associated domain of the oncogenic MSP58 protein and that this interaction requires PTEN Thr-366. We further show that while MSP58 transforms Pten-/- mouse embryo fibroblasts (MEFs), concurrent introduction of wild-type PTEN causes a dramatic reduction in the number of MSP58-induced transformed foci. This PTEN-mediated inhibition of cellular transformation requires physical interaction as evidenced by the failure of PTEN(T366A) point mutation (residing within the MSP58 interaction domain) to suppress MSP-58-driven transformation. These observations, together with the capacity of catalytically inactive PTEN mutant (G129R) to suppress MSP58 oncogenicity, support the view that the C-terminal region of PTEN directly provides a previously uncharacterized biological function in its ability to regulate cellular transformation. C1 Univ Calif San Diego, Ludwig Inst Canc Res, San Diego Branch, La Jolla, CA 92093 USA. Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. RP Cavenee, WK (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, San Diego Branch, La Jolla, CA 92093 USA. EM wcavenee@ucsd.edu FU NCI NIH HHS [CA95616, P01 CA095616] NR 18 TC 81 Z9 84 U1 1 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 FEB 22 PY 2005 VL 102 IS 8 BP 2703 EP 2706 DI 10.1073/pnas.0409370102 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 900RQ UT WOS:000227232400009 PM 15659546 ER PT J AU Sund, M Hamano, Y Sugimoto, H Sudhakar, A Soubasakos, M Yerramalla, U Benjamin, LE Lawler, J Kieran, M Shah, A Kalluri, R AF Sund, M Hamano, Y Sugimoto, H Sudhakar, A Soubasakos, M Yerramalla, U Benjamin, LE Lawler, J Kieran, M Shah, A Kalluri, R TI Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; endostatin; tumstatin; thrombospondin-1 ID BASEMENT-MEMBRANE; ADHESION MOLECULES; SOLID TUMORS; IV COLLAGEN; THROMBOSPONDIN-1; GROWTH; ENDOSTATIN; TUMSTATIN; DISEASE; CANCER AB Disruption of the systemic angiogenesis balance to favor enhanced angiogenesis is speculated to represent a key step in the growth of tumors. Although a major emphasis has been placed on the increase of angiogenesis stimulators, such as VEGF, on the disruption of the angiogenic balance, the potential role of the physiological levels of endogenous inhibitors of angiogenesis on tumor growth is poorly understood. Here, we use three independent lines of mice deficient in tumstatin, endostatin, or thrombospondin-1 (TSP-1), to address the role that these endogenous angiogenesis inhibitors play in tumor growth. Our experiments demonstrate that normal physiological levels of these inhibitors serve to retard the growth of tumors, and that their absence leads to enhanced angiogenesis and a 2- to 3-fold increase in tumor growth. The tumor-suppressive action of TSP-1, endostatin, and tumstatin correlates with expression of CD36 receptor, alpha5beta1 integrin, and alphavbeta3 integrin on proliferating endothelial cells, respectively. Moreover, tumors grow 2-fold faster in the tumstatin/TSP-1 double-knockout mice, compared with either the tumstatin- or the TSP-1-deficient mice, strongly suggesting that ceiling rate of cancer growth is not completely dependent on the genetic defects of cancer cells but also depends on the host-derived tumor microenvironment. Additionally, tumor growth in transgenic mice overproducing endostatin specifically in the endothelial cells (a 1.6-fold increase in the circulating levels; mimicking Down's syndrome condition) is 3-fold slower than the tumor growth in wild-type mice. Collectively, our data suggest that physiological levels of endogenous inhibitors of angiogenesis can serve as endothelium-specific tumor suppressors. C1 Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Neurooncol, Boston, MA 02115 USA. RP Kalluri, R (reprint author), Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, Dept Med, Boston, MA 02115 USA. EM rkalluri@bidmc.harvard.edu RI Kalluri, Raghu/E-2677-2015; OI Sund, Malin/0000-0002-7516-9543; Kalluri, Raghu/0000-0002-2190-547X; Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [R01 CA109086, R01 CA106263-03, R01 CA106263, R01 CA109086-03]; NIDDK NIH HHS [R01 DK062987, DK62987, R01 DK055001, DK55001] NR 36 TC 120 Z9 134 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 FEB 22 PY 2005 VL 102 IS 8 BP 2934 EP 2939 DI 10.1073/pnas.0500180102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 900RQ UT WOS:000227232400048 PM 15710885 ER PT J AU Sasaki, Y Vanduffel, W Knutsen, T Tyler, C Tootell, R AF Sasaki, Y Vanduffel, W Knutsen, T Tyler, C Tootell, R TI Symmetry activates extrastriate visual cortex in human and nonhuman primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional MRI; monkey; psychophysics ID INFEROTEMPORAL CORTEX; SEXUAL DIMORPHISM; PERCEPTION; AREAS; FMRI; ATTRACTIVENESS; REPRESENTATION; PATTERNS; OBJECTS; REGION AB Humans often create and appreciate visual symmetry in their environment, and the underlying brain mechanisms have been a topic of increasing interest. Here, symmetric versus random dot stimuli produced robust functional MRI (fMRI) activity in higher-order regions of human visual cortex (especially areas V3A, V4, V7, and LO) but little activity elsewhere in brain. This fMRI response was found both with and without attention controls. Moreover, it was highly correlated with the psychophysical perception of symmetry. Similar symmetry responses were found by using line-based and dot stimuli and were found at a wide range of stimulus sizes and geometric configurations. Weaker symmetry responses were found in analogous regions of macaque visual cortex by using fMRI techniques with higher sensitivity. This evidence suggests that visual symmetry is specifically enhanced in the human brain, but that the underlying neural mechanisms may nevertheless be resolvable in nonhuman primates. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Smith Kettlewell Eye Res Inst, San Francisco, CA 94115 USA. RP Sasaki, Y (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. EM yuka@nmr.mgh.harvard.edu FU NEI NIH HHS [R01 EY13025, R01 EY013025]; NIBIB NIH HHS [R01 EB000790, R01 EB00790 A01]; NIMH NIH HHS [R01 MH067529, R01 MH67529] NR 32 TC 92 Z9 94 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 22 PY 2005 VL 102 IS 8 BP 3159 EP 3163 DI 10.1073/pnas.0500319102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 900RQ UT WOS:000227232400086 PM 15710884 ER PT J AU Mandal, M Borowski, C Palomero, T Ferrando, AA Oberdoerffer, P Meng, FY Ruiz-Vela, A Ciofani, M Zuniga-Pflucker, JC Screpand, I Look, AT Korsmeyer, SJ Rajewsky, K von Boehmer, H Aifantis, I AF Mandal, M Borowski, C Palomero, T Ferrando, AA Oberdoerffer, P Meng, FY Ruiz-Vela, A Ciofani, M Zuniga-Pflucker, JC Screpand, I Look, AT Korsmeyer, SJ Rajewsky, K von Boehmer, H Aifantis, I TI The BCL2A1 gene as a pre-T cell receptorinduced regulator of thymocyte survival SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NF-KAPPA-B; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROTEIN-KINASE-C; LYMPHOCYTE DEVELOPMENT; INDUCED APOPTOSIS; ANTIGEN RECEPTOR; DEFICIENT MICE; BCL-2 HOMOLOG; PT-ALPHA; EXPRESSION AB The pre-T cell receptor (TCR) is expressed early during T cell development and imposes a tight selection for differentiating T cell progenitors. Pre-TCR-expressing cells are selected to survive and differentiate further, whereas pre-TCR- cells are "negatively" selected to die. The mechanisms of pre-TCR-mediated survival are poorly understood. Here, we describe the induction of the antiapoptotic gene BCL2A1 (A1) as a potential mechanism regulating inhibition of pre-T cell death. We characterize in detail the signaling pathway involved in A1 induction and show that A1 expression can induce pre-T cell survival by inhibiting activation of caspase-3. Moreover, we show that in vitro "knockdown" of A1 expression can compromise survival even in the presence of a functional pre-TCR. Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to T cell leukemia in both mice and humans. C1 Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Immunol, Toronto, ON M4N 3M5, Canada. Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00185 Rome, Italy. RP Aifantis, I (reprint author), Univ Chicago, Dept Med, Rheumatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM iaifanti@medicine.bsd.uchicago.edu RI Zuniga-Pflucker, Juan/H-1295-2012; Ferrando, Adolfo /Q-7026-2016; OI Ruiz-Vela, Antonio/0000-0002-4410-6208; Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 FU NCI NIH HHS [CA-21765, P30 CA021765] NR 47 TC 81 Z9 81 U1 0 U2 1 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 FEB 21 PY 2005 VL 201 IS 4 BP 603 EP 614 DI 10.1084/jem.20041924 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 901UH UT WOS:000227306900015 PM 15728238 ER PT J AU Liu, RB Rabkin, SD AF Liu, RB Rabkin, SD TI Oncolytic herpes simplex virus vectors for the treatment of human breast cancer SO CHINESE MEDICAL JOURNAL LA English DT Article DE cancer therapy; herpes simplex virus; oncolytic virus; gene therapy; breast cancer ID SQUAMOUS-CELL CARCINOMA; REPLICATION-COMPETENT; VIRAL THERAPY; STATISTICS; NV1020; TRENDS; LINES; G207 AB Background Oncolytic herpes simplex virus (HSV) vectors can be used for cancer therapy as direct cytotoxic agents, inducers of anti-tumor immune responses, and as expressers of anti-cancer genes. In this study, the efficacy of HSV vectors, G47Delta and NV1023 were examined for the treatment of the human breast cancer. Methods Human breast cancer MDA-MB-435 cells were cultured or implanted subcutaneously in BALB/c nude mice. The cells or tumors were inoculated with G47Delta or NV1023, and cell killing or inhibition of tumor growth determined. Both viruses contained the LacZ gene and expression in infected cells was detected with X-gal histochemistry. Results G47Delta and NV1023 were highly cytotoxic to MDA-MB-435 cells in vitro at very low multiplicities of infection. X-gal staining of infected tumor cells in vitro and in vivo illustrated the replication and spread of both viruses. G47Delta and NV1023 inoculation inhibited tumor growth and prolonged mouse survival. Both vectors behaved similarly. Conclusions Oncolytic HSV vectors, G47Delta and NV1023, were extremely effective at killing human breast cancer cells in vitro and in tumor xenografts in vivo. This novel form of cancer therapy warrants further investigation and consideration of clinical application. C1 Sun Yat Sen Univ, Dept Surg, Affiliated Hosp 1, Guangzhou 510080, Peoples R China. Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Surg Microbiol & Mol Genet, Boston, MA 02115 USA. RP Liu, RB (reprint author), Sun Yat Sen Univ, Dept Surg, Affiliated Hosp 1, Guangzhou 510080, Peoples R China. EM renbinliu@yahoo.com RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 20 TC 8 Z9 11 U1 0 U2 1 PU CHINESE MEDICAL ASSOCIATION PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD FEB 20 PY 2005 VL 118 IS 4 BP 307 EP 312 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 904QA UT WOS:000227511600007 PM 15740669 ER PT J AU McGibbon, CA Krebs, DE Parker, SW Scarborough, DM Wayne, PM Wolf, SL AF McGibbon, CA Krebs, DE Parker, SW Scarborough, DM Wayne, PM Wolf, SL TI Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report SO BMC NEUROLOGY LA English DT Article ID OLDER ADULTS; BALANCE; ADAPTATION; DYSFUNCTION; ARTHRITIS; EXERCISES; SUPPORT; POSTURE; FALLS; SPEED AB Background: Vestibular rehabilitation (VR) is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC), have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown. Methods: We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures ( gait speed, step length, stance duration and step width), lower extremity sagittal plane mechanical energy expenditures ( MEE), and trunk sagittal and frontal plane kinematics ( peak and range of linear and angular velocity), were measured. Results: Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship. Conclusion: Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster gait and reduced excessive hip compensation. The VR group's improvements, however, were not the result of lower extremity neuromuscular pattern changes. Lower-extremity MEE increases corresponded to attenuated forward trunk linear and angular movement in the VR group, suggesting better control of upper body motion to minimize loss of balance. These data support a growing body of evidence that Tai Chi may be a valuable complementary treatment for vestibular disorders. C1 Univ New Brunswick, Inst Biomed Engn, Fredericton, NB E3B 5A3, Canada. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. New England Sch Acupuncture, Watertown, MA 02472 USA. Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA 30322 USA. RP McGibbon, CA (reprint author), Univ New Brunswick, Inst Biomed Engn, POB 4400, Fredericton, NB E3B 5A3, Canada. EM cmcgibb@unb.ca; dkrebs@partners.org; swparker@partners.org; dscarborough@partners.org; PWayne@nesa.edu; swolf@emory.edu RI Wolf, Steven/F-6588-2010 OI Wolf, Steven/0000-0002-9446-8995 FU NCCIH NIH HHS [R21 AT00553-01] NR 48 TC 31 Z9 35 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD FEB 18 PY 2005 VL 5 AR 3 DI 10.1186/1471-2377-5-3 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 024HP UT WOS:000236186400001 PM 15717934 ER PT J AU Kelly, KA Allport, JR Tsourkas, A Shinde-Patil, VR Josephson, L Weissleder, R AF Kelly, KA Allport, JR Tsourkas, A Shinde-Patil, VR Josephson, L Weissleder, R TI Detection of vascular adhesion molecule-1 expression using a novel multimodal nanoparticle SO CIRCULATION RESEARCH LA English DT Article DE cardiovascular diseases; cell adhesion molecules; imaging; inflammation; vasculature ID ENDOTHELIAL-CELLS; DRUG-DELIVERY; P-SELECTIN; ATHEROSCLEROSIS; VCAM-1; ICAM-1; ARTERIOSCLEROSIS; ANGIOGENESIS; DISPLAY; LESIONS AB Endothelial vascular adhesion molecule-1 (VCAM-1) is a critical component of the leukocyte-endothelial adhesion cascade, and its strict temporal and spatial regulation make it an ideal target for imaging and therapy. The goal of this study was to develop novel VCAM-1-targeted imaging agents detectable by MRI and fluorescence imaging using phage display-derived peptide sequences and multimodal nanoparticles (NPs). We hypothesized that VCAM-1 mediated cell internalization of phage display - selected peptides could be harnessed as an amplification strategy to chaperone and trap imaging agents inside VCAM-1-expressing cells, thus improving target-to-background ratios. To accomplish our goal, iterative phage display was performed on murine endothelium under physiological flow conditions to identify a family of VCAM-1-mediated cell-internalizing peptides. One specific sequence, containing the VHSPNKK motif that has homology to the alpha-chain of very late antigen (a known ligand for VCAM-1), was shown to bind VCAM-1 and block leukocyte-endothelial interactions. Compared with VCAM-1 monoclonal antibody, the peptide showed 12-fold higher target-to-background ratios. A VHSPNKK-modified magnetofluorescent NP (VNP) showed high affinity for endothelial cells expressing VCAM-1 but surprisingly low affinity for macrophages. In contrast, a control NP without VCAM-1 - targeting sequences showed no affinity for endothelial cells. In vivo, VNP successfully identified VCAM-1 - expressing endothelial cells in a murine tumor necrosis factor-alpha-induced inflammatory model and colocalized with VCAM-1 - expressing cells in atherosclerotic lesions present in cholesterol-fed apolipoprotein E apoE(-/-) mice. These results indicate that: (1) small peptide sequences can significantly alter targeting of NPs, (2) the used amplification strategy of internalization results in high target-to-background ratios, and (3) this technology is useful for in vivo imaging of endothelial markers. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, 149 13th St,Room 5404, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu RI Tsourkas, Andrew/A-1074-2007 OI Tsourkas, Andrew/0000-0001-7758-1753 FU NCI NIH HHS [CA09362, CA86355, CA92782]; NIBIB NIH HHS [EB000662] NR 27 TC 281 Z9 292 U1 6 U2 48 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB 18 PY 2005 VL 96 IS 3 BP 327 EP 336 DI 10.1161/01.RES.0000155722.17881.dd PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 898PG UT WOS:000227088100010 PM 15653572 ER PT J AU Martemyanov, KA Yoo, PJ Skiba, NP Arshavsky, VY AF Martemyanov, KA Yoo, PJ Skiba, NP Arshavsky, VY TI R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE ACCELERATING PROTEIN; BETA-SUBUNIT; MEMBRANE ANCHOR; NERVOUS-SYSTEM; SIGNALING RGS; MICE LACKING; DOMAIN; R9AP; COMPLEX; PHOTORECEPTORS AB The R7 subfamily of the regulators of G protein signaling (RGS) proteins is represented by four members broadly expressed in the mammalian nervous system. Here we report that in the brain all four R7 proteins form tight complexes with a previously unidentified protein, which we call the R7-binding protein or R7BP. We initially identified R7BP as a protein co-precipitating with the R7 protein, RGS9, from extracts obtained from the striatal region of the brain. We further showed that R7BP forms a tight complex with RGS9 in vitro and that this binding occurs via the N-terminal DEP domain of RGS9. R7BP is expressed throughout the entire central nervous system but not in any of the tested non-neuronal tissues. All four R7 RGS proteins co-precipitate with R7BP from brain extracts and recombinant R7 proteins bind recombinant R7BP with high efficiency. The closest homolog of R7BP is R9A.P which was previously found to interact with RGS9 in photoreceptors. Both R7BP and R9AP are related to the syntaxin subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins involved in vesicular trafficking and exocytosis. In photoreceptors R9AP regulates several critical properties of RGS9 including its intracellular targeting, stability and catalytic activity. This suggests that R7BP interactions with R7 proteins in the brain may also bear major functional significance. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM vadim_arshavsky@meei.harvard.edu FU NEI NIH HHS [EY-12859] NR 29 TC 102 Z9 108 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 FEB 18 PY 2005 VL 280 IS 7 BP 5133 EP 5136 DI 10.1074/jbc.C400596200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 900LT UT WOS:000227217100003 PM 15632198 ER PT J AU Jimenez, D Roda-Navarro, P Springer, TA Casasnovas, JM AF Jimenez, D Roda-Navarro, P Springer, TA Casasnovas, JM TI Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DC-SIGN; CELLULAR RECEPTOR; STRUCTURAL BASIS; LIGAND-BINDING; RHINOVIRUS; OLIGOSACCHARIDES; GLYCOSYLATION; DOMAINS; LFA-1; CELLS AB The crystal structures of the glycosylated N-terminal two domains of ICAM-1 and ICAM-2 provided a framework for understanding the role of glycosylation in the structure and function of intercellular adhesion molecules (ICAMs). The most conserved glycans were less flexible in the structures, interacting with protein residues and contributing to receptor folding and expression. The first N-linked glycan in ICAM-2 contacts an exposed tryptophan residue, defining a conserved glycan-W motif critical for the conformation of the integrin binding domain. The absence of this motif in human ICAM-1 exposes regions used in receptor dimerization and rhinovirus recognition. Experiments with soluble molecules having the N-terminal two domains of human ICAMs identified glycans of the high mannose type N-linked to the second domain of the dendritic cell-specific ICAM-grabbing nonintegrin lectin-ligands ICAM-2 and ICAM-3. About 40% of those receptor molecules bear endoglycosidase H sensitive glycans responsible of the lectin binding activity. High mannose glycans were absent in ICAM-1, which did not bind to the lectin, but they appeared in ICAM-1 mutants with additional N-linked glycosylation and lectin binding activity. N-Linked glycosylation regulate both conformation and immune related functions of ICAM receptors. C1 CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain. Univ Autonoma Madrid, Hosp Univ Princesa, Unidad Biol Mol, Madrid 28006, Spain. CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. RP Casasnovas, JM (reprint author), CSIC, Ctr Nacl Biotecnol, Campus Univ Autonoma, E-28049 Madrid, Spain. EM jcasasnovas@cnb.uam.es RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 NR 30 TC 45 Z9 46 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 FEB 18 PY 2005 VL 280 IS 7 BP 5854 EP 5861 DI 10.1074/jbc.M412104200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 900LT UT WOS:000227217100089 PM 15545280 ER PT J AU Yang, FS Lim, GP Begum, AN Ubeda, OJ Simmons, MR Ambegaokar, SS Chen, PP Kayed, R Glabe, CG Frautschy, SA Cole, GM AF Yang, FS Lim, GP Begum, AN Ubeda, OJ Simmons, MR Ambegaokar, SS Chen, PP Kayed, R Glabe, CG Frautschy, SA Cole, GM TI Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NF-KAPPA-B; ALZHEIMERS-DISEASE; CONGO RED; TRANSGENIC MICE; CHEMOPREVENTIVE AGENT; CLINICAL-TRIAL; CACHE COUNTY; MOUSE MODEL; PROTEIN AB Alzheimer's disease (AD) involves amyloid beta (Abeta) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation. Since the molecular structure of curcumin suggested potential Abeta binding, we investigated whether its efficacy in AD models could be explained by effects on Abeta aggregation. Under aggregating conditions in vitro, curcumin inhibited aggregation (IC50 = 0.8 muM) as well as disaggregated fibrillar Abeta40 (IC50 = 1 muM), indicating favorable stoichiometry for inhibition. Curcumin was a better Abeta40 aggregation inhibitor than ibuprofen and naproxen, and prevented Abeta42 oligomer formation and toxicity between 0.1 and 1.0 muM. Under EM, curcumin decreased dose dependently Abeta fibril formation beginning with 0.125 muM. The effects of curcumin did not depend on Abeta sequence but on fibril-related conformation. AD and Tg2576 mice brain sections incubated with curcumin revealed preferential labeling of amyloid plaques. In vivo studies showed that curcumin injected peripherally into aged Tg mice crossed the blood-brain barrier and bound plaques. When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small beta-amyloid species to block aggregation and fibril formation in vitro and in vivo. These data suggest that low dose curcumin effectively disaggregates Abeta as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD. C1 Univ Calif Los Angeles, Dept Med, Greater Los Angeles VA Healthcare Syst CRECC11E, Sepulveda, CA 91343 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. RP Cole, GM (reprint author), Univ Calif Los Angeles, Dept Med, Greater Los Angeles VA Healthcare Syst CRECC11E, 16111 Plummer St, Sepulveda, CA 91343 USA. EM gmcole@ucla.edu FU NCCIH NIH HHS [R01 AT003008]; NIA NIH HHS [R01 AG013741, P50 AG016570, R01 AG010685]; NINDS NIH HHS [NS43946] NR 65 TC 1051 Z9 1105 U1 42 U2 238 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 FEB 18 PY 2005 VL 280 IS 7 BP 5892 EP 5901 DI 10.1074/jbc.M404751200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 900LT UT WOS:000227217100094 PM 15590663 ER PT J AU Chan, DCM Rosowsky, A AF Chan, DCM Rosowsky, A TI Synthesis of the lipophilic antifolate piritrexim via a palladium(0)-catalyzed cross-coupling reaction SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID PHASE-II TRIAL; AVIUM DIHYDROFOLATE-REDUCTASE; SOLUBLE FOLATE ANTAGONIST; ORAL PIRITREXIM; NECK-CANCER; PNEUMOCYSTIS-CARINII; METASTATIC MELANOMA; TOXOPLASMA-GONDII; BW301U; HEAD AB A regiospecific and convergent route the lipophilic antifolate piritrexim (PTX) is described in which a key step is a Pd(0)-catalyzed cross-coupling reaction between 2-amino-3-cyano-4-methyl-5-bromopyridine and 2,5-dimethoxybenzylzinc chloride to form 2-amino-4-methyl-5-(2,5-dimethoxybenzyl)nicotinonitrile. To complete the synthesis, the amino group is replaced by a more reactive bromine atom via nonaqueous diazotization with tert-butyl nitrite, and the resultant bromo nitrile is cyclized with guanidine. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM andre_rosowsky@dfci.harvard.edu FU NIAID NIH HHS [R01-AI-29904] NR 43 TC 8 Z9 8 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD FEB 18 PY 2005 VL 70 IS 4 BP 1364 EP 1368 DI 10.1021/jo040268z PG 5 WC Chemistry, Organic SC Chemistry GA 898KL UT WOS:000227075600030 PM 15704971 ER PT J AU Campbell, EG AF Campbell, EG TI On the take how medicine's complicity with big business can endanger your health SO SCIENCE LA English DT Book Review C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Stanford St, Boston, MA 02114 USA. EM ecampbell@partners.org NR 1 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 18 PY 2005 VL 307 IS 5712 BP 1049 EP 1049 DI 10.1126/science.1108501 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 900ED UT WOS:000227197300027 ER PT J AU Altshuter, D Clark, AG AF Altshuter, D Clark, AG TI Genetics - Harvesting medical information from the human family tree SO SCIENCE LA English DT Editorial Material ID HUMAN GENOME; POLYMORPHISM; RECOMBINATION; METABOLISM; GENES C1 Harvard Univ, Broad Inst, Boston, MA 02114 USA. MIT, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. RP Altshuter, D (reprint author), Harvard Univ, Broad Inst, Boston, MA 02114 USA. EM altshuler@molbio.mgh.harvard.edu; ac347@cornell.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 14 TC 18 Z9 18 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 18 PY 2005 VL 307 IS 5712 BP 1052 EP 1053 DI 10.1126/science.1109682 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 900ED UT WOS:000227197300029 PM 15718454 ER PT J AU Opferman, JT Iwasaki, H Ong, CC Suh, H Mizuno, S Akashi, K Korsmeyer, SJ AF Opferman, JT Iwasaki, H Ong, CC Suh, H Mizuno, S Akashi, K Korsmeyer, SJ TI Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells SO SCIENCE LA English DT Article ID PROGENITORS; LINEAGES; DEATH; MICE; BAX; BCL-2 AB Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid Leukemia-1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow. This resulted in the Loss of early bone marrow progenitor populations, including HSCs. Moreover, growth factors including stem cell factor increased transcription of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS Pathol & Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS Pathol & Med, 44 Binney St, Boston, MA 02115 USA. EM Koichi_Akashi@dfci.harvard.edu; Stanley_Korsmeyer@dfci.harvard.edu FU NCI NIH HHS [CA072009, R37CA50239]; NIDDK NIH HHS [DK061320] NR 20 TC 317 Z9 333 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 18 PY 2005 VL 307 IS 5712 BP 1101 EP 1104 DI 10.1126/science.1106114 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 900ED UT WOS:000227197300046 PM 15718471 ER PT J AU Sage, C Huang, MQ Karimi, K Gutierrez, G Vollrath, MA Zhang, DS Garcia-Anoveros, J Hinds, PW Corwin, JT Corey, DP Chen, ZY AF Sage, C Huang, MQ Karimi, K Gutierrez, G Vollrath, MA Zhang, DS Garcia-Anoveros, J Hinds, PW Corwin, JT Corey, DP Chen, ZY TI Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein SO SCIENCE LA English DT Article ID INNER-EAR; FATE DETERMINATION; ACOUSTIC TRAUMA; RB; MOUSE; GENE; MUTATION; REGENERATION; SURVIVAL; NEUROGENESIS AB In mammals, hair cell loss causes irreversible hearing and balance impairment because hair cells are terminally differentiated and do not regenerate spontaneously. By profiling gene expression in developing mouse vestibular organs, we identified the retinoblastorna protein (pRb) as a candidate regulator of cell cycle exit in hair cells. Differentiated and functional mouse hair cells with a targeted deletion of Rb1 undergo mitosis, divide, and cycle, yet continue to become highly differentiated and functional. Moreover, acute loss of Rb1 in postnatal hair cells caused cell cycle reentry. Manipulation of the pRb pathway may ultimately lead to mammalian hair cell regeneration. C1 Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. Tufts New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Northwestern Univ, Inst Neurosci, Dept Anesthesiol, Chicago, IL 60611 USA. Northwestern Univ, Inst Neurosci, Dept Physiol, Chicago, IL 60611 USA. Northwestern Univ, Inst Neurosci, Dept Neurol, Chicago, IL 60611 USA. RP Chen, ZY (reprint author), Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair, Neurol Serv, Boston, MA 02114 USA. EM zhengyi@helix.mgh.harvard.edu OI Corey, David/0000-0003-4497-6016; Gutierrez, Gabriel/0000-0001-8487-0414 FU NIDCD NIH HHS [DC-00200, DC-04546, DC-AG20208] NR 30 TC 157 Z9 175 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 18 PY 2005 VL 307 IS 5712 BP 1114 EP 1118 DI 10.1126/science.1106642 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 900ED UT WOS:000227197300050 PM 15653467 ER PT J AU Ojikutu, BO Stone, VE AF Ojikutu, BO Stone, VE TI Women, inequality, and the burden of HIV SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. RP Ojikutu, BO (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 4 TC 23 Z9 24 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 FEB 17 PY 2005 VL 352 IS 7 BP 649 EP 652 DI 10.1056/NEJMp048318 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 897UO UT WOS:000227031100002 PM 15716557 ER PT J AU Biddinger, PD Isselbacher, EM Fan, D Shepard, JO Egan, D Fan, D Harris, NL Parks, L AF Biddinger, PD Isselbacher, EM Fan, D Shepard, JO Egan, D Fan, D Harris, NL Parks, L TI A 53-year-old man with depression and sudden shortness of breath - Invasive endocarditis, possibly due to bartonella SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PSYCHIATRIC-PATIENTS; MEDICAL CLEARANCE; INFECTIVE ENDOCARDITIS; PULMONARY-EDEMA; PERIVALVULAR ABSCESS; MITRAL REGURGITATION; EMERGENCY ROOM C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Biddinger, PD (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 19 TC 5 Z9 5 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 FEB 17 PY 2005 VL 352 IS 7 BP 709 EP 716 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 897UO UT WOS:000227031100012 PM 15716566 ER PT J AU Jaffer, FA Weissleder, R AF Jaffer, FA Weissleder, R TI Molecular imaging in the clinical arena SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; SERVICES-TASK-FORCE; IN-VIVO; NONINVASIVE DETECTION; ATHEROSCLEROTIC PLAQUES; COMPUTED-TOMOGRAPHY; PROSTATE-CANCER; ENZYME-ACTIVITY; DRUG DISCOVERY AB Molecular imaging is an emerging field that aims to integrate patient-specific and disease-specific molecular information with traditional anatomical imaging readouts. The information provided by this field may ultimately allow for noninvasive or minimally invasive molecular diagnostic capabilities, better clinical risk stratification, more optimal selection of disease therapy, and improved assessment of treatment efficacy. In this update, we first provide an overview of clinically relevant molecular imaging technologies and imaging agents. Next, their applications to disease detection, drug discovery, and biomedical research are discussed. To specifically demonstrate the potential of molecular imaging, we highlight recent advances in clinical and preclinical molecular imaging of cancer and atherosclerosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA USA. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 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 NCI NIH HHS [P50-CA86355] NR 55 TC 233 Z9 246 U1 3 U2 27 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 16 PY 2005 VL 293 IS 7 BP 855 EP 862 DI 10.1001/jama.293.7.855 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 897DQ UT WOS:000226984600028 PM 15713776 ER PT J AU Michels, KB Willett, WC Fuchs, CS Giovannucci, E AF Michels, KB Willett, WC Fuchs, CS Giovannucci, E TI Coffee, tea, and caffeine consumption and incidence of colon and rectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; TOTAL-ENERGY-INTAKE; COLORECTAL-CANCER; PROSPECTIVE COHORT; RISK; REPRODUCIBILITY; VALIDITY; HEALTH; CARCINOGENESIS; POPULATION AB Background. Frequent coffee consumption has been associated with a reduced risk of colorectal cancer in a number of case-control studies. Cohort studies have not revealed such an association but were limited in size. We explored the association between consumption of coffee and tea and the incidence of colorectal cancer in two large prospective cohorts of women and men. Methods: We used data from the Nurses' Health Study (women) and the Health Professionals' Followup Study (men). Consumption of coffee and tea and total caffeine intake were assessed and updated in 1980, 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon or rectum was ascertained through 1998. Hazard ratios were calculated using Cox proportional hazards models that adjusted for potential confounders. All tests of statistical significance were two-sided. Results: During almost 2 million person-years of follow-up, 1438 cases of colorectal cancer were observed. Consumption of caffeinated coffee or tea with caffeine or caffeine intake was not associated with the incidence of colon or rectal cancer in either cohort. For both cohorts combined, the covariate-adjusted hazard ratio for colorectal cancer associated with consumption of each additional cup of caffeinated coffee was 0.99 (95% confidence interval [CI] = 0.96 to 1.03). However, participants who regularly consumed two or more cups of decaffeinated coffee per day had a 52% (95% CI = 19% to 71%) lower incidence of rectal cancer than those who never consumed decaffeinated coffee (crude incidence rate of 12 cases of rectal cancer per 100000 person-years of follow-up among participants consuming two or more cups of decaffeinated coffee per day and crude incidence rate of 19 cases of rectal cancer per 100000 person-years of follow-up among participants who never consumed decaffeinated coffee). Conclusions: Consumption of caffeinated coffee, tea with caffeine, or caffeine was not associated with incidence of colon of rectal cancer, whereas regular consumption of decaffeinated coffee was associated with a reduced incidence of rectal cancer. C1 Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michels, KB (reprint author), Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM kmichels@rics.bwh.harvard.edu FU NCI NIH HHS [P01 CA055075, CA87969, P01 CA087969, CA55075]; NIDDK NIH HHS [R01 DK054900-02, R01 DK054900, DK54900] NR 37 TC 79 Z9 79 U1 2 U2 17 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 FEB 16 PY 2005 VL 97 IS 4 BP 282 EP 292 DI 10.1093/jnci/dji039 PG 11 WC Oncology SC Oncology GA 898WW UT WOS:000227107900011 PM 15713963 ER PT J AU Korzenik, JR Dieckgraefe, BK AF Korzenik, JR Dieckgraefe, BK TI An open-labelled study of granulocyte colony-stimulating factor in the treatment of active Crohn's disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CHRONIC GRANULOMATOUS-DISEASE; NEUTROPHIL FUNCTION; ULCERATIVE-COLITIS; CYCLIC NEUTROPENIA; RESPIRATORY BURST; HUMAN VOLUNTEERS; IB; ILEOCOLITIS; TYPE-1B AB Background: Immunodeficiency syndromes associated with a Crohn's-like illness suggest innate immune defects may lead to Crohn's disease. Anecdotal cases using haemopoietic colony-stimulating factors report improvement in intestinal disease associated with these syndromes. Aim: To test the safety and efficacy of recombinant human granulocyte colony-stimulating factor in active Crohn's disease. Methods: In an open-labelled 12-week trial, patients with a Crohn's Disease Activity Index between 220 and 450 were treated with recombinant human granulocyte colony-stimulating factor (filgrastim, Neupogen). Concomitant immunosuppressants were prohibited except prednisone less than or equal to20 mg/day. Patient's received recombinant human granulocyte colony-stimulating factor 300 mcg daily subcutaneously adjusted to achieve an absolute neutrophil count between 25 and 35 x 10(9)/L. Results: Twenty patients were enrolled with a mean initial Crohn's Disease Activity Index of 307 (range: 234-428). Fifteen patients (75%) completed 8 weeks; 13 patients (65%) completed 12 weeks with the mean Crohn's Disease Activity Index for patients continuing through those times of 196 (range: 36-343) and 162 (range: 20-308), respectively. At week 12, 11 patients (55%) demonstrated a decrease of at least 70 points; five (25%) achieved a sustained remission. The mean decrease was statistically significant at each assessment time-point. Three of four patients with fistulae had a positive response. Adverse effects included bone pain, mostly mild resolving with continued treatment. One patient was hospitalized with a viral-like syndrome but it is uncertain if this was treatment related. Conclusion: Recombinant human granulocyte colony-stimulating factor is safe and potentially effective therapy for active Crohn's disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Internal Med, Gastrointestinal Unit,Inflammatory Bowel Dis Ctr, Boston, MA 02114 USA. Washington Univ, Sch Med, Dept Internal Med, Div Gastroenterol, St Louis, MO 63110 USA. RP Korzenik, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Internal Med, Gastrointestinal Unit,Inflammatory Bowel Dis Ctr, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM jkorzenik@partners.org NR 45 TC 55 Z9 56 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD FEB 15 PY 2005 VL 21 IS 4 BP 391 EP 400 DI 10.1111/j.1365-2036.2005.02287.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 897OY UT WOS:000227015700009 PM 15709989 ER PT J AU Otsuji, Y Kuwahara, E Yuge, K Yotsumoto, G Ueno, T Nakashiki, K Hamasaki, S Biro, S Minagoe, S Levine, RA Sakata, R Tei, C AF Otsuji, Y Kuwahara, E Yuge, K Yotsumoto, G Ueno, T Nakashiki, K Hamasaki, S Biro, S Minagoe, S Levine, RA Sakata, R Tei, C TI Relation of aneurysmectomy in patients with advanced left ventricular remodeling to postoperative left ventricular filling pressure, redilatation with ischemic mitral regurgitation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PAPILLARY-MUSCLE DYSFUNCTION; DOPPLER-ECHOCARDIOGRAPHY; MYOCARDIAL-INFARCTION; DETERMINANTS; MECHANISM; DILATION; GEOMETRY AB Left ventricular (LV) volume, mitral E deceleration time, and mitral regurgitation (MR) fraction were measured by echocardiography in 14 patients with surgical LV aneurysmectomy. Late MR developed 3 to 6 months after surgery in 5 of the 14 patients (36%). Compared with patients without late MR, those with late MR had a significantly greater preoperative LV end-diastolic volume index (LVEDVI) (134 +/- 21 vs 93 +/- 19 ml/m(2), p <0.01), surgical reduction in LVEDVI (-51 +/- 14 vs -20 +/- 16 ml/m(2), p <0.01), early postoperative LV diastolic dysfunction with shortened mitral E deceleration time (106 +/- 23 vs 141 +/- 24 ms, p <0.01), and a late postoperative reincrease in LVEDVI (+28 +/- 4 vs +3 +/- 8 ml/m(2), p <0.01), suggesting that surgical LV aneurysmectomy in patients with advanced preoperative LV remodeling may result in postoperative LV diastolic dysfunction, promoting later LV redilation with ischemic MR. (C) 2005 by Excerpta Medica Inc. C1 Kagoshima Univ, Dept Cardiovasc Resp & Metab Med, Grad Sch Med, Kagoshima 8908520, Japan. Kagoshima Univ, Dept Cardiovasc Surg, Grad Sch Med, Kagoshima 8908520, Japan. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Otsuji, Y (reprint author), Kagoshima Univ, Dept Cardiovasc Resp & Metab Med, Grad Sch Med, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM yutaka@m.kufm.kagoshima-u.ac.jp NR 20 TC 5 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 15 PY 2005 VL 95 IS 4 BP 517 EP 521 DI 10.1016/j.amjcard.2004.10.024 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 897EB UT WOS:000226985700020 PM 15695144 ER PT J AU Majahalme, SK Baruch, L Aknay, N Goedel-Meinen, L Hofman, M Hester, A Prescott, MF Feliciano, N AF Majahalme, SK Baruch, L Aknay, N Goedel-Meinen, L Hofman, M Hester, A Prescott, MF Feliciano, N CA Val-HeFT Study Investigators TI Comparison of treatment benefit and outcome in women versus men with chronic heart failure (from the Valsartan Heart Failure Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ANGIOTENSIN-RECEPTOR BLOCKER; LEFT-VENTRICULAR HYPERTROPHY; VAL-HEFT; MORTALITY; SURVIVAL AB The comparison of treatment effect and co-morbidity between the genders in the Valsartan Heart Failure Trial showed equal benefit of treatment in men and women. Co-morbidities, such as diabetes and coronary artery disease, increased nonfatal cardiac morbidity more in women than in men. (C) 2005 by Excerpta Medica Inc. C1 Appleton Heart Inst, Appleton, WI 54911 USA. Tampere Univ, FIN-33101 Tampere, Finland. Bronx Vet Affairs Med Ctr, New York, NY USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Tech Univ Munich, Deutsch Herzzentrum, D-8000 Munich, Germany. RP Majahalme, SK (reprint author), Appleton Heart Inst, 1818 N Meade St, Appleton, WI 54911 USA. EM silja.majahalme@thedacare.org NR 14 TC 7 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 15 PY 2005 VL 95 IS 4 BP 529 EP 532 DI 10.1016/j.amjcard.2004.10.026 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 897EB UT WOS:000226985700023 PM 15695147 ER PT J AU Hinek, A Teitell, MA Schoyer, L Allen, W Gripp, KW Hamilton, R Weksberg, R Kluppel, M Lin, AE AF Hinek, A Teitell, MA Schoyer, L Allen, W Gripp, KW Hamilton, R Weksberg, R Kluppel, M Lin, AE TI Myocardial storage of chondroitin sulfate-containing moieties in costello syndrome patients with severe hypertrophic cardiomyopathy SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE chondroitin sulfate; Costello syndrome; elastin; elastin binding protein; hypertrophic cardiomyopathy; MCA/MR syndrome ID ELASTIN-BINDING-PROTEIN; SMOOTH-MUSCLE-CELLS; FACIO-CUTANEOUS SYNDROME; EXTRACELLULAR-MATRIX; BETA-GALACTOSIDASE; IMPAIRED ELASTOGENESIS; CARDIAC INVOLVEMENT; LAMININ RECEPTOR; SPLICED VARIANT; HURLER-DISEASE AB Costello syndrome is a distinctive multiple congenital anomaly syndrome, characterized by loose soft skin with deep palmar and plantar creases, loose joints, distinctive coarse facial features, skeletal abnormalities, cardiac abnormalities (cardiovascular malformation (CVM), hypertrophic cardiomyopathy, tachycardia), predisposition to malignancy, developmental delays, and mental retardation. Previous studies with cultured fibroblasts from individuals with Costello syndrome demonstrate excessive accumulation of chondroitin sulfate-bearing proteoglycans, associated with both impaired formation of elastic fibers and an unusually high rate of cellular proliferation. Despite multiple clinical reports of cardiac abnormalities, there has been only one previously published report describing post-mortem findings in hearts from Costello syndrome patients. Here we provide a detailed description of the post-mortem findings of the hearts of three children with Costello syndrome. Routine histological examination and results of targeted histochemical and immumohistochemical studies revealed that in addition to cardiomyocyte hypertrophy, these hearts also demonstrated massive pericellular and intracellular accumulation of chondroitin sulfate-bearing proteoglycans and a marked reduction of elastic fibers. Normal stroma. was replaced by multifocal collagenous fibrosis. Most peculiar was the finding that the bulk of the chondroitin sulfate accumulated in these Costello syndrome hearts is a chondroitin-6-sulfate. In contrast, deposition of chondroitin-4 sulfate was below the level detected in normal hearts. We propose that an imbalance in sulfation of chondiroitin sulfate molecules and subsequent accumulation of chondroitin-6-sulfate in cardiomyocytes contribute to the development of the hypertrophic cardiomyopathy of Costello syndrome. (C) 2005 Wiley-Liss, Inc. C1 Hosp Sick Children, Div Cardiovasc Res, Toronto, ON M5G 1X8, Canada. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA USA. Cty Los Angeles Childrens Med Serv, Los Angeles, CA USA. Fullerton Genet Ctr, Asheville, NC USA. AI duPont Hosp Children, Div Med Genet, Wilmington, DE USA. Hosp Sick Children, Div Cardiol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. MassGen Hosp Children, Genet & Teratol Serv, Boston, MA USA. RP Hinek, A (reprint author), Hosp Sick Children, Div Cardiovasc Res, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM alek.hinek@sickkids.on.ca FU NCI NIH HHS [CA90571, CA107300] NR 67 TC 23 Z9 24 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD FEB 15 PY 2005 VL 133A IS 1 BP 1 EP 12 DI 10.1002/ajmg.a.30495 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 891ZJ UT WOS:000226619200001 PM 15637729 ER PT J AU Wu, DW Reginato, AJ Torriani, M Robinson, DR Reginato, AM AF Wu, DW Reginato, AJ Torriani, M Robinson, DR Reginato, AM TI The crowned dens syndrome as a cause of neck pain: Report of two new cases and review of the literature SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Review ID DIHYDRATE DEPOSITION DISEASE; PYROPHOSPHATE CRYSTAL DEPOSITION; FORAMEN MAGNUM SYNDROME; CALCIUM PYROPHOSPHATE; CERVICAL-SPINE; LIGAMENTUM-FLAVUM; CRANIOCERVICAL JUNCTION; COMPUTED-TOMOGRAPHY; TRANSVERSE LIGAMENT; ODONTOID PROCESS C1 Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Cherry Hill, NJ USA. RP Reginato, AM (reprint author), Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM areginato@partners.org NR 41 TC 25 Z9 26 U1 0 U2 1 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 FEB 15 PY 2005 VL 53 IS 1 BP 133 EP 137 DI 10.1002/art.20915 PG 5 WC Rheumatology SC Rheumatology GA 895IL UT WOS:000226854300024 PM 15696551 ER PT J AU Penheiter, AR Filoteo, AG Penniston, JT Caride, AJ AF Penheiter, AR Filoteo, AG Penniston, JT Caride, AJ TI Kinetic analysis of the calmodulin-binding region of the plasma membrane calcium pump isoform 4b SO BIOCHEMISTRY LA English DT Article ID LIGHT-CHAIN KINASE; CA2+ PUMP; CA-2+ PUMP; ACTIVATION; PEPTIDES; COMPLEX; DOMAIN; INHIBITION; MECHANISM; AFFINITY AB The sequence L(1086)RRGQILWFRGLNRIQTQIKVVKAFHSS(1113) (peptide C28) is responsible for calmodulin binding to PMCA4b. In this work, peptides following the above sequence were progressively shortened either at the N-terminus (C28NDelta3, C28NDelta5, or C28NDelta6) or at the C-terminus (C20, C22, C23, and C25). Competitive inhibition of PMCA activity was used to measure apparent dissociation constants of the complexes between calmodulin and C28 or progressively shortened peptides. Additionally, equilibrium titrations were used to measure the apparent dissociation constants of the various peptides with TA-calmodulin by changes in TA-calmodulin fluorescence and Trp fluorescence of the peptides. At the N-terminus, deletion of five residues did not change calmodulin affinity, but deletion of six residues resulted in a 5-fold decrease in affinity. There were no major differences in the time course of TA-CaM binding, but C28NDelta6 exhibited a different time course of Trp fluorescence change. At the C-terminus, deletion of five residues (C23) or more resulted in a net increase in fluorescence of TA-CaM upon binding, while longer peptides (C25 and C28) produced both a transient increase and a net decrease in the fluorescence of TA-CaM. Global regression analysis revealed that binding of TA-CaM to the C23 peptide could be fit by a two-step model, while longer peptides required three-step models for adequate fitting. TA-calmodulin dissociated rapidly from C23, C22, and C20, resulting in a marked increase in apparent K-d. Thus, the sequence I(1091)LWFRGLNRIQTQIKVVKAF(1110) (C25NDelta5) is required to reproduce the calmodulin-binding properties of C28. When F-1110 was replaced by A, the TA-calmodulin association and dissociation kinetics resembled C23 kinetics, but changing V-1107 to A produced a smaller effect, suggesting that F-1110, rather than V-1107, is the main anchor for the N-terminal lobe of calmodulin in PMCA4b. C1 Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USA. Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, Boston, MA 02114 USA. RP Mayo Clin, Dept Biochem & Mol Biol, 200 1st St SW, Rochester, MN 55901 USA. EM caride@mayo.edu FU NIGMS NIH HHS [GM28835] NR 25 TC 19 Z9 19 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 15 PY 2005 VL 44 IS 6 BP 2009 EP 2020 DI 10.1021/bi0488552 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 896YB UT WOS:000226969400026 PM 15697226 ER PT J AU Tamagnan, G Alagille, D Fu, X Kula, NS Baldessarini, RJ Innis, RB Baldwin, RM AF Tamagnan, G Alagille, D Fu, X Kula, NS Baldessarini, RJ Innis, RB Baldwin, RM TI Synthesis and monoamine transporter affinity of new 2 beta-carbomethoxy-3 beta-[4-(substituted thiophenyl)]phenyltropanes: discovery of a selective SERT antagonist with picomolar potency SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE serotonin transporter; tropane; affinity ID DOPAMINE HYPOTHESIS; PLACE PREFERENCE; COCAINE REWARD; SEROTONIN; ANALOGS; MECHANISMS AB Preparation of cocaine analogues has been aimed largely at development of stable compounds with high affinity and selectivity for the dopamine transporter (DAT). We now report the synthesis and monoamine transporter affinity of 10 new 2beta-carbomethoxy-3p-[4-(substituted thiophenyl)]phenyltropanes. Among these, compound 4b exhibited very high affinity for the serotonin transporter (SERT: K-i = 17 pM) and good selectivity over dopamine (DAT: 710-fold) and norepinephrine transporters (NET: 11,100-fold). (C) 2004 Elsevier Ltd. All rights reserved. C1 Yale Univ, Dept Psychiat, West Haven, CT 06516 USA. VA Connecticut, West Haven, CT 06516 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Program Neurosci, Belmont, MA 02478 USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Inst Neurodegenerat Disorders, New Haven, CT 06510 USA. RP Tamagnan, G (reprint author), Yale Univ, Dept Psychiat, 950 Campbell Ave,116A2, West Haven, CT 06516 USA. EM gtamagnan@indd.org FU NIMH NIH HHS [MH67066-01] NR 12 TC 14 Z9 14 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 15 PY 2005 VL 15 IS 4 BP 1131 EP 1133 DI 10.1016/j.bmcl.2004.12.014 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 899HL UT WOS:000227135400052 PM 15686927 ER PT J AU Podar, K Anderson, KC AF Podar, K Anderson, KC TI The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications SO BLOOD LA English DT Review ID ENDOTHELIAL-GROWTH-FACTOR; MULTIPLE-MYELOMA CELLS; VASCULAR-PERMEABILITY FACTOR; BONE-MARROW ANGIOGENESIS; PROTEASOME INHIBITOR PS-341; PROTEIN-KINASE-C; OVERCOMES DRUG-RESISTANCE; RECEPTOR TYROSINE KINASES; DISTINCT SIGNALING PATHWAYS; HEMATOPOIETIC STEM-CELLS AB Besides its role as an essential regulator of physiologic and pathologic anglogenesis, vascular endothelial growth factor (VEGF) triggers growth, survival, and migration of leukemia and multiple myeloma cells; plays a pivotal role in hematopolesis; inhibits maturation of dendritic cells; and increases osteoclastic bone-resorbing activity as well as osteoclast chemotaxis. Dysregulation of VEGF expression and signaling pathways therefore plays an important role in the pathogenesis and clinical features of hematologic malignancies, in particular multiple myeloma. Direct and indirect targeting of VEGF and its receptors therefore may provide a Potent novel therapeutic approach to overcome resistance to therapies and thereby improve patient outcome. (C) 2005 by The American Society of Hematology. 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, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [R0-1 CA50945, IP50 CA100707]; PHS HHS [P0-1 78378] NR 292 TC 210 Z9 235 U1 1 U2 6 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 FEB 15 PY 2005 VL 105 IS 4 BP 1383 EP 1395 DI 10.1182/blood-2004-07-2909 PG 13 WC Hematology SC Hematology GA 896YP UT WOS:000226970800012 PM 15471951 ER PT J AU Oh, H Loberiza, FR Zhang, MJ Ringden, O Akiyama, H Asai, T Miyawaki, S Okamoto, S Horowitz, MM Antin, JH Bashey, A Bird, JM Carabasi, MH Fay, JW Gale, RP Giller, RH Goldman, JM Hale, GA Harris, RE Henslee-Downey, J Kolb, HJ Litzow, MR McCarthy, PL Neudorf, SM Serna, DS Socie, G Tiberghien, P Barrett, AJ AF Oh, H Loberiza, FR Zhang, MJ Ringden, O Akiyama, H Asai, T Miyawaki, S Okamoto, S Horowitz, MM Antin, JH Bashey, A Bird, JM Carabasi, MH Fay, JW Gale, RP Giller, RH Goldman, JM Hale, GA Harris, RE Henslee-Downey, J Kolb, HJ Litzow, MR McCarthy, PL Neudorf, SM Serna, DS Socie, G Tiberghien, P Barrett, AJ TI Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; RISK-FACTORS; JAPANESE; ANTIGEN; ASSOCIATION AB The association of ethnicity with the incidence of graft-versus-host disease (GVHD) and other clinical outcomes after transplantation is controversial. We compared the results of HLA-identical sibling bone marrow transplantations for leukemia, performed between 1990 and 1999, among different ethnic populations, including 562 Japanese, 829 white Americans, 71 African Americans, 195 Scandinavians, and 95 Irish. Results for adults and children were analyzed separately. Multivariate analyses of adult patients showed that white Americans, African Americans, and Irish cohorts were at significantly higher risk for acute GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P < .001; RR = 1.84, P < .006; R R = 2.22, P < .001, respectively). White Americans, African Americans, and Irish, but not Scandinavians, were at significantly higher risk for early (within 3 months of transplantation) transplant-related mortality (TRM) compared with Japanese (RR = 2.99, P < .001; RR = 5.88, P < .001; RR = 2.66, P < .009, respectively). No differences in the risk for chronic GVHD, relapse, and overall survival were noted. In the pediatric cohort (limited to Japanese and white Americans), white Americans were at significantly higher risk for acute (RR = 1.93; P = .04) and chronic (RR = 3.16; P = .002) GVHD. No differences in other clinical outcomes were noted. Our findings suggest that ethnicity may influence the risk for GVHD, though overall survival rates after transplantation remain similar. (C) 2005 by The American Society of Hematology. C1 INOUE Mem Hosp, Chuo Ku, Chiba 2600027, Japan. Med Coll Wisconsin, Hlth Policy Inst, IBMTR, GVHD Imune Reconstitut Working Comm, Milwaukee, WI 53226 USA. Huddinge Univ Hosp, S-14186 Huddinge, Sweden. Tokyo Metropolitan Komagome Hosp, Japan Adult Leukemia Study Grp, Tokyo, Japan. Chiba Uiv Hosp, Chuo Ku, Chiba, Japan. Saiseikai Maebashi Hosp, Maebashi, Gumma, Japan. Keio Univ, Sch Med, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Southmead Gen Hosp, Bristol, Avon, England. Univ So Calif, Norris Cotton Canc Ctr, Los Angeles, CA USA. Baylor Univ, Med Ctr, Dallas, TX USA. Ctr Adv Studies Leukemia, Los Angeles, CA USA. Childrens Hosp, Denver, CO 80218 USA. Hammersmith Hosp, London, England. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Childrens Hosp Orange Cty, Orange, CA 92668 USA. Hop St Louis, Paris, France. INSERM, U645, Estab Francais Sang, Besancon, France. RP Oh, H (reprint author), INOUE Mem Hosp, Chuo Ku, 1-16,Shindencho, Chiba 2600027, Japan. EM hakumei@chive.ocn.ne.jp FU NCI NIH HHS [U24-CA76518] NR 23 TC 86 Z9 88 U1 1 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 FEB 15 PY 2005 VL 105 IS 4 BP 1408 EP 1416 DI 10.1182/blood-2004-06-2385 PG 9 WC Hematology SC Hematology GA 896YP UT WOS:000226970800016 PM 15486071 ER PT J AU Kim, JH Chu, SC Gramlich, JL Pride, YB Babendreier, E Chauhan, D Salgia, R Podar, K Griffin, JD Sattler, M AF Kim, JH Chu, SC Gramlich, JL Pride, YB Babendreier, E Chauhan, D Salgia, R Podar, K Griffin, JD Sattler, M TI Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species SO BLOOD LA English DT Article ID GLUCOSE-TRANSPORT; REDOX REGULATION; TYROSINE KINASE; CELL-LINE; PHOSPHATIDYLINOSITOL 3-KINASE; REVERSIBLE INACTIVATION; SIGNAL-TRANSDUCTION; GROWTH-FACTORS; TRANSFORMATION; BCR/ABL AB BCR-ABL oncoprotein-expressing cells are associated with a relative increase of intracellular reactive oxygen species (ROS), which is thought to play a role in transformation. Elevated ROS levels in BCR-ABL-transformed cells were found to be blocked by the mitochondrial complex I inhibitor rotenone as well as the glucose transport inhibitor phloretin, suggesting that the source of increased ROS might be related to increased glucose metabolism. The glucose analog 2-deoxy-glucose (2-DOG) reduced ROS to levels found in non-BCR-ABL-transformed cells and inhibited cell growth alone or in cooperation with imatinib mesylate (Gleevec). A mutant of BCR-ABL that is defective in transformation of myeloid cells, Tyr177Phe, was also found to be defective in raising intracellular ROS levels. Glucose metabolism in BCR-ABL-transformed cells is likely to be mediated by activation of the phosphatidylinositol-3'-kinase (PI3K) pathway, which is regulated through this site. Inhibition of PI3K or mTOR led to a significant decrease in ROS levels. Over- all, our results suggest that elevated levels of ROS in BCR-ABL-transformed cells are secondary to a transformation-associated increase in glucose metabolism and an overactive mitochondrial electron transport chain and is specifically regulated by PI3K. Finally, these results hint at novel targets for drug development that may aid traditional therapy. (C) 2005 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. Univ Chicago, Pritzker Sch Med, Dept Med, Chicago, IL 60637 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM martin_sattler@dfci.harvard.edu FU NIDDK NIH HHS [DK66996] NR 32 TC 126 Z9 130 U1 1 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 FEB 15 PY 2005 VL 105 IS 4 BP 1717 EP 1723 DI 10.1182/blood-2004-03-0849 PG 7 WC Hematology SC Hematology GA 896YP UT WOS:000226970800056 PM 15486067 ER PT J AU Alyea, EP Kim, HT Ho, V Cutler, C Gribben, J DeAngelo, DJ Lee, SJ Windawi, S Ritz, J Stone, RM Antin, JH Soiffer, RJ AF Alyea, EP Kim, HT Ho, V Cutler, C Gribben, J DeAngelo, DJ Lee, SJ Windawi, S Ritz, J Stone, RM Antin, JH Soiffer, RJ TI Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; FUNGAL-INFECTIONS; UNRELATED-DONOR; MATCHED CONTROL; CHEMOTHERAPY; THERAPY; ADULTS; MALIGNANCIES; CYTOGENETICS AB Nonmyeloablative stem cell transplantation (NST) is increasingly used in older patients. The impact of the shift from myeloalblative transplantation to NST on relapse, transplant complications, and outcome has yet to be fully examined. We performed a retrospective analysis of 152 patients older than 50 years undergoing NST or myeloalblative transplantation. Seventy-one patients received nonmyeloablative conditioning, fludarabine (30 mg/m(2)/d x 4) and intravenous busulfan (0.8 mg/kg/d x 4); 81 patients received myeloablative conditioning, primarily cyclophosphamide and total body irradiation. NST patients were more likely to have unrelated donors (58%, versus 36%; P =.009), a prior transplant (25% versus 4%; P = < .0001), and active disease at transplantation (85% versus 59%; P = < .001). Despite the adverse characteristics, overall survival was improved in the NST group at 1 year (51% versus 39%) and 2 years (39% versus 29%; P =.056). There was no difference in progression-free survival (2 years, 27% versus 25%; P =.24). The incidence of grade 2 to 4 graft-versus- host disease was similar (28% versus 270%). The nonrelapse mortality rate was lower for NST patients (32% versus 50%; P = .01), but the relapse rate was higher (46% versus 30%; P = .052). Our experience suggests that, in patients over age 50, NST with fludarabine and low-dose busulfan leads to an overall outcome at least as good as that following myeloablative therapy. (C) 2005 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM edwin_alyea@dfci.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NHLBI NIH HHS [P01 HL070149] NR 24 TC 201 Z9 212 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2005 VL 105 IS 4 BP 1810 EP 1814 DI 10.1182/blood-2004-05-1947 PG 5 WC Hematology SC Hematology GA 896YP UT WOS:000226970800068 PM 15459007 ER PT J AU Leykin, I Hao, K Cheng, JS Meyer, N Pollak, MR Smith, RJH Wong, WH Rosenow, C Li, C AF Leykin, I Hao, K Cheng, JS Meyer, N Pollak, MR Smith, RJH Wong, WH Rosenow, C Li, C TI Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data SO BMC GENETICS LA English DT Article ID GENOTYPING ERRORS; MUTATIONS; PROGRAM; TRAITS; ASSAY; MAPS AB Background: The identification of disease-associated genes using single nucleotide polymorphisms ( SNPs) has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. However, the analysis of such datasets is nontrivial because of the large number of markers, and visualizing the linkage scores in the context of genome maps remains less automated using the current linkage analysis software packages. For example, the haplotyping results are commonly represented in the text format. Results: Here we report the development of a novel software tool called CompareLinkage for automated formatting of the Affymetrix Mapping 10 K genotype data into the "Linkage" format and the subsequent analysis with multi-point linkage software programs such as Merlin and Allegro. The new software has the ability to visualize the results for all these programs in dChip in the context of genome annotations and cytoband information. In addition we implemented a variant of the Lander-Green algorithm in the dChipLinkage module of dChip software ( V1.3) to perform parametric linkage analysis and haplotyping of SNP array data. These functions are integrated with the existing modules of dChip to visualize SNP genotype data together with LOD score curves. We have analyzed three families with recessive and dominant diseases using the new software programs and the comparison results are presented and discussed. Conclusions: The CompareLinkage and dChipLinkage software packages are freely available. They provide the visualization tools for high-density oligonucleotide SNP array data, as well as the automated functions for formatting SNP array data for the linkage analysis programs Merlin and Allegro and calling these programs for linkage analysis. The results can be visualized in dChip in the context of genes and cytobands. In addition, a variant of the Lander-Green algorithm is provided that allows parametric linkage analysis and haplotyping. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Illinois, Dept Comp Sci, Chicago, IL 60607 USA. Univ Iowa, Mol Otolaryngol Res Labs, Iowa City, IA 52242 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. RP Rosenow, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM ileykin@hsph.harvard.edu; khao@hsph.harvard.edu; cjsuicedu@yahoo.com; nicmeyer@uiowa.edu; mpollak@rics.bwh.harvard.edu; richard-smith@uiowa.edu; wwong@hsph.harvard.edu; crosenow@rocketmail.com; cli@hsph.harvard.edu FU NCI NIH HHS [P20 CA096470, P20-CA96470]; NHGRI NIH HHS [R01 HG002341, 1R01HG02341]; NIDCD NIH HHS [R01 DC002842, R01-DC02842]; NIDDK NIH HHS [DK54931, R01 DK054931, R56 DK054931] NR 21 TC 18 Z9 19 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD FEB 15 PY 2005 VL 6 AR 7 DI 10.1186/1471-2156-6-7 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 901XX UT WOS:000227316700001 PM 15713228 ER PT J AU Chung, RT AF Chung, RT TI Cytokine polymorphisms and hepatocellular carcinoma - To B or not to B SO CANCER LA English DT Editorial Material ID HEPATITIS-B; VIRUS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org NR 7 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2005 VL 103 IS 4 BP 654 EP 656 DI 10.1002/CNCR.20837 PG 3 WC Oncology SC Oncology GA 894NF UT WOS:000226797900002 PM 15641028 ER PT J AU Bland, LB Garzotto, M DeLoughery, TG Ryan, CW Schuff, KG Wersinger, EM Lemmon, D Beer, TM AF Bland, LB Garzotto, M DeLoughery, TG Ryan, CW Schuff, KG Wersinger, EM Lemmon, D Beer, TM TI Phase II study of transdermal estradiol in androgen-independent prostate carcinoma SO CANCER LA English DT Article DE prostate carcinoma; estradiol; estrogen; hormonal therapy; transdermal ID HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; PARENTERAL ESTROGEN; VENOUS THROMBOEMBOLISM; ORAL-CONTRACEPTIVES; CLINICAL-TRIALS; PROTEIN-C; CANCER; DIETHYLSTILBESTROL; SERUM AB BACKGROUND. oral estrogen therapy has activity in patients with hormone-naive and androgen-independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids "first pass" liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy oil hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC. METHODS. Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24-hour patches replaced every 7 days). Serum prostate-specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals. RESULTS. Three of 24 patients (12.5%; 95% confidence interval [Cl], 0-26%) had a confirmed PSA reduction > 50%. The Kaplan-Meier estimate of median time to disease progression was 12 weeks (95% Cl, 4.6-19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (+/-95% Cl) serum estradiol level increased from 17.2 pg.mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL (range, 334.6-586.7 pg/mL). The total testosterone level remained stable ill the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed. CONCLUSIONS. in patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors. (C) 2005 American Cancer Society. C1 Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Div Endocrinol & Metab, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Urol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code Cr-145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu FU NCRR NIH HHS [5 M01 RR00334] NR 28 TC 32 Z9 33 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2005 VL 103 IS 4 BP 717 EP 723 DI 10.1002/cncr.20857 PG 7 WC Oncology SC Oncology GA 894NF UT WOS:000226797900011 PM 15641029 ER PT J AU Rodriguez-Galindo, C Wofford, M Castleberry, RP Swanson, GP London, WB Fontanesi, J Pappo, AS Douglass, EC AF Rodriguez-Galindo, C Wofford, M Castleberry, RP Swanson, GP London, WB Fontanesi, J Pappo, AS Douglass, EC TI Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma - Results of pediatric oncology group (Now children's oncology group) study 9486 SO CANCER LA English DT Article DE radiotherapy; chemotherapy; nasopharyngeal carcinoma; pediatric patients ID BARR-VIRUS DNA; PROGRESSION-FREE SURVIVAL; III RANDOMIZED-TRIAL; NEOADJUVANT CHEMOTHERAPY; RETROSPECTIVE ANALYSIS; QUANTITATIVE-ANALYSIS; RADIATION-THERAPY; PLUS RADIOTHERAPY; NECK-CANCER; PHASE-II AB BACKGROUND. Nasopharyngeal carcinoma (NPC) is rare in children, accounting for < 1% of all cases. Treatment most commonly includes radiotherapy but long-term side effects of such treatment can produce devastating cosmetic and functional sequelae in children. Chemotherapy may help to decrease the radiotherapy dose and limit the side effects of local therapies. However, little is known regarding the chemosensitivity of NPC tumors in pediatric patients. METHODS. Patients with American Joint Committee on Cancer (AJCC) Stage I/II disease (Stratum 01) received irradiation only. Patients with AJCC Stage III/IV disease (Stratum 02) received 4 courses of preradiation chemotherapy comprising methotrexate (120 mg/m(2)) on Day 1, with cisplatin (100 mg/m(2)) 24 hours later, 5-fluorouracil 1000 mg/m(2) per day as a continuous infusion for 3 days, and leucovorin 25 mg/m' every 6 hours for 6 doses. Irradiation was given after chemotherapy and consisted of 50.4 gray (Gy) to the upper neck and 45.0 Gy to the lower neck, with a boost to the primary tumor and positive lymph nodes for a total dose of 61.2 Gy. RESULTS. one patient was enrolled in Stratum 01 and 16 evaluable patients were enrolled in Stratum 02. The median age of the patients was 13 years and 65% of the patients were black. All patients tested had evidence of Epstein-Barr virus infection. Two-thirds of the patients developed Grade 3-4 mucositis during chemotherapy. The overall response rate to induction chemotherapy was 93.7%. The overall 4-year event-free and overall survival rates (+/- the standard error) were 77% +/- 12% and 75% +/-, 12%, respectively. CONCLUSIONS. The current study demonstrated that childhood NPC was sensitive to chemotherapy and that chemotherapy before irradiation was feasible. Future trials should investigate equivalent efficacy with a reduced radiotherapy dose. (C) 2005 American Cancer Society. C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. Wake Forest Univ, Sch Med, Dept Pediat Hematol Oncol, Winston Salem, NC 27109 USA. Univ Alabama Birmingham, Childrens Hosp, Dept Hematol Oncol, Birmingham, AL USA. Deaconess Med Ctr, Dept Radiat Oncol, Spokane, WA USA. Univ Florida, Dept Stat, Childrens Oncol Grp, Gainesville, FL 32611 USA. Univ Mississippi, Med Ctr, Dept Radiat Oncol, Jackson, MS 39216 USA. Hosp Sick Children, Dept Hematol Oncol, Toronto, ON M5G 1X8, Canada. AstraZeneca, Wilmington, DE USA. RP Rodriguez-Galindo, C (reprint author), St Jude Childrens Res Hosp, Dept Hematol Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM carlos.rodriguez-galindo@stjude.org NR 55 TC 35 Z9 36 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 15 PY 2005 VL 103 IS 4 BP 850 EP 857 DI 10.1002/cncr.20823 PG 8 WC Oncology SC Oncology GA 894NF UT WOS:000226797900027 PM 15641027 ER PT J AU Ma, PC Jagadeeswaran, R Jagadeesh, S Tretiakova, MS Nallasura, V Fox, EA Hansen, M Schaefer, E Naoki, K Lader, A Richards, W Sugarbaker, D Husain, AN Christensen, JG Salgia, R AF Ma, PC Jagadeeswaran, R Jagadeesh, S Tretiakova, MS Nallasura, V Fox, EA Hansen, M Schaefer, E Naoki, K Lader, A Richards, W Sugarbaker, D Husain, AN Christensen, JG Salgia, R TI Functional expression and mutations of c-met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; PAPILLARY RENAL-CARCINOMAS; DOMAIN BINDING-SITE; TYROSINE KINASE; JUXTAMEMBRANE DOMAIN; SOMATIC MUTATIONS; FACTOR RECEPTOR; SEMA DOMAIN; GEFITINIB; OVEREXPRESSION AB Non-small cell lung cancer (NSCLC) is a difficult disease to treat. The c-Met receptor is an attractive potential target for novel therapeutic inhibition in human cancers. We provide strong evidence that c-Met is overexpressed, activated, and sometimes mutated in NSCLC cell lines and tumor tissues. Expression of c-Met was found in all (100%) of the NSCLC tumor tissues examined (n = 23) and most (89%) of the cell lines (n = 9). Sixty-one percent of tumor tissues strongly expressed total c-Met, especially adenocarcinoma (67%). Specific expression of phospho-Met (p-Met) [Y1003] and [Y1230/1234/1235] was seen by immunohistochemistry. p-Met expression was preferentially observed at the NSCLC tumor invasive fronts. c-Met alterations were identified within the semaphorin domain (E168D, L299F, S323G, and N375S) and the juxtamembrane domain (R988C, R988C + T1010I, S1058P, and alternative splice product skipping entire juxtamembrane domain) of a NSCLC cell line and adenocarcinoma tissues. We validated c-Met as potential therapeutic target using small interfering RNA down-regulation of the receptor expression by 50% to 60% in NSCLC cells. This led to inhibition of p-Met and phospho-AKT and up to 57.1 +/- 7.2% cell viability inhibition at 72 hours. The selective small molecule inhibitor of c-Met SU11274 inhibited cell viability in c-Met-expressing NSCLC cells. SU11274 also abrogated hepatocyte growth factor-induced phosphorylation of c-Met and its downstream signaling. Here, we pro-Ode first direct evidence by small interfering RNA targeting and small molecule inhibitor that c-Met is important in NSCLC biology and biochemistry. These results indicate that c-Met inhibition will be an important therapeutic strategy against NSCLC to improve its clinical outcome. C1 Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect,Pritzker Sch Med, Chicago, IL 60637 USA. Univ Chicago, Med Ctr, Dept Pathol, Pritzker Sch Med, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Mol Diagnost, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Pfizer Inc, Res Pharmacol, San Diego, CA USA. BioSource Int Inc, Camarillo, CA USA. RP Salgia, R (reprint author), Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect,Pritzker Sch Med, 5841 S Maryland Ave,MC2115, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu RI Nallasura, Vidya/D-8947-2011; Jagadeeswaran, Ramasamy/C-9987-2013 NR 46 TC 301 Z9 312 U1 2 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2005 VL 65 IS 4 BP 1479 EP 1488 DI 10.1158/0008-5472.CAN-04-2650 PG 10 WC Oncology SC Oncology GA 897IR UT WOS:000226997800045 PM 15735036 ER PT J AU Liu, RB Varghese, S Rabkin, SD AF Liu, RB Varghese, S Rabkin, SD TI Oncolytic herpes simplex virus vector therapy of breast cancer in C3(1)/SV40 T-antigen transgenic mice SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; REPLICATION-CONDITIONAL HSV; MOUSE MODEL; MAMMARY ADENOCARCINOMA; ANTITUMOR IMMUNITY; SPONTANEOUS TUMORIGENESIS; VIRAL THERAPY; TUMOR-GROWTH; COMPETENT; INTERLEUKIN-12 AB Oncolytic herpes simplex virus vectors are a promising strategy for cancer therapy, as direct cytotoxic agents, inducers of antitumor immune responses, and as expressers of anticancer genes. Progress is dependent upon representative preclinical models to evaluate therapy. In this study, two families of oncolytic herpes simplex virus vectors (G207 and NV1020 series) that have been in clinical trials were examined for the treatment of breast cancer, using the C3(1)/T-Ag transgenic mouse model. Female mice spontaneously develop mammary carcinomas, and the C3(1)/T-Ag-derived tumor cell line M6c forms implantable tumors. Both in vitro and in vivo, G47Delta, derived from G207 by deletion of ICP47 and the US11 promoter, was more efficacious than G207. Whereas NV1023, derived from NV1020 by deletion of ICP47 and insertion of LacZ, was as cytotoxic to M6c cells in vitro as G47Delta, it did not inhibit the growth of s.c. M6c tumors but did extend the survival of intracerebral tumor bearing mice. In contrast, NV1042, NV1023 expressing interleukin 12, inhibited s.c. M6c tumor growth to a similar extent as G47Delta, but was less effective than NV1023 in intracerebral tumors. In the spontaneously arising mammary tumor model, when only the first arising tumor per mouse was treated, G47Delta inhibited the growth of a subset of tumors, and when all tumors were treated, G47Delta significantly delayed tumor progression. When the first mammary tumor was treated and the remaining mammary glands removed, NV1042 was more efficacious than G47Delta at inhibiting the growth and progression of injected tumors. C1 Massachusetts Gen Hosp East, Mol Neurosurg Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp East, Mol Neurosurg Lab, 13th St,Bldg 149,Box 17, Charlestown, MA 02129 USA. EM rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 65 TC 31 Z9 36 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2005 VL 65 IS 4 BP 1532 EP 1540 DI 10.1158/0008-5472.CAN-04-3353 PG 9 WC Oncology SC Oncology GA 897IR UT WOS:000226997800051 PM 15735042 ER PT J AU Spertus, JA Nerella, R Kettlekamp, R House, J Marso, S Borkon, AM Rumsfeld, JS AF Spertus, JA Nerella, R Kettlekamp, R House, J Marso, S Borkon, AM Rumsfeld, JS TI Risk of restenosis and health status outcomes for patients undergoing percutaneous coronary intervention versus coronary artery bypass graft surgery SO CIRCULATION LA English DT Article DE angioplasty; bypass; restenosis; quality of life ID QUALITY-OF-LIFE; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ANGINA RITA TRIAL; ACC/AHA GUIDELINES; FUNCTIONAL STATUS; AMERICAN-COLLEGE; ELUTING STENT; ANGIOPLASTY; DISEASE AB Background - Previous comparisons of percutaneous coronary interventions (PCIs) and coronary artery bypass graft (CABG) surgery have demonstrated similar survival but have also generally found better health status outcomes ( symptoms, function, and quality of life) with CABG. The principal limitation of PCI has been the occurrence of restenosis. No previous studies comparing the health status outcomes of PCI and CABG have examined differences in these outcomes as a function of patients' preprocedural risk for restenosis. Methods and Results - We examined the health status outcomes, using the Seattle Angina Questionnaire (SAQ), among 1459 consecutive patients ( 1027 treated with PCI and 432, with CABG), stratified by their risk for restenosis. In multivariable- adjusted, linear regression analyses, no differences in 1-year angina or quality of life were observed among the 37.4% of patients at low risk for restenosis. However, among the 46.7% at intermediate risk for restenosis, 1-year health status scores were moderately better after CABG surgery compared with PCI ( difference in SAQ angina frequency scores favoring CABG = 6.1 +/- 1.7 points, P = 0.0003; difference in SAQ quality of life = 5.8 +/- 1.6 points, P = 0.0004). Even larger differences in 1-year outcomes favoring CABG surgery were observed in patients at high risk for restenosis ( SAQ angina frequency difference = 10.8 +/- 4.2, P = 0.01; SAQ quality of life difference = 10.8 +/- 3.9, P = 0.006). Conclusions - The relative health status benefits of CABG surgery compared with PCI increase as the risk of restenosis increases. Although selecting CABG or PCI is complex, preprocedural restenosis risk should be considered. It should also be tested as a means for considering drug-eluting as opposed to bare metal stents in PCI. C1 Univ Missouri, Kansas City, MO 64110 USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Denver VA Med Ctr, Denver, CO USA. RP Spertus, JA (reprint author), Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM spertusj@umkc.edu NR 29 TC 30 Z9 32 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 FEB 15 PY 2005 VL 111 IS 6 BP 768 EP 773 DI 10.1161/01.CIR.0000155242.70417.60 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 897MH UT WOS:000227007800010 PM 15699258 ER PT J AU Isselbacher, EM AF Isselbacher, EM TI Thoracic and abdominal aortic aneurysms SO CIRCULATION LA English DT Review DE aneurysm; aorta; diagnosis; imaging; surgery ID RANDOMIZED CONTROLLED-TRIAL; BETA-ADRENERGIC-BLOCKADE; MARFANS-SYNDROME; ANKYLOSING-SPONDYLITIS; ENDOVASCULAR REPAIR; CLINICAL-RELEVANCE; ASCENDING AORTA; ROOT DILATATION; UNITED-STATES; FOLLOW-UP C1 Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, 55 Fruit St,YAW-5A-5800, Boston, MA 02114 USA. EM eisselbacher@partners.org NR 59 TC 294 Z9 314 U1 4 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 2005 VL 111 IS 6 BP 816 EP 828 DI 10.1161/01.CIR.0000154569.08857.7A PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 897MH UT WOS:000227007800017 PM 15710776 ER PT J AU Suk, R Gurubhagavatula, S Park, S Zhou, W Su, L Lynch, TJ Wain, JC Neuberg, D Liu, G Christiani, DC AF Suk, R Gurubhagavatula, S Park, S Zhou, W Su, L Lynch, TJ Wain, JC Neuberg, D Liu, G Christiani, DC TI Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; MESSENGER-RNA LEVELS; FLUOROURACIL CHEMOTHERAPY; GENETIC POLYMORPHISMS; RISK; CISPLATIN; EXPRESSION; SURVIVAL; ASSOCIATION; CARCINOMA AB Purpose: ERCC1 is a lead enzyme in the nucleotide excision repair pathway of DNA repair. Polymorphisms have been identified in the ERCC1 gene, the C8092A and codon 118 polymorphisms, which may lead to an altered capacity to regenerate damaged normal tissue and greater treatment-related toxicity. Experimental Design: Using logistic regression models, we evaluated the ERCC1 C8092A and codon 118 pollymorphisms and their association with the occurrence of grade 3 or 4 toxicity in 214 stage III and IV non-small cell lung cancer patients treated first line with platinum-based chemotherapy. Adjusting covariates were performance status and type of treatment regimen. Results: There was no statistically significant association between either the C8092A or codon 118 polymorphism and overall or hematologic grade 3 or 4 toxicity. However, carrying at least one variant ERCC1 C8092A allele was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (adjusted odds ratio, 2.33; 95 % confidence interval, 1.07-5.05; P = 0.03). Conclusions: Adjusting for performance status and type of treatment regimen, carrying at least one ERCC1 8092A allele is associated with a > 2-fold increase in grade 3 or 4 gastrointestinal toxicity among platinum-treated non-small cell lung cancer patients. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,I-1407, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA71345, CA092824, CA074386, CA90578] NR 29 TC 81 Z9 92 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 FEB 15 PY 2005 VL 11 IS 4 BP 1534 EP 1538 DI 10.1158/1078-0432.CCR-04-1953 PG 5 WC Oncology SC Oncology GA 901EU UT WOS:000227266600027 PM 15746057 ER PT J AU Bae, J Martinson, JA Klingemann, HG AF Bae, J Martinson, JA Klingemann, HG TI Identification of CD19 and CD20 peptides for induction of antigen-specific CTLs against B-cell malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CYTOTOXIC T-LYMPHOCYTES; MULTIPLE-MYELOMA; MONOCLONAL-ANTIBODIES; DENDRITIC CELLS; LYMPHOPROLIFERATIVE DISORDERS; SUICIDE GENE; HEPATITIS-B; NUDE-MICE AB The purpose of these studies was to develop immunogenic peptides derived from the CD19 and CD20 self-antigens for the induction of antigen-specific CTLs against B-cell malignancies. A total of seven peptides were designed and examined for their HLA-A2.1 affinity and immunogenicity. Of these peptides, we identified two highly immunogenic HLA-A2.1-specific peptides, CD19(150-158) (KLMSPKLYV) and CD20(188-196) (SLFLGILSV), which were capable of inducing peptide-specific CTLs. The CTLs displayed HLA-A2.1-restricted and antigen-specific cytotoxicity against Burkitt's lymphoma, chronic B cell leukemia, and multiple myeloma cell lines. The CD19 or CD20 peptide-specific CTL cytotoxicity was confirmed using HLA-A2.1(+) T2 cells presenting the appropriate peptide. No cytotoxic activity was observed against T2 cells presenting the irrelevant MAGE-3 peptide or T2 cells alone. In addition, the CTLs displayed a significant (P < 0.05) increase in cell proliferation and IFN-gamma secretion ( > 830 ng/mL) following restimulation with HLA-A2.1(+)/CD19(+)/CD20(+) tumor cells. The CTLs also displayed a distinct phenotype consisting of a high percentage of CD69(+)/CD45RO(+) and a low percentage of CD45RA(+)/CCR7(+) CD4(+) or CD8(+) T cells characteristic of effector memory cell population. Cyclic guanosine 3',5'-monophosphate culture conditions using serum-free AIM-V medium containing human AB serum, recombinant human interleukin 2 (Proleukin) and CD3/CD28 Dynabeads were developed resulting in a 35-fold expansion of CD20 peptide-specific CTLs. The expanded CD20-CTLs retained their cytotoxic activity (28-49 %) against the Burkitt's lymphoma cell line. In conclusion, we report here on the identification of novel immunogenic CD19150-158 (KLMSPKLYV) and CD20188-196 (SLFLGILSV) peptides that have immunotherapeutic potentials as peptide vaccines or targeted T-cell therapies for treating B-cell malignancies. C1 Harvard Univ, Ctr Med, Dana Farber Canc Inst, VA Hosp,Dept Med Oncol, Boston, MA 02132 USA. RP Bae, J (reprint author), Harvard Univ, Ctr Med, Dana Farber Canc Inst, VA Hosp,Dept Med Oncol, 1400 VWF Pkwy,Room 2A111,Bldg 3, Boston, MA 02132 USA. EM jooeun_bae@dfci.harvard.edu NR 60 TC 16 Z9 16 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 FEB 15 PY 2005 VL 11 IS 4 BP 1629 EP 1638 DI 10.1158/1078-0432.CCR-04-1612 PG 10 WC Oncology SC Oncology GA 901EU UT WOS:000227266600038 PM 15746068 ER PT J AU Savellano, MD Hasan, T AF Savellano, MD Hasan, T TI Photochemical targeting of epidermal growth factor receptor: A mechanistic study SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY; PHOTODYNAMIC THERAPY; IN-VIVO; PHOTOPHYSICAL PROPERTIES; ANTICANCER THERAPY; BREAST-CANCER; CYTOCHROME-C; BPD-MA; CELLS; MODEL AB Purpose: Photoimmunotherapy may allow target-specific photodynamic destruction of malignancies and may also potentiate anticancer antibody therapies. However, clinical use of either of the two modalities is limited for different reasons. Antibody therapies suffer from being primarily cytostatic and the need for prolonged administration with consequent side effects. In the case of photoimmunotherapy, a major impediment has been the absence of well-characterized photosensitizer immunoconjugates (PIC). In this investigation, we suggest a strategy to overcome these limitations and present the successful targeting of epidermal growth factor receptor (EGFR) using a well-characterized PIC. Experimental Design: The PIC consisted of the EGFR-recognizing chimeric monoclonal antibody, C225, conjugated with a two-branched polyethylene glycol and benzoporphyrin derivative (BPD, Verteporfin). Mechanistic studies included photophysics, phototoxicity, cellular uptake, and catabolism experiments to yield dosimetric parameters. Target cells included two EGFR-overexpressing human cancer cell lines, OVCAR-5 and A-431. Nontarget cells included an EGFR-negative fibroblast cell line, 3T3-NR6, and a monocyte-macrophage cell line, J774. Results: BPD-C225 PICs targeted and photodynamically killed EGFR-overexpressing cells, whereas free BPD exhibited no specificity. On a per mole basis, PICs were less phototoxic than free BPD, but PICs were very selective for target cells, whereas free BPD was not. Phototoxicity of the PICs increased at prolonged incubations. Photodynamic dose calculations indicated that PIC photophysics, photochemistry, catabolism, and subcellular localization were important determinants of PIC phototoxic potency. Conclusions: This study shows the efficacy of EGFR targeting with PIC constructs and suggests approaches to improve PIC designs and targeting strategies for in vivo photoimmunotherapy. The approach offers the possibility of dual effects via antibody-mediated cytostasis and photoimmunotherapy-based cytotoxicity. C1 Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, 40 Blossom St,BAR 314, Boston, MA 02114 USA. EM thasan@partners.org FU NIAMS NIH HHS [R01AR40352] NR 59 TC 51 Z9 52 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 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2005 VL 11 IS 4 BP 1658 EP 1668 DI 10.1158/1078-0432.CCR-04-1902 PG 11 WC Oncology SC Oncology GA 901EU UT WOS:000227266600041 PM 15746071 ER PT J AU Pien, HH Fischman, AJ Thrall, JH Sorensen, AG AF Pien, HH Fischman, AJ Thrall, JH Sorensen, AG TI Using imaging biomarkers to accelerate drug development and clinical trials SO DRUG DISCOVERY TODAY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; ADVANCED COLORECTAL-CANCER; EARLY RHEUMATOID-ARTHRITIS; F-18 LABELED FLUCONAZOLE; CEREBRAL-BLOOD-FLOW; HYPERACUTE STROKE; PHARMACEUTICAL RESEARCH; SURROGATE MARKERS; END-POINTS; CHEMOTHERAPY AB There is increasing evidence that human medical imaging can help answer key questions that arise during the drug development process. Imaging modalities such as magnetic resonance imaging, computed tomography and positron emission tomography can offer significant insights into the bioactivity, pharmacokinetics and dosing of drugs, in addition to supporting registration applications. In this review, examples from oncology, neurology, psychiatry, infectious diseases and inflammatory diseases are used to illustrate the role imaging can play. We conclude with some remarks concerning new developments that will be required to significantly advance the field of pharmaco-imaging. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pien, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM hpien@nmr.mgh.harvard.edu NR 65 TC 56 Z9 59 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD FEB 15 PY 2005 VL 10 IS 4 BP 259 EP 266 AR PII S1359-6446(04)03334-3 DI 10.1016/S1359-6446(04)03334-3 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 896YC UT WOS:000226969500008 PM 15708744 ER PT J AU Liadaki, K Kho, AT Sanoudou, D Schienda, J Flint, A Beggs, AH Kohane, IS Kunkel, LM AF Liadaki, K Kho, AT Sanoudou, D Schienda, J Flint, A Beggs, AH Kohane, IS Kunkel, LM TI Side Population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Side Population cells; Main Population cells; skeletal muscle; bone marrow ID HEMATOPOIETIC STEM-CELLS; BINDING CASSETTE TRANSPORTER; SKELETAL-MUSCLE; IN-VIVO; GENE-EXPRESSION; MUSCULAR-DYSTROPHY; EPH RECEPTORS; MYOGENIC SPECIFICATION; FATE DETERMINATION; MYELOID-LEUKEMIA AB Side Population (SP) cells, isolated from murine adult bone marrow (BM) based on the exclusion of the DNA dye Hoechst 33342, exhibit potent hematopoietic stem cell (HSC) activity when compared to Main Population (MP) cells. Furthermore, SP cells derived from murine skeletal muscle exhibit both hematopoietic and myogenic potential in vivo. The multipotential capacity of SP cells isolated from variable tissues is supported by an increasing number of studies. To investigate whether the SP phenotype is associated with a unique transcriptional profile, we characterized gene expression of SP cells isolated from two biologically distinct tissues, bone marrow and muscle. Comparison of SP cells with differentiated MP cells within a tissue revealed that SP cells are in an active transcriptional and translational status and underexpress genes reflecting tissue-specific functions. Direct comparison of gene expression of SP cells isolated from different tissues identified genes common to SP cells as well as genes specific to SP cells within a particular tissue and further define a muscle and bone marrow environment. This study reports gene expression of muscle SP cells, common features and differences between SP cells isolated from muscle and bone marrow, and further identifies common signaling pathways that might regulate SP cell functions. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Genom Program, Genet Div,Childrens Hosp Boston, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Acad Athens, Div Mol Biol, Fdn Biomed Res, Athens 11527, Greece. RP Kunkel, LM (reprint author), Harvard Univ, Sch Med, Genom Program, Genet Div,Childrens Hosp Boston, 320 Longwood Ave,Enders 570, Boston, MA 02115 USA. EM kunkel@enders.tch.harvard.edu RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Sanoudou, Despina/0000-0003-3704-1941; Beggs, Alan/0000-0001-8818-0568 FU NIAMS NIH HHS [R01 AR44345]; NINDS NIH HHS [P01 NS040828, P01 NS40828] NR 66 TC 26 Z9 27 U1 1 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 15 PY 2005 VL 303 IS 2 BP 360 EP 374 DI 10.1016/j.yexcr.2004.10.011 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 891HL UT WOS:000226571800014 PM 15652349 ER PT J AU Kanellopoulou, C Muljo, SA Kung, AL Ganesan, S Drapkin, R Jenuwein, T Livingston, DM Rajewsky, K AF Kanellopoulou, C Muljo, SA Kung, AL Ganesan, S Drapkin, R Jenuwein, T Livingston, DM Rajewsky, K TI Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing SO GENES & DEVELOPMENT LA English DT Article DE RNA interference; microRNA; heterochromatin silencing; DNA methylation ID DOUBLE-STRANDED-RNA; H3 LYSINE-9 METHYLATION; SHORT INTERFERING RNA; DE-NOVO METHYLATION; DNA METHYLATION; C-ELEGANS; HISTONE H3; DROSOPHILA-MELANOGASTER; MAMMALIAN-CELLS; PERICENTRIC HETEROCHROMATIN AB Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21-25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or translational level. We disrupted the dicer-1 (dcr-1) gene in mouse embryonic stem (ES) cells by conditional gene targeting and generated Dicer-null ES cells. These cells were viable, despite being completely defective in RNA interference (RNAi) and the generation of microRNAs (miRNAs). However, the mutant ES cells displayed severe defects in differentiation both in vitro and in vivo. Epigenctic silencing of centromeric repeat sequences and the expression of homologous small dsRNAs were markedly reduced. Re-expression of Dicer in the knockout cells rescued these phenotypes. Our data suggest that Dicer participates in multiple, fundamental biological processes in a mammalian organism, ranging from stem cell differentiation to the maintenance of centromeric heterochromatin structure and centromeric silencing. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Vienna Bioctr, Res Inst Mol Pathol, A-1030 Vienna, Austria. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu; rajewsky@cbr.med.harvard.edu RI Muljo, Stefan/F-5671-2015; jia, xu/A-8386-2016; Drapkin, Ronny/E-9944-2016; OI Muljo, Stefan/0000-0003-1013-446X; Drapkin, Ronny/0000-0002-6912-6977; Kung, Andrew/0000-0002-9091-488X NR 88 TC 821 Z9 891 U1 2 U2 32 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 15 PY 2005 VL 19 IS 4 BP 489 EP 501 DI 10.1101/gad.1248505 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 899DF UT WOS:000227124400011 PM 15713842 ER PT J AU Vasir, B Avigan, D Wu, Z Crawford, K Turnquist, S Ren, J Kufe, D AF Vasir, B Avigan, D Wu, Z Crawford, K Turnquist, S Ren, J Kufe, D TI Dendritic cells induce MUC1 expression and polarization on human T cells by an IL-7-dependent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; INTERCELLULAR-ADHESION MOLECULE-1; BETA-CATENIN; TANDEM REPEATS; DEFICIENT MICE; IN-VIVO; C-SRC; INTERLEUKIN-7; IL-7; PROLIFERATION AB The MUC1 transmembrane mucin is expressed on the surface of activated human T cells; however, the physiologic signals responsible for the regulation of MUC1 in T cells are not known. The present studies demonstrate that IL-7, but not IL-2 or IL-4, markedly induces MUC1 expression on CD3(+) T cells. MUC1 was also up-regulated by IL-15, but to a lesser extent than that found with IL-7. The results show that IL-7 up-regulates MUC1 on CD4(+), CD8(+), CD25(+), CD69(+), naive CD45RA(+), and memory CD45RO(+) T cells. In concert with induction of MUCI expression by IL-7, activated dendritic cells (DC) that produce IL-7 up-regulate MUC1 on allogeneic CD3(+) T cells. DC also induce MUC1 expression on autologous CD3(+) T cells in the presence of recall Ag. Moreover, DC-induced MUC1 expression on T cells is blocked by a neutralizing anti-IL-7 Ab. The results also demonstrate that DC induce polarization of MUC1 on T cells at sites opposing the DC-T cell synapse. These findings indicate that DC-mediated activation of Ag-specific T cells is associated with induction and polarization of MUC1 expression by an IL-7dependent mechanism. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Room D830, Boston, MA 02115 USA. EM donald-kufe@dfci.harvard.edu FU NCI NIH HHS [CA42802, CA100707] NR 61 TC 17 Z9 18 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 FEB 15 PY 2005 VL 174 IS 4 BP 2376 EP 2386 PG 11 WC Immunology SC Immunology GA 897EL UT WOS:000226986700073 PM 15699174 ER PT J AU Matejuk, A Hopke, C Vandenbark, AA Hurn, PD Offner, H AF Matejuk, A Hopke, C Vandenbark, AA Hurn, PD Offner, H TI Middle-age male mice have increased severity of experimental autoimmune encephalomyelitis and are unresponsive to testosterone therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; MULTIPLE-SCLEROSIS PATIENTS; CD4(+)CD25(+) TREG CELLS; CENTRAL-NERVOUS-SYSTEM; ANDROGEN RECEPTOR; BIOAVAILABLE TESTOSTERONE; SUPPRESSIVE ACTIVITY; LUTEINIZING-HORMONE; CYTOKINE SECRETION; GENDER-DIFFERENCES AB Treatment with sex hormones is known to protect against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, little is known about how age affects the course of EAE or response to hormone treatment. This study demonstrates striking differences between middle-age vs young C57BL/6 male mice in the clinical course of EAE and response to both testosterone (T4) and estrogen (E2) hormone therapy. Unlike young males that developed an acute phase of EAE followed by a partial remission, middle-age males suffered severe chronic and unremitting EAE that was likely influenced by alterations in the distribution and function of splenic immunocytes and a significant reduction in suppressive activity of CD4(+)CD25(+) regulatory T cells in the spleen and spinal cord. Middle-age males had reduced numbers of splenic CD4(+) T cells that were generally hypoproliferative, but enhanced numbers of splenic macrophages and MHC class II-expressing cells, and increased secretion of the proinflammatory factors IFN-gamma and MCP-1. Surprisingly, middle-age males were unresponsive to the EAE-protective effects of T4 and had only a transient benefit from E2 treatment; young males were almost completely protected by both hormone treatments. T4 treatment of young males inhibited proliferation of myelin oligodendrocyte glycoprotein 35-55-specific T cells and secretion of TNF-alpha and IFN-gamma. The effects of T4 in vivo and in vitro were reversed by the androgen receptor antagonist, flutamide, indicating that the regulatory effects of T4 were mediated through the androgen receptor. These data are the first to define age-dependent differences in EAE expression and response to hormone therapy. C1 Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23221, NS23444] NR 64 TC 38 Z9 39 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 FEB 15 PY 2005 VL 174 IS 4 BP 2387 EP 2395 PG 9 WC Immunology SC Immunology GA 897EL UT WOS:000226986700074 PM 15699175 ER PT J AU Matute-Bello, G Liles, WC Frevert, CW Dhanireddy, S Ballman, K Wong, V Green, RR Song, HY Witcher, DR Jakubowski, JA Martin, TR AF Matute-Bello, G Liles, WC Frevert, CW Dhanireddy, S Ballman, K Wong, V Green, RR Song, HY Witcher, DR Jakubowski, JA Martin, TR TI Blockade of the Fas/FasL system improves pneumococcal clearance from the lungs without preventing dissemination of bacteria to the spleen SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 99th International Conference of the American-Thoracic-Society CY MAY 16-23, 2003 CL SEATTLE, WA SP Amer Thorac Soc ID RESPIRATORY-DISTRESS-SYNDROME; EPITHELIAL-CELL APOPTOSIS; NF-KAPPA-B; FAS LIGAND; PULMONARY-FIBROSIS; DECOY RECEPTOR; SOLUBLE FORM; IN-VIVO; ACTIVATION; SEPSIS AB Background. The Fas/FasL system is both proapoptotic and proinflammatory. FasL is inhibited by decoy receptor-3 (DcR3), a naturally occurring decoy receptor. We determined the effects of systemic blockade of the Fas/FasL system by a DcR3 analog (DcR3-a) in mice with pneumococcal pneumonia. Methods. Streptococcus pneumoniae (7.2 x 10(5) or 1.9 x 10(7) cfu/mL) was instilled intratracheally into untreated C57Bl/6 mice, C57Bl/6 mice treated with DcR3-a, or Fas-deficient lpr mice, and the mice were studied 48 h later. Results. After instillation of the lower bacterial dose, disruption of the Fas/FasL system by either DcR3-a or the lpr mutation resulted in improved clearance of bacteria in the lungs (mean +/- SE, and 4.6 +/- 2.1 x 10(6) and 3.5 +/- 1.6 x 10(6) cfu/lung, respectively, vs. 21.9 +/- 9.3 x 10(6) cfu/lung in untreated C57Bl/6 mice; P < .05) and decreased percentage of polymorphonuclear neutrophils in bronchoalveolar lavage fluid (mean &PLUSMN; SE, and 19.3% &PLUSMN; 9.5%, respectively, vs. in untreated C57Bl/ 6 mice;). These changes were associated 20.2% &PLUSMN; 7.8% 55.0% &PLUSMN; 12.2% P < .05 with decreased lung concentrations of the proinflammatory cytokines tumor necrosis factor-alpha and macrophage inflammatory protein-2 and with a decrease in apoptotic cells in the alveolar walls. Conclusion. Blockade of the Fas/FasL system by DcR3-alpha in the lungs improves clearance of bacteria in mice with pneumococcal pneumonia. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Allergy & Infect Med, Seattle, WA USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Matute-Bello, G (reprint author), Seattle VA Med Ctr, 151L,1660 S Columbian Way, Seattle, WA 98108 USA. EM matuteb@u.washington.edu FU NHLBI NIH HHS [HL62995, HL65892, HL70840-01, HL73996] NR 37 TC 26 Z9 26 U1 1 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 FEB 15 PY 2005 VL 191 IS 4 BP 596 EP 606 DI 10.1086/427261 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 888ZM UT WOS:000226413100016 PM 15655784 ER PT J AU Finn, AV Palaclos, IF Kastrati, A Gold, HK AF Finn, AV Palaclos, IF Kastrati, A Gold, HK TI Drug-eluting stents for diabetes mellitus - A rush to judgment? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ARTERIAL-WALL THICKNESS; GLYCEMIC CONTROL; RESTENOSIS; DISEASE; TRIAL; REVASCULARIZATION; IMPACT; ATHEROSCLEROSIS; TROGLITAZONE AB The two pivotal U.S. trials of drug-eluting stents do not establish the principle that these stents are superior to thin-strut bare-metal stents for preventing repeat revascularization in patients with diabetes. Neither study was adequately powered to make this determination. Moreover, both studies used thick-strut stents known to have high restenosis rates as controls. Low angiographic follow-up underestimates the true target lesion revascularization rate in the Polymer-Based Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease (TAXUS-IV) trial because of the high incidence of silent ischemia in patients with diabetes. Optimal therapy for diabetic coronary disease should include a comprehensive approach directed toward metabolic normalization in addition to local stent-based therapy. (C) 2005 by the American College of Cardiology Foundation. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Tech Univ Munich, Med Klin Rechts Der Isar 1, Munich, Germany. Tech Univ Munich, Deutsch Herzzentrum, Munich, Germany. RP Finn, AV (reprint author), Massachusetts Gen Hosp, Cardiac Unit, 55 Fruit St, Boston, MA 02114 USA. NR 24 TC 28 Z9 29 U1 0 U2 2 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 FEB 15 PY 2005 VL 45 IS 4 BP 479 EP 483 DI 10.1016/j.jacc.2004.10.060 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 898US UT WOS:000227102300002 PM 15708689 ER PT J AU Ciesielski, KT Hamalainen, MS Lesnik, PG Geller, DA Ahlfors, SP AF Ciesielski, KT Hamalainen, MS Lesnik, PG Geller, DA Ahlfors, SP TI Increased MEG activation in OCD reflects a compensatory mechanism specific to the phase of a visual working memory task SO NEUROIMAGE LA English DT Review DE obsessive-compulsive disorder; magnetoencephalography; delayed matching-to-sample task; inhibition; retrieval ID OBSESSIVE-COMPULSIVE DISORDER; DORSOLATERAL PREFRONTAL CORTEX; GLUCOSE METABOLIC RATES; EVENT-RELATED FMRI; FRONTAL-LOBE; CORTICAL SURFACE; SYMPTOM PROVOCATION; UNIPOLAR DEPRESSION; COORDINATE SYSTEM; FUNCTIONAL MRI AB We examined spatio-temporal patterns of evoked magnetoencephalographic signals (MEG) in patients with obsessive-compulsive disorder (OCD) during the Encoding, Retention, and Retrieval phases of a Delayed Matching-to-Sample working memory task (DMST). The question was whether the mechanisms of abnormally increased cortical excitability, frequently reported in OCD, relate to a global cortical disinhibition and unselective over-processing of stimuli or, alternatively, to a compensatory mechanism of effortful enhanced inhibitory control. The DMST-related network of activation in OCD was found similar to that of Controls, and to that reported in other neuroimaging studies. The pattern of increased MEG activation in OCD patients was phase specific. During the Encoding phase, the activation was enhanced in the region of anterior insula and reduced in the posterior-inferior parietal cortex. During Retention, the activation was reduced in the occipital, parietal, superior temporal sulcus, and dorsolateral prefrontal cortex (RA 6/8/9). During Retrieval, a significant increase of activation was found in the right anterior insula extending towards the orbital region and right superior temporal sulcus, along with reduced activation in the left parietal cortex. The performance accuracy was high in OCD and comparable to Controls, although the RTs were prolonged. The results are discussed as being consistent with the hypothesis of a compensatory mechanism of effortful inhibitory control. This mechanism may be a major contributor to the increased cortical activation during Encoding and, in particular, Retrieval of the DMST task in patients suffering OCD. The findings do not support the concept of a faulty working memory mechanism per se in OCD. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, MIT,HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Ciesielski, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, MIT,HMS, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM ktc@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; Ahlfors, Seppo/P-3644-2016 FU NCRR NIH HHS [P41RR14075] NR 104 TC 25 Z9 26 U1 9 U2 13 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 FEB 15 PY 2005 VL 24 IS 4 BP 1180 EP 1191 DI 10.1016/j.neuroimage.2004.10.018 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 894JT UT WOS:000226788100027 PM 15670696 ER PT J AU Turner, GM Zacharakis, G Soubret, A Ripoll, J Ntziachristos, V AF Turner, GM Zacharakis, G Soubret, A Ripoll, J Ntziachristos, V TI Complete-angle projection diffuse optical tomography by use of early photons SO OPTICS LETTERS LA English DT Article ID IMAGE-RECONSTRUCTION; TURBID MEDIA; CAMERA; SYSTEM AB We present the first, to our knowledge, experimental images of complex-shaped phantoms embedded in diffuse media by use of optical tomography. Imaging is based on a complete-angle projection tomographic technique that utilizes transmitted early photons. Results are contrasted with measurements obtained at later gates as well as pseudocontinuous-wave data. The scanning system developed employs noncontact illumination and detection technologies that allow for high spatial sampling of transmitted photons. Combining this system with complete-angle illumination is found to be an important strategy toward improved imaging performance, resulting in a better-posed inversion problem. The appropriateness of reconstruction algorithms similar to those employed in x-ray computed tomography are showcased, and suggestions for model improvements are provided. (C) 2005 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion, Crete, Greece. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu RI Zacharakis, Giannis/A-2544-2014; Ripoll, Jorge/J-8134-2012 OI Zacharakis, Giannis/0000-0002-6438-0773; Ripoll, Jorge/0000-0001-8856-7738 FU NIBIB NIH HHS [R01 EB 000750] NR 17 TC 68 Z9 68 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD FEB 15 PY 2005 VL 30 IS 4 BP 409 EP 411 DI 10.1364/OL.30.000409 PG 3 WC Optics SC Optics GA 896HR UT WOS:000226925700021 PM 15762444 ER PT J AU Zarrin, AA Tian, M Wang, J Borjeson, T Alt, FW AF Zarrin, AA Tian, M Wang, J Borjeson, T Alt, FW TI Influence of switch region length on immunoglobulin class switch recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IgH switch region; activation-induced deaminase; synthetic switch region; IgG1 ID CYTIDINE DEAMINASE AID; SOMATIC HYPERMUTATION; REPETITIVE SEQUENCES; DNA DEAMINATION; B-CELLS; TRANSCRIPTION; MECHANISM; BINDING; ENZYME; REPAIR AB The class and effector functions of antibodies are modulated through the process of Ig heavy chain class switch recombination (CSR). CSR occurs between switch (S) regions that lie upstream of the various Ig heavy chain constant region exons. Molecular analyses of S-region functions have been hampered by their large size and repetitive nature. To test potential relationships between S-region size and efficiency of CSR, we generated normal B lymphocytes in which the 12-kb S region flanking the Cgamma1 exons (Sgamma1) was replaced with synthetic or endogenous S regions of various lengths. Replacement of Sgamma1 with 1- and 2-kb synthetic sequences representing the Sgamma1 core repeats or a 4-kb portion of the core endogenous Sgamma1 region supported CSR frequencies that directly correlated with S-region length. These findings indicate that S-region size is an important factor in determining endogenous CSR efficiency. Moreover, these results also will allow the development of a systematic system to test the function of various S-region motifs by replacing endogenous S regions with synthetic S regions controlled for size effects. C1 Harvard Univ, Childrens Hosp, Sch Med,Howard Hughes Med Inst, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med,Howard Hughes Med Inst, CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu RI Wang, Jing/M-7813-2015 OI Wang, Jing/0000-0003-4343-2527 FU NIAID NIH HHS [AI31541, P01 AI031541, U19 AI031541] NR 30 TC 38 Z9 38 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 FEB 15 PY 2005 VL 102 IS 7 BP 2466 EP 2470 DI 10.1073/pnas.0409847102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 898JM UT WOS:000227073100040 PM 15684074 ER PT J AU Rooney, S Alt, FW Sekiguchi, JA Manis, JP AF Rooney, S Alt, FW Sekiguchi, JA Manis, JP TI Artemis-independent functions of DNA-dependent protein kinase in Ig heavy chain class switch recombination and development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ATM; DNA-PKcs ID CYTIDINE DEAMINASE AID; B-CELL DEVELOPMENT; SOMATIC HYPERMUTATION; V(D)J RECOMBINATION; DEFICIENT MICE; GENOMIC INSTABILITY; CATALYTIC SUBUNIT; LIGASE-IV; ATM; END AB Assembly of Ig genes in B lineage cells involves two distinct DNA rearrangements. In early B cell development, site-specific double strand breaks (DSBs) at germ-line V, D, and J gene segments are joined via nonhomologous end-joining (NHEJ) to form variable region exons. Activated mature B cells can change expressed Ig heavy chain constant region exons by class switch recombination (CSR), which also involves DSB intermediates. Absence of any known NHEJ factor severely impairs joining of cleaved V, D, and J segments. In NHEJ, DNA-dependent protein kinase (DNA-PK), which is comprised of the Ku70/80 end-binding heterodimer and the catalytic subunit (DNA-PKcs), activates Artemis to generate a nuclease that processes DSBs before ligation. Because inactivation of DNA-PKcs components also severely affects CSR, we tested whether DNA-PK also functions in CSR via activation of Artemis. To obviate the requirement for V(D)J recombination, we generated DNA-PKcs- and Artemis-deficient B cells that harbored preassembled Ig heavy chain and kappa-light chain "knock-in" (HL) alleles. We found that Artemis-deficient HL B cells undergo robust CSR, indicating that DNA-PKcs functions in CSR via an Artemis-independent mechanism. To further elucidate potential Artemis-independent functions of DNA-PKcs, we asked whether the embryonic lethality associated with double-deficiency for DNA-PKcs and the related ataxia-telangiectasia-mutated (ATM) kinase was also observed in mice doubly deficient for ATM and Artemis. We found that ATM/Artemis double-deficient mice were viable and born in normal Mendelian numbers. Therefore, we conclude that DNA-PKcs has Artemis-independent functions in CSR and normal development. C1 Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NIAID NIH HHS [AI35714, U19 AI031541, P01 AI035714, AI31541, P01 AI031541] NR 58 TC 28 Z9 29 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 FEB 15 PY 2005 VL 102 IS 7 BP 2471 EP 2475 DI 10.1073/pnas.0409857102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 898JM UT WOS:000227073100041 PM 15699324 ER PT J AU Chang, JH Urbach, JM Law, TF Arnold, LW Hu, A Gombar, S Grant, SR Ausubel, FM Dangl, JL AF Chang, JH Urbach, JM Law, TF Arnold, LW Hu, A Gombar, S Grant, SR Ausubel, FM Dangl, JL TI A high-throughput, near-saturating screen for type III effector genes from Pseudomonas syringae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE host-microbe interaction; plant pathogenesis; Arabidopsis; FACS ID PV. TOMATO DC3000; SECRETION SYSTEM EFFECTORS; AVIRULENCE GENES; GENOMEWIDE IDENTIFICATION; PHYTOPATHOGENIC BACTERIA; PATHOGENICITY ISLAND; FUNCTIONAL-ANALYSIS; PLANT-PATHOGENS; SIGMA-FACTOR; HOST-CELLS AB Pseudomonas syringae strains deliver variable numbers of type III effector proteins into plant cells during infection. These proteins are required for virulence, because strains incapable of delivering them are nonpathogenic. We implemented a whole-genome, high-throughput screen for identifying A syringae type III effector genes. The screen relied on FACS and an arabinose-inducible hrpL or factor to automate the identification and cloning of HrpL-regulated genes. We determined whether candidate genes encode type III effector proteins by creating and testing full-length protein fusions to a reporter called Delta79AvrRpt2 that, when fused to known type III effector proteins, is translocated and elicits a hypersensitive response in leaves of Arabidopsis thaliana expressing the RPS2 plant disease resistance protein. Delta79AvrRpt2 is thus a marker for type III secretion system-dependent translocation, the most critical criterion for defining type III effector proteins. We describe our screen and the collection of type III effector proteins from two pathovars of A syringae. This stringent functional criteria defined 29 type III proteins from P. syringae pv. tomato, and 19 from P. syringae pv. phaseolicola race 6. Our data provide full functional annotation of the hrpL-dependent type III effector suites from two sequenced A syringae pathovars and show that type III effector protein suites are highly variable in this pathogen, presumably reflecting the evolutionary selection imposed by the various host plants. C1 Univ N Carolina, Dept Biol CB 3280, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol CB 7290, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Dept Mol Biol, Cambridge, MA 02139 USA. Syngenta Biotechnol Inc, Res Triangle Pk, NC 27709 USA. RP Dangl, JL (reprint author), Univ N Carolina, Dept Biol CB 3280, Chapel Hill, NC 27599 USA. EM dangl@email.unc.edu FU NIGMS NIH HHS [F32 GM020296, R01 GM066025, R01GM066025, F32-GM20296-02S1, R01GM48707, R01 GM048707] NR 40 TC 149 Z9 161 U1 1 U2 26 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 FEB 15 PY 2005 VL 102 IS 7 BP 2549 EP 2554 DI 10.1073/pnas.0409660102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 898JM UT WOS:000227073100055 PM 15701698 ER PT J AU Apidianakis, Y Mindrinos, MN Xiao, WZ Lau, GW Baldini, RL Davis, RW Rahme, LG AF Apidianakis, Y Mindrinos, MN Xiao, WZ Lau, GW Baldini, RL Davis, RW Rahme, LG TI Profiling early infection responses: Pseudomonas aeruginosa eludes host defenses by suppressing antimicrobial peptide gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE innate immunity; pathogenesis; Drosophila melanogaster; immune potentiation ID GENOME-WIDE ANALYSIS; PEPTIDOGLYCAN RECOGNITION PROTEIN; DROSOPHILA-MELANOGASTER; IMMUNE-RESPONSES; CONSTITUTIVE EXPRESSION; TARGET GENES; TOLL; PATHOGENICITY; ACTIVATION; PATHWAYS AB Insights into the host factors and mechanisms mediating the primary host responses after pathogen presentation remain limited, due in part to the complexity and genetic intractability of host systems. Here, we employ the model Drosophila melanogaster to dissect and identify early host responses that function in the initiation and progression of Pseudomonas aeruginosa pathogenesis. First, we use immune potentiation and genetic studies to demonstrate that flies mount a heightened defense against the highly virulent P. aeruginosa strain PA14 when first inoculated with strain CF5, which is avirulent in flies; this effect is mediated via the lmd and Toll signaling pathways. Second, we use whole-genome expression profiling to assess and compare the Drosophila early defense responses triggered by the PA14 vs. CF5 strains to identify genes whose expression patterns are different in susceptible vs. resistant host-pathogen interactions, respectively. Our results identify pathogenesis- and defense-specific genes and uncover a previously undescribed mechanism used by A aeruginosa in the initial stages of its host interaction: suppression of Drosophila defense responses by limiting antimicrobial peptide gene expression. These results provide insights into the genetic factors that mediate or restrict pathogenesis during the early stages of the bacterial-host interaction to advance our understanding of P. aeruginosa-human infections. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Rahme, LG (reprint author), Massachusetts Gen Hosp, Dept Surg, Wellman 340,50 Blossom St, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu RI Baldini, Regina/C-4035-2012; OI Baldini, Regina/0000-0003-4349-6352; Apidianakis, Yiorgos/0000-0002-7465-3560 NR 40 TC 97 Z9 99 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 15 PY 2005 VL 102 IS 7 BP 2573 EP 2578 DI 10.1073/pnas.0409588102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 898JM UT WOS:000227073100059 PM 15695583 ER PT J AU Zhou, XH Qin, GS AF Zhou, XH Qin, GS TI Improved confidence intervals for the sensitivity at a fixed level of specificity of a continuous-scale diagnostic test SO STATISTICS IN MEDICINE LA English DT Article DE binomial proportion; sensitivity; specificity; diagnostic accuracy; bootstrap method; confidence intervals AB For a continuous-scale diagnostic test, it is of interest to construct a confidence interval for the sensitivity of the diagnostic test at the cut-off that yields a predetermined level of its specificity (for example. 80, 90 or 95 per cent). In this paper we propose two new intervals for the sensitivity of a continuous-scale diagnostic test at a fixed level of specificity. We then conduct simulation studies to compare the relative performance of these two intervals with the best existing BCa bootstrap interval, proposed by Plan et al. Our simulation results show that the newly proposed intervals are better than the BCa bootstrap interval in terms of covet-age accuracy and interval length. Copyright (C) 2005 John Wiley Sons. Ltd. C1 Vet Affairs Puget Sound Hlth Care Syst, Biostat Unit, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Georgia State Univ, Dept Math & Stat, Atlanta, GA 30302 USA. RP Zhou, XH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Biostat Unit, Hlth Serv Res & Dev Ctr Excellence, Bldg 1,Rm 424,1660 S Columbian Way, Seattle, WA 98108 USA. EM azhou@u.washington.edu NR 10 TC 24 Z9 24 U1 1 U2 5 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 FEB 15 PY 2005 VL 24 IS 3 BP 465 EP 477 DI 10.1002/sim.1563 PG 13 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 892OE UT WOS:000226659100009 PM 15635678 ER PT J AU O'Quigley, J Xu, RH Stare, J AF O'Quigley, J Xu, RH Stare, J TI Explained randomness in proportional hazards models SO STATISTICS IN MEDICINE LA English DT Article DE correlation; explained randomness; information gain; proportional hazards ID DEPENDENCE; REGRESSION AB A coefficient of explained randomness, analogous to explained variation but for non-linear models, was presented by Kent. The construct hinges upon the notion of Kullback-Leibler information gain. Kent and O'Quigley developed these ideas, obtaining simple, multiple and partial coefficients for the situation of proportional hazards regression. Their approach was based upon the idea of transforming a general proportional hazards model to a specific one of Weibull form. Xu and O'Quigley developed a more direct approach, more in harmony with the semi-parametric nature of the proportional hazards model thereby simplifying inference and allowing, for instance. the use of time dependent covariates. A potential drawback to the coefficient of Xu and O'Quigley is its interpretation as explained randomness in the covariate given time. An investigator might feel that the interpretation of the Kent and O'Quigley coefficient, as a proportion of explained randomness of time given the covariate, is preferable. One purpose of this note is to indicate that, under an independent censoring assumption, the two population coefficients coincide. Thus the simpler inferential setting for Xu and O'Quigley can also be applied to the coefficient of Kent and O'Quigley. Our second purpose is to point out that a sample-based coefficient in common use in the SAS statistical package can be interpreted as an estimate of explained randomness when there is no censoring. When there is censoring the SAS coefficient would not seem satisfactory, in that its population counterpart depends on an independent censoring mechanism. However there is a quick fix and we argue in favour of its use. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Ljubljana, Sch Med, Dept Biomed Informat, Ljubljana, Slovenia. RP Xu, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM joq@biomath.jussieu.fr; rxu@jimmy.harvard.edu; janez.stare@mf.uni-lj.si RI O'Quigley, John/E-2073-2017 NR 13 TC 50 Z9 50 U1 0 U2 1 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 FEB 15 PY 2005 VL 24 IS 3 BP 479 EP 489 DI 10.1002/sim.1946 PG 11 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 892OE UT WOS:000226659100010 PM 15532086 ER PT J AU Sykes, M Shimizu, I Kawahara, T AF Sykes, M Shimizu, I Kawahara, T TI Mixed hematopoietic chimerism for the simultaneous induction of T and B cell tolerance SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 4th Beaune Seminar in Transplant Research CY JUN 03-04, 2004 CL Beaune, FRANCE ID ANTIBODY-PRODUCING CELLS; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; GAL-ALPHA-1,3GAL EPITOPES; REGIMEN; MOUSE AB Nonmyeloablative induction of mixed hematopoietic chimerism provides a strategy for inducing T cell tolerance across allogeneic and xenogeneic barriers. We have utilized alpha1-3Gal transferase (GalT) knockout mice, which, like humans, produce anti-Gal natural antibodies, to investigate the ability of mixed chimerism to tolerize B cells producing antibodies of this important specificity, which limits xenotransplantation by causing hyperacute and delayed xenograft rejection. Mixed allogeneic or xenogeneic chimerism indeed tolerizes both preexisting anti-Gal-producing B cells and those developing de novo after establishment of mixed chimerism, even in presensitized mice. We present evidence that different mechanisms are involved in the tolerization of the preexisting and newly-developing antibody-secreting cells. C1 Harvard Univ, Sch Med, BMT Sect,Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, BMT Sect,Transplantat Biol Res Ctr, Massachusetts Gen Hosp, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [P01HL18646] NR 10 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2005 VL 79 IS 3 SU S BP S28 EP S29 DI 10.1097/01.0000153296.80385.e7 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 900KM UT WOS:000227213800010 PM 15699742 ER PT J AU Deng, LL Humphries, DE Arbeit, RD Carlton, LE Smole, SC Carroll, JD AF Deng, LL Humphries, DE Arbeit, RD Carlton, LE Smole, SC Carroll, JD TI Identification of a novel peptidoglycan hydrolase Cw1M in Mycobacterium tuberculosis SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE mycobacterium tuberculosis; AIDS; cell wall; cell wall hydrolase; autolysin; N-acetylmuramoyl-L-alanine amidase; N-acetylmuramic acid ID COMPLETE GENOME SEQUENCE; ENTEROCOCCUS-HIRAE ATCC-9790; BACTERIAL-CELL WALL; L-ALANINE AMIDASES; ESCHERICHIA-COLI; MAJOR AUTOLYSIN; LISTERIA-MONOCYTOGENES; NUCLEOTIDE-SEQUENCE; BACILLUS-SUBTILIS; GENE AB Mycobacterium tuberculosis is a major global pathogen whose threat has increased with the emergence of multidrug-resistant strains. The cell wall of M tuberculosis is thick, rigid, and hydrophobic, which serves to protect the organism from the environment and makes it highly impermeable to conventional antimicrobial agents. There is little known about cell wall autolysins (also referred to as peptidoglycan hydrolases) of mycobacteria. We identified an open reading frame (Rv3915) in the M tuberculosis genome designated cwlM that appeared consistent with a peptidoglycan hydrolase. The 1218-bp gene was amplified by PCR, cloned and expressed in E coli strain HMS174(DE-3), and its gene product, a 47-kDa recombinant protein, was purified and partially characterized. Purified CwlM was able to lyse whole mycobacteria, release peptidoglycan from the cell wall of Micrococcus luteus and Mycobacterium smegmatis, and cleave N-acetylmuramoyl-alanyl-D-isoglutamine, releasing free N-acetylmuramic acid. These results indicate that CwlM is a novel autolysin and identify cwlM as the first, to our knowledge, antolysin gene identified and cloned from M tuberculosis. CwlM offers a new target for a unique class of drugs that could alter the permeability of the mycobacterial cell wall and enhance the effectiveness of treatments for tuberculosis. (C) 2004 Elsevier B.V. All rights reserved. C1 Boston Univ, Sch Med, Res Serv, Dept Med,VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Deng, LL (reprint author), Boston Univ, Sch Med, Res Serv, Dept Med,VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM lynndeng@bu.edu FU NIAID NIH HHS [AI-45617] NR 41 TC 17 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD FEB 14 PY 2005 VL 1747 IS 1 BP 57 EP 66 DI 10.1016/j.bbapap.2004.09.021 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 897KP UT WOS:000227003100005 PM 15680239 ER PT J AU Weiss, RD Griffin, ML Gallop, RJ Najavits, LM Frank, A Crits-Christoph, P Thase, ME Blaine, J Gastfriend, DR Daley, D Luborsky, L AF Weiss, RD Griffin, ML Gallop, RJ Najavits, LM Frank, A Crits-Christoph, P Thase, ME Blaine, J Gastfriend, DR Daley, D Luborsky, L TI The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 16-21, 2001 CL SCOTTSDALE, AZ SP Coll Problems Drug Dependence DE cocaine; treatment; Alcoholics Anonymous; self-help; addiction; substance abuse ID SUBSTANCE-ABUSE TREATMENT; OUTPATIENT TREATMENT; INVOLVEMENT; PSYCHOTHERAPY; AFFILIATION; PROGRAM; CARE AB Objective: Although cocaine-dependent patients are frequently referred to 12-step self-help groups, little research has examined the benefits of 12-step group attendance in this population. Moreover, the distinction between attending meetings and actively participating in 12-step activities has not typically been examined. Method: In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, 487 cocaine-dependent outpatients were recruited at five sites for a randomized controlled trial of 24-week behavioral treatments. Study data were examined to see whether self-help attendance or active participation were related to subsequent drug use. Results: Twelve-step group attendance did not predict subsequent drug use. However, active 12-step participation in a given month predicted less cocaine use in the next month. Moreover, patients who increased their 12-step participation during the first 3 months of treatment had significantly less cocaine use and lower ASI Drug Use Composite scores in the subsequent 3 months. Finally, Individual Drug Counseling, based on a 12-step model, and increasing levels of 12-step participation each offered discrete benefits. Conclusions: Results suggest that active 12-step participation by cocaine-dependent patients is more important than meeting attendance, and that a combination of Individual Drug Counseling and active 12-step participation is effective for these patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02478 USA. Univ Penn, Dept Psychiat, Ctr Psychotherapy Res, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Weiss, RD (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM rweiss@mclean.harvard.edu FU NIDA NIH HHS [K02-DA 00326, K05-DA00168, R01 DA012249, U01-DA07085, U01-DA07090, U01-DA07663, U01-DA07673, U01-DA07693, U18 DA007090]; NIMH NIH HHS [K02-MH00756, P30-MH-45178] NR 41 TC 64 Z9 66 U1 7 U2 13 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 14 PY 2005 VL 77 IS 2 BP 177 EP 184 DI 10.1016/j.drugalcdep.2004.08.012 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 898QW UT WOS:000227092300008 PM 15664719 ER PT J AU Short, SM Derrien, A Narsimhan, RP Lawler, J Ingber, DE Zetter, BR AF Short, SM Derrien, A Narsimhan, RP Lawler, J Ingber, DE Zetter, BR TI Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by beta(1) integrins SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ANGIOGENESIS IN-VIVO; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; EXTRACELLULAR-MATRIX; ALPHA(V) INTEGRINS; BETA(1) INTEGRIN; BINDING DOMAIN; TUMOR-GROWTH; ACTIVATION; ADHESION AB The anti-angiogenic effect of thrombospondin-1 has been shown to be mediated through binding of the type-1 repeat (TSR) domain to the CD36 transmembrane receptor. We now report that the TSR domain can inhibit VEGF-induced migration in human umbilical vein endothelial cells (HUVEC), cells that lack CD36. Moreover, we identified beta(1) integrins as a critical receptor in TSR-mediated inhibition of migration in HUVEC. Using pharmacological inhibitors of downstream VEGF receptor effectors, we found that phosphoinositide 3-kinase (PI3k) was essential for TSR-mediated inhibition of HUVEC migration, but that neither PLCgamma nor Akt was necessary for this response. Furthermore, beta1 integrins were critical for TSR-mediated inhibition of microvascular endothelial cells, cells that express CD36. Together, our results indicate that P, integrins mediate the anti-migratory effects of TSR through a PI3k-dependent mechanism. C1 Harvard Univ, Sch Med, Vasc Biol Program, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Zetter, BR (reprint author), Harvard Univ, Sch Med, Vasc Biol Program, Childrens Hosp, Boston, MA 02115 USA. EM bruce.zetter@childrens.harvard.edu FU NCI NIH HHS [CA37393, CA45548, P01 CA045548, R01 CA037393, R37 CA037393]; NHLBI NIH HHS [HL68003, R01 HL068003] NR 67 TC 77 Z9 86 U1 0 U2 10 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 FEB 14 PY 2005 VL 168 IS 4 BP 643 EP 653 DI 10.1083/jcb.200407060 PG 11 WC Cell Biology SC Cell Biology GA 898UG UT WOS:000227101100030 PM 15716381 ER PT J AU Lechner, A Nolan, AL Blacken, RA Habener, JF AF Lechner, A Nolan, AL Blacken, RA Habener, JF TI Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE pancreas; stem cell; nestin; cytokeratin; beta-cell ID EMBRYONIC STEM-CELLS; PROGENITOR CELLS; MOUSE PANCREAS; DIFFERENTIATION; ENDOCRINE; EXPRESSION; NESTIN; TRANSPLANTATION; PROLIFERATION; NEUROGENIN3 AB Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Therefore. we investigated whether insulin-secreting cells could be differentiated in vitro from a monolayer of cells expanded from human donor pancreatic islets. We describe a three-step culture protocol that allows for the efficient generation of insulin-producing cell clusters from in vitro expanded, hormone-negative cells. These clusters express insulin at levels of up to 34% that of average freshly isolated human islets and secrete C-peptide upon membrane depolarization. They also contain cells expressing the other major islet hormones (glucagon, somatostatin, and pancreatic polypeptide). The source of the newly differentiated endocrine cells could either be indigenous stem/progenitor cells or the proliferation-associated dedifferentiation and subsequent redifferentiation of mature endocrine cells. The in vitro generated cell clusters may be efficacious in providing islet-like tissue for transplantation into diabetic recipients. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab,Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Munich, Klinikum Grosshadern, Med Klin 2, D-8000 Munich, Germany. RP Habener, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab,Howard Hughes Med Inst, Boston, MA 02115 USA. EM jhabener@partners.org FU NIDDK NIH HHS [R01 DK55365, P30 DK57521, R01 DK30834] NR 27 TC 76 Z9 87 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 11 PY 2005 VL 327 IS 2 BP 581 EP 588 DI 10.1016/j.bbrc.2004.12.043 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 888HE UT WOS:000226364000028 PM 15629153 ER PT J AU Jiang, XF AF Jiang, XF TI Random mutagenesis of the B ' A ' core domain of yeast DNA topoisomerase II and large-scale screens of mutants resistant to the anticancer drug etoposide SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE DNA topoisomerase II; etoposide; drug resistance; random mutagenesis ID ESCHERICHIA-COLI; ANTITUMOR AGENT; MECHANISM; BINDING; ALPHA; GYRASE; HYPERSENSITIVITY; SENSITIVITY; INHIBITION; AMSACRINE AB Mutagenic PCR method was applied to introduce point Mutations to the B'A' core domain of yeast DNA toposomerase II. Screens for mutants resistant to the anticancer drug etoposide were carried out in a yeast is system in the presence of high concentrations of the drug or in a drug-hypersensitive genetic background. 129 mutants were obtained from a total of 47,000 transformants. Nucleotide sequencing of 40 selected mutants showed that a large number of the mutations map to regions encoding the linker that joins the ATPase domain to the B' module and the B'A' linker. Significant reduction in catalytic activity was evident for a large fraction of mutant enzymes and all mutants were also resistant to amsacrine, another topoisomerase II drug with a different chemical structure, suggesting that few of the initiations reflect simple changes of specific amino acid side chains that are directly involved in enzyme-drug interactions. (C) 2004 Published by Elsevier Inc. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Jiang, XF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM xjiang@lroc.harvard.edu FU NIGMS NIH HHS [GM24544] NR 24 TC 3 Z9 4 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 11 PY 2005 VL 327 IS 2 BP 597 EP 603 DI 10.1016/j.bbrc.2004.12.049 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 888HE UT WOS:000226364000030 PM 15629155 ER PT J AU Noy, A Scadden, DT Lee, J Dezube, BJ Aboulafia, D Tulpule, A Walmsley, S Gill, P AF Noy, A Scadden, DT Lee, J Dezube, BJ Aboulafia, D Tulpule, A Walmsley, S Gill, P TI Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: From the AIDS malignancy consortium and IM862 study team SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignancies in AIDS and Other Immuneodeficiencies CY APR 22-24, 2002 CL Bethesda, MD ID CLINICAL-TRIALS; PROTEASE INHIBITORS; IN-VIVO; HERPESVIRUS; LYMPHOMA; CELLS AB Purpose IM862 is a synthetic dipeptide (L-glutamine L-tryptophan) with in vitro and in vivo antiangiogenic properties. Phase I/II studies showed minimal toxicity and a response rate of 36% in AIDS-Kaposi's sarcoma. We report a 24-week, randomized, double-blinded, placebo-controlled phase III trial with the phase II dose, 5 mg intranasally every other day. Patients and Methods Two hundred two HIV-positive patients were enrolled, 104 on IM862 and 98 on placebo. Results Baseline characteristics were comparable except current antiretroviral therapy: 88% versus 96% (IM862 v placebo group; P =.042). The median treatment durations were 19.5 versus 24 weeks (IM862 v placebo). No significant difference was detected in response rate (IM862, 23%; 95% Cl, 15% to 32% v placebo, 21%; 95% Cl, 14% to 31%; P =.46), time to response (8.5 weeks v 14 weeks; P =.024), or duration of response. However, IM862 was associated with both a shorter time to response (8.5 weeks v 14 weeks; P =.024) and shorter median time to progression (16 weeks, 95% Cl, 13 to 27 weeks v 35 weeks, 95% Cl, 26 to 114 weeks; P =.012). Conclusion Despite promising phase I and phase 11 studies, IM862 5 mg every other day was not superior to placebo and may accelerate time to progression. Highly active antiretroviral therapy alone was associated with a substantial rate of sustained tumor response and may have contributed to prior estimates of IM862 response. Therapeutic trials for AIDS-Kaposi's sarcoma must account for ongoing immune reconstitution in the setting of concurrent highly active antiretroviral therapy that may confound estimates of therapeutic activity. (C) 2005 by American Society of Clinical Oncology. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. USC, Keck Sch Med, Norris Canc Inst, Los Angeles, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Birmingham, AMC Operat & Stat Ctr, Birmingham, AL USA. Univ Washington, Virginia Mason Clin, Seattle, WA USA. Univ Toronto, Toronto Hosp, Toronto, ON, Canada. RP Noy, A (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM noya@mskcc.org OI Noy, Ariela/0000-0002-3001-4898 FU NCI NIH HHS [U01CA70062, U01CA070081, U01CA071375, U01CA070054, U01CA083038, U01CA070072, U01CA070068, U01CA070075, U01CA070079, U01CA83035, U01CA070047, U01CA070080, U01CA083118, U01CA070019] NR 35 TC 27 Z9 30 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2005 VL 23 IS 5 BP 990 EP 998 DI 10.1200/JCO.2005.11.043 PG 9 WC Oncology SC Oncology GA 896ZC UT WOS:000226972300007 PM 15598977 ER PT J AU Paltiel, AD Weinstein, MC Kimmel, AD Seage, GR Losina, E Zhang, H Freedberg, KA Walensky, RP AF Paltiel, AD Weinstein, MC Kimmel, AD Seage, GR Losina, E Zhang, H Freedberg, KA Walensky, RP TI Expanded screening for HIV in the United States - An analysis of cost-effectiveness SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLUS INDINAVIR; CELL COUNTS; INFECTION; COMMUNITY; SETTINGS; THERAPY; DISEASE; VACCINE; TRIALS AB BACKGROUND: Although the Centers for Disease Control and Prevention (CDC) recommend routine HIV counseling, testing, and referral (HIVCTR) in settings with at least a 1 percent prevalence of HIV, roughly 280,000 Americans are unaware of their human immunodeficiency virus (HIV) infection. The effect of expanded screening for HIV is unknown in the era of effective antiretroviral therapy. METHODS: We developed a computer simulation model of HIV screening and treatment to compare routine, voluntary HIVCTR with current practice in three target populations: ``high-risk'' (3.0 percent prevalence of undiagnosed HIV infection; 1.2 percent annual incidence); ``CDC threshold'' (1.0 percent and 0.12 percent, respectively); and ``U.S. general'' (0.1 percent and 0.01 percent). Input data were derived from clinical trials and observational cohorts. Outcomes included quality-adjusted survival, cost, and cost-effectiveness. RESULTS: In the high-risk population, the addition of one-time screening for HIV antibodies with an enzyme-linked immunosorbent assay (ELISA) to current practice was associated with earlier diagnosis of HIV (mean CD4 cell count at diagnosis, 210 vs. 154 per cubic millimeter). One-time screening also improved average survival time among HIV-infected patients (quality-adjusted survival, 220.7 months vs. 219.8 months). The incremental cost-effectiveness was $36,000 per quality-adjusted life-year gained. Testing every five years cost $50,000 per quality-adjusted life-year gained, and testing every three years cost $63,000 per quality-adjusted life-year gained. In the CDC threshold population, the cost-effectiveness ratio for one-time screening with ELISA was $38,000 per quality-adjusted life-year gained, whereas testing every five years cost $71,000 per quality-adjusted life-year gained, and testing every three years cost $85,000 per quality-adjusted life-year gained. In the U.S. general population, one-time screening cost $113,000 per quality-adjusted life-year gained. CONCLUSIONS: In all but the lowest-risk populations, routine, voluntary screening for HIV once every three to five years is justified on both clinical and cost-effectiveness grounds. One-time screening in the general population may also be cost-effective. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. RP Paltiel, AD (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM david.paltiel@yale.edu FU NIAID NIH HHS [K23AI01794, K23 AI001794, K24 AI062476, K24AI062476, K25 AI050436, K25AI50436, P30 AI042851, P30AI42851, R01 AI042006, R01AI42006]; NIDA NIH HHS [R01 DA015612, R01DA015612]; NIMH NIH HHS [R01 MH065869]; PHS HHS [S1396-20/21] NR 36 TC 342 Z9 350 U1 2 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 10 PY 2005 VL 352 IS 6 BP 586 EP 595 DI 10.1056/NEJMsa042088 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 895KY UT WOS:000226862100008 PM 15703423 ER PT J AU Weller, PF Durand, ML Pilch, BZ Harris, NL Kazda, G Ryan, ET Hooper, D AF Weller, PF Durand, ML Pilch, BZ Harris, NL Kazda, G Ryan, ET Hooper, D TI Case 4-2005: A 35-year-old man with nasal congestion, swelling, and pain - Mucocutaneous leishmaniasis due to infection by Leishmania viannia braziliensis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MUCOSAL LEISHMANIASIS; ESPUNDIA C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Allerg & Inflammat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weller, PF (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. NR 20 TC 9 Z9 9 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 FEB 10 PY 2005 VL 352 IS 6 BP 609 EP 615 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 895KY UT WOS:000226862100012 PM 15703426 ER PT J AU Iwata, S Souta-Kuribara, A Yamakawa, A Sasaki, T Shimizu, T Hosono, O Kawasaki, H Tanaka, H Dang, NH Watanabe, T Arima, N Morimoto, C AF Iwata, S Souta-Kuribara, A Yamakawa, A Sasaki, T Shimizu, T Hosono, O Kawasaki, H Tanaka, H Dang, NH Watanabe, T Arima, N Morimoto, C TI HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L) SO ONCOGENE LA English DT Article DE ATL; Tax; HTLV-I; NF-kappa B; Cas-L; HEF1 ID T-CELL LEUKEMIA; VIRUS TYPE-I; MEDIATED TYROSINE PHOSPHORYLATION; FOCAL ADHESION KINASE; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; GENE-EXPRESSION; PROTEIN; ACTIVATION; TRANSACTIVATION AB Crk-associated substrate lymphocyte type (Cas-L) is a docking protein that is heavily tyrosine phosphorylated by the engagement of beta1 integrins in T cells. In the present study, we attempted to evaluate the role of Cas-L in the pathophysiology of adult T-cell leukemia (ATL). Examination of peripheral blood mononuclear cells from ATL patients as well as ATL-derived T cell lines showed an elevation of Cas-L in these cells. We showed that tyrosine phosphorylation as well as expression of Cas-L was markedly elevated through the induction of human T-lymphotropic virus type I ( HTLV-I) Tax in JPX-9 cells, with these cells showing marked motile behavior on the ligands for integrins. We next performed yeast two-hybrid screening of cDNA library from an HTLV-I-transformed T cell line, which resulted in the identification of Tax as a putative binding partner for Cas-L. Co-precipitation experiments revealed that the serine-rich region of Cas-L might serve as the binding site with the highest afinity for Tax. Co-localization study showed that Tax and Cas-L partly merged in the cytoplasm. Finally, we showed that exogenous Cas-L inhibited Tax-mediated transactivation of nuclear factor kappaB ( NF-kappaB), while Tax-independent activation of NF-kappaB remained intact, hence indicating that Cas-L might specically regulate Tax-NF-kappaB pathway. C1 Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Clin Immunol,Minato Ku, Tokyo 1088639, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Keio Univ, Sch Med, Dept Internal Med, Shinjyuku Ku, Tokyo 1608582, Japan. Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Lab Tumor Cell Biol,Minato Ku, Tokyo 1088639, Japan. Kagoshima Univ, Fac Med, Ctr Chron Viral Dis, Div Host Response, Kagoshima 8908520, Japan. RP Morimoto, C (reprint author), Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Clin Immunol,Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. EM morimoto@ims.u-tokyo.ac.jp RI Iwata, Satoshi/A-8819-2011 NR 47 TC 17 Z9 18 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 FEB 10 PY 2005 VL 24 IS 7 BP 1262 EP 1271 DI 10.1038/sj.onc.1208261 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 895XV UT WOS:000226898700013 PM 15592516 ER PT J AU Las, L Stern, EA Nelken, I AF Las, L Stern, EA Nelken, I TI Representation of tone in fluctuating maskers in the ascending auditory system SO JOURNAL OF NEUROSCIENCE LA English DT Article DE auditory cortex; auditory thalamus; inferior colliculus; physiology; cat; comodulation masking release ID COMODULATION MASKING RELEASE; NEURONS IN-VIVO; AMPLITUDE-MODULATED MASKERS; VISUAL CORTICAL-NEURONS; DIRECTION SELECTIVITY; SHUNTING INHIBITION; RECEPTIVE-FIELDS; COCHLEAR NUCLEUS; SIGNAL-DETECTION; NEURAL MODEL AB Humans and animals detect low-level tones masked by slowly fluctuating noise very efficiently. A possible neuronal correlate of this phenomenon is the ability of low-level tones to suppress neuronal locking to the envelope of the fluctuating noise ("locking suppression"). Using in vivo intracellular and extracellular recordings in cats, we studied neuronal responses to combinations of fluctuating noise and tones in three successive auditory stations: inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1). We found that although the most sensitive responses in the IC were approximately isomorphic to the physical structure of the sounds, with only a small perturbation in the responses to the fluctuating noise after the addition of low-level tones, some neurons in the MGB and all A1 neurons displayed striking suppressive effects. These neurons were hypersensitive, showing suppression already with tone levels lower than the threshold of the neurons in silence. The hypersensitive locking suppression in A1 and MGB had a special timing structure, starting >75 ms after tone onset. Our findings show a qualitative change in the representation of tone in fluctuating noise along the IC-MGB-A1 axis, suggesting the gradual segregation of signal from noise and the representation of the signal as a separate perceptual object in A1. C1 Hebrew Univ Jerusalem, Dept Neurobiol, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Interdisciplinary Ctr Neural Computat, IL-91904 Jerusalem, Israel. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. RP Nelken, I (reprint author), Hebrew Univ Jerusalem, Dept Neurobiol, Edmund Safra Campus,Givat Ram, IL-91904 Jerusalem, Israel. EM israel@md.huji.ac.il RI Nelken, Israel/B-7753-2011 OI Nelken, Israel/0000-0002-6645-107X NR 46 TC 54 Z9 54 U1 1 U2 8 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 FEB 9 PY 2005 VL 25 IS 6 BP 1503 EP 1513 DI 10.1523/JNEUROSCI.4007-04.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 895XP UT WOS:000226898100020 PM 15703404 ER EF