FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cooper, GF Abraham, V Aliferis, CF Aronis, JM Buchanan, BG Caruana, R Fine, MJ Janosky, JE Livingston, G Mitchell, T Monti, S Spirtes, P AF Cooper, GF Abraham, V Aliferis, CF Aronis, JM Buchanan, BG Caruana, R Fine, MJ Janosky, JE Livingston, G Mitchell, T Monti, S Spirtes, P TI Predicting dire outcomes of patients with community acquired pneumonia SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE machine learning; community acquired pneumonia; outcome prediction; quality and cost of healthcare delivery ID LIKELIHOOD; SELECTION; COST AB Comm unity-acquired pneumonia (CAP) is an important clinical condition with regard to patient mortality, patient morbidity, and healthcare resource utilization. The assessment of the likely clinical course of a CAP patient can significantly influence decision making about whether to treat the patient as an inpatient or as an outpatient. That decision can in turn influence resource utilization, as well as patient well being. Predicting dire outcomes, such as mortality or severe clinical complications, is a particularly important component in assessing the clinical course of patients. We used a training set of 1601 CAP patient cases to construct 11 statistical and machine-learning models that predict dire outcomes. We evaluated the resulting models on 686 additional CAP-patient cases. The primary goal was not to compare these learning algorithms as a study end point; rather, it was to develop the best model possible to predict dire outcomes. A special version of an artificial neural network (NN) model predicted dire outcomes the best. Using the 686 test cases, we estimated the expected healthcare quality and cost impact of applying the NN model in practice. The particular, quantitative results of this analysis are based on a number of assumptions that we make explicit; they will require further study and validation. Nonetheless, the general implication of the analysis seems robust, namely, that even small improvements in predictive performance for prevalent and costly diseases, such as CAP, are likely to result in significant improvements in the quality and efficiency of healthcare delivery. Therefore, seeking models with the highest possible level of predictive performance is important. Consequently, seeking ever better machine-learning and statistical modeling methods is of great practical significance. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Ctr Biomed Informat, Pittsburgh, PA 15213 USA. Stanford Univ, Meyler Lib 260, Stanford, CA 94305 USA. Vanderbilt Univ, Dept Biomed Informat, Eskind Lib 412, Nashville, TN 37232 USA. Univ Pittsburgh, Dept Comp Sci, Pittsburgh, PA 15260 USA. Cornell Univ, Dept Comp Sci, Ithaca, NY 14853 USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Family Med & Clin Epidemiol, Pittsburgh, PA 15261 USA. Univ Massachusetts, Dept Comp Sci, Lowell, MA 01854 USA. Carnegie Mellon Univ, Ctr Automated Learning & Discovery, Pittsburgh, PA 15213 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Carnegie Mellon Univ, Dept Philosophy, Pittsburgh, PA 15213 USA. RP Cooper, GF (reprint author), Univ Pittsburgh, Ctr Biomed Informat, Suite 8084 Forber Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. EM gfc@cbmi.pitt.edu OI Monti, Stefano/0000-0002-9376-0660 NR 34 TC 10 Z9 10 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD OCT PY 2005 VL 38 IS 5 BP 347 EP 366 DI 10.1016/j.jbi.2005.02.005 PG 20 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 976MV UT WOS:000232738600002 PM 16198995 ER PT J AU Carson, P Massie, BM McKelvie, R McMurray, J Komajda, M Zile, M Ptaszynska, A Frangin, G AF Carson, P Massie, BM McKelvie, R McMurray, J Komajda, M Zile, M Ptaszynska, A Frangin, G CA I-PRESERVE Investigators TI The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial: Rationale and design SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE AT(1)-receptor blockers; ACE inhibition; left ventricular function; congestive heart failure ID VENTRICULAR EJECTION FRACTION; ANGIOTENSIN-CONVERTING ENZYME; CLINICAL CHARACTERISTICS; DIAGNOSIS; HYPERTROPHY; DYSFUNCTION; RELAXATION; PROGNOSIS; MORTALITY; OUTCOMES AB Background: Although 40% to 50% of patients with chronic heart failure (HE) have relatively preserved systolic function (PSF), few trials have been conducted in this population and treatment guidelines do not include evidence-based recommendations. Methods and Results: The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) is enrolling 4100 subjects with HF-PSF to evaluate whether 300 mg irbesartan is superior to placebo in reducing mortality and prespecified categories of cardiovascular hospitalizations. The principal inclusion criteria are age >= 60 years, heart failure symptoms, an ejection fraction >= 45%, and either hospitalization for heart failure within 6 months or corroborative evidence of heart failure or the substrate for diastolic heart failure. Additional secondary end points include cardiovascular mortality, cattle-specific mortality and morbidity, change in New York Heart Association functional class, quality of life, and N-terminal pro-BNP measurements. Follow-up will continue until 1440 patients experience a primary end point. Substudies will evaluate changes in echocardiographic measurements and serum collagen markers. Conclusion: I-PRESERVE is the largest trial in this understudied area and will provide crucial information on the characteristics and course of the syndrome, as well as the efficacy of the angiotensin receptor blocker irbesartan. C1 Georgetown Univ Hosp, Dept Vet Affairs Med Ctr, Washington, DC 20007 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VAMC, San Francisco, CA USA. McMaster Univ, Hamilton Hlth Sci, Hamilton, ON, Canada. Univ Glasgow, CRI Heart Failure, Glasgow G12 8QQ, Lanark, Scotland. Hop La Pitie Salpetriere, Dept Cardiol, Paris, France. Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. Bristol Myers Squibb Co, Div Cardiol, Princeton, NJ USA. Sanofi Synthelabo Rech, Montpellier, France. RP Carson, P (reprint author), MICU, 50 Irving St, Washington, DC 20420 USA. RI Casademont, Jordi/A-6828-2010 OI mcmurray, john/0000-0002-6317-3975; Casademont, Jordi/0000-0002-8100-1827 NR 24 TC 77 Z9 81 U1 1 U2 1 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 OCT PY 2005 VL 11 IS 8 BP 576 EP 585 DI 10.1016/j.cardfail.2005.06.432 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 981MR UT WOS:000233093200002 PM 16230259 ER PT J AU London, MJ Henderson, WG AF London, MJ Henderson, WG TI Perioperative pharmacologic cardioprotection and sodium hydrogen ion exchange inhibitors: One step forward and two steps back? SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Editorial Material C1 Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Natl Surg Qual Improvement Program, Aurora, CO USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Dept Prevent Med & Biometr, Aurora, CO USA. RP London, MJ (reprint author), Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. NR 62 TC 0 Z9 0 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2005 VL 19 IS 5 BP 565 EP 569 DI 10.1053/j.jvca.2005.07.027 PG 5 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 980YP UT WOS:000233054400001 PM 16202887 ER PT J AU Albrecht, MA Streckenbach, SC Alston, TA AF Albrecht, MA Streckenbach, SC Alston, TA TI Intra-annular leak of a pericardial prosthetic valve SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE doppler echocardiography; pericardial prosthetic valve C1 Harvard Univ, Dept Anesthesia & Crit Care, Cardiac Anesthesia Grp, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Cardiac Anesthesia Grp, Massachusetts Gen Hosp,Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM talston@partners.org NR 2 TC 0 Z9 0 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2005 VL 19 IS 5 BP 691 EP 692 DI 10.1053/j.jvca.2005.05.015 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 980YP UT WOS:000233054400026 PM 16202912 ER PT J AU Tofovic, SP Salah, EM Mady, HH Jackson, EK Melhem, ME AF Tofovic, SP Salah, EM Mady, HH Jackson, EK Melhem, ME TI Estradiol metabolites attenuate monocrotaline-induced pulmonary hypertension in rats SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE 17 beta estradiol; metabolites; pulmonary arterial hypertension ID VASCULAR ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; PHYSIOLOGICAL CONCENTRATIONS; ESTROGEN METABOLITE; CHRONIC HYPOXIA; 2-METHOXYESTRADIOL; PROLIFERATION; APOPTOSIS; 2-HYDROXYESTRADIOL; EXPRESSION AB Pulmonary arterial hypertension (PH) is a deadly disease characterized by pulmonary arterial vasoconstriction and hypertension, pulmonary vasculature remodeling, and right ventricular hypertrophy. Our previous in vivo studies, performed in several models of cardiac, vascular, and/or renal injury, suggest that the metabolites of 17 beta-estradiol may inhibit vascular and cardiac remodeling. The goal of this study was to determine whether 2-methoxyestradiol (2ME), major non-estrogenic estradiol metabolite, prevents the development and/or retards the progression of monocrotaline (MCT)-induced PH. First, a total of 27 male Sprague Dawley rats were injected with distillated water (Cont, n = 6) or monocrotaline (MCT; 60 mg/kg, i.p.; n = 21). Subsets of MCT animals (n = 7 per group) received 2ME or its metabolic precursor 2-hydroxyestradiol (2HE; 10 mu g/kg/h via osmotic minipumps) for 21 days. Next, an additional set (n = 24) of control and MCT rats was monitored for 28 days, before right ventricular peak systolic pressure (RVPSP) was measured. Some pulmonary hypertensive animals (n = 8) were treated with 2ME (10 mu g/kg/h) beginning from day 14 after MCT administration. MCT caused pulmonary hypertension (ie, increased right ventricle/left ventricle + septum [RV/LV+S] ratio and wall thickness of small-sized pulmonary arteries, and elevated RVPSP) and produced high and late (days 22 to 27) mortality. Pulmonary hypertension was associated with strong proliferative response (PCNA staining) and marked inflammation (ED1 + cells) in lungs. Both metabolites significantly attenuated the RV/LV+S ratio and pulmonary arteries media hypertrophy and reduced proliferative and inflammatory responses in the lungs. Furthermore, in diseased animals, 2ME (given from day 14 to 28) significantly decreased RVPSP, RV/LV+S ratio and wall thickness, and reduced mortality by 80% (mortality rate: 62.5% vs. 12.5%, MCT vs. MCT+2ME day 14 to 28). This study provides the first evidence that 2ME, a major non-estrogenic, non-carcinogenic metabolite of estradiol, prevents the development and retards the progression of monocrotaline-induced pulmonary hypertension. Further evaluation of 2ME for management of pulmonary arterial hypertension is warranted. C1 Univ Pittsburgh, Sch Med, Ctr Clin Pharmacol, Pittsburgh, PA 15219 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pathol, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pharmacol, Sch Med, Pittsburgh, PA USA. RP Tofovic, SP (reprint author), Univ Pittsburgh, Sch Med, Ctr Clin Pharmacol, 100 Technol Dr,Suite 450, Pittsburgh, PA 15219 USA. EM tofovic@dom.pitt.edu NR 49 TC 35 Z9 35 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD OCT PY 2005 VL 46 IS 4 BP 430 EP 437 DI 10.1097/01.fjc.0000175878.32920.17 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 009EL UT WOS:000235094000005 PM 16160593 ER PT J AU Taneri, S Koch, JM Melki, SA Azar, DT AF Taneri, S Koch, JM Melki, SA Azar, DT TI Mitomycin-C assisted photorefractive keratectomy in the treatment of buttonholed laser in situ keratomileusis flaps associated with epithelial ingrowth SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT 21st Congress of the European-Society-of-Cataract-and-Refractive-Surgeons CY SEP, 2003 CL Munich, GERMANY SP European Soc Cataract & Refract Surg ID PROPHYLACTIC USE; SUBEPITHELIAL FIBROSIS; HAZE FORMATION; LASIK FLAP; MANAGEMENT; COMPLICATIONS; ACCURACY; PACHYMETRY; MYOPIA; PRK AB The prophylactic intraoperative use of mitomycin-C (MMC) to prevent haze and scarring after excimer laser surface ablation (phototherapeutic/photorefractive keratectomy [PTK/PRK]) in an eye with a previous laser in situ keratomileusis (LASIK) flap buttonhole with epithelial ingrowth is described. A well-centered buttonhole measuring 2.0 mm in diameter was cut within a thin LASIK flap in an amblyopic eye. Over the next 8 weeks, corneal haze and progressive epithelial ingrowth formed centrally. An early transepithelial PTK/PRK approach was chosen to manage the buttonhole together with the epithelial ingrowth and to treat ametropia before the onset of scarring. The approach included epithelial removal with PTK, application of MMC 0.02% for 1 minute, irrigation, a short waiting period to allow for diffusion, PRK correction of -4.0 diopters without nomogram adjustment, and bandage contact lens. A regimen of prednisolone acetate 1% and ofloxacin 0.03% 5 times a day for 1 week (steroid tapered) was prescribed. Epithelial ingrowth was removed successfully. Minimal haze formation was visible 2 weeks after the retreatment but did not reduce best spectacle-corrected visual acuity (BSCVA) and resolved within the next few weeks. After 6 weeks, uncorrected visual acuity was equal to BSCVA preoperatively (20/50). There was no evidence of recurrent epithelial ingrowth or central scarring after 24 months. Transepithelial PTK/PRK was effective in managing central epithelial ingrowth in a buttonholed LASIK flap. Prophylactic intraoperative use of MMC may reduce haze formation and corneal scarring in early treatments and may also prevent recurrent epithelial ingrowth. This approach may offer faster visual recovery and no risk for a repeated buttonhole creation compared with the widespread recutting a new flap after a couple of months. The optimal application time and concentration of MMC need to be established. C1 Zentrum Refrakt Chirurg Munster, D-48145 Munster, Germany. Boston Eye Grp, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Taneri, S (reprint author), Zentrum Refrakt Chirurg Munster, Hohenzollernring 57, D-48145 Munster, Germany. EM taneri@refraktives-zentrum.de OI Taneri, Suphi/0000-0003-0593-6847 NR 25 TC 24 Z9 24 U1 0 U2 2 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 OCT PY 2005 VL 31 IS 10 BP 2026 EP 2030 DI 10.1016/j.jcrs.2005.06.035 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 996PK UT WOS:000234186300043 PM 16338580 ER PT J AU Wilens, TE AF Wilens, TE TI The need to study substance use disorders SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2005 VL 15 IS 5 BP 720 EP 722 DI 10.1089/cap.2005.15.720 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 982EB UT WOS:000233139600002 PM 16262588 ER PT J AU Gignac, M Wilens, TE Biederman, J Kwon, A Mick, E Swezey, A AF Gignac, M Wilens, TE Biederman, J Kwon, A Mick, E Swezey, A TI Assessing cannabis use in adolescents and young adults: What do urine screen and parental report tell you? SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT HYPERACTIVITY; SUBSTANCE USE DISORDERS; DRUG-USE; SELF-REPORT; ADHD; PREDICTORS; RATIONALE; PATTERNS; OUTCOMES; CHILDREN AB Objectives: Our analysis compares three approaches to detect the most common drug abused in early adulthood, cannabis: (1) report on direct structured interview; (2) indirect parental report; and (3) urine toxicology screen. Methods: We examined data on 207 subjects (36% also met criteria for alcohol abuse; 9% for alcohol dependence) derived from two prospective and ongoing family studies of boys and girls with or without attention-deficit/hyperactivity disorder (ADHD). Assessments relied on the Schedule for Affective Disorders and Schizophrenia (K-SADS-E; under 18 years of age) and on the Structured Clinical Interview for DSM-IV (SCID-IV; over 18 years of age). Urine samples were analyzed with Auccusign DOA5 (on-site screening assay). Results: Ninety-seven percent (97%) of individuals, who reported no use of cannabis within the past month, had a negative urine screening and 79% of individuals, who endorsed cannabis abuse/dependence, had a positive urine screening. The sensitivity of the direct structured interview report was 91%, the specificity 87%, the positive predicting value 67%, and the negative predictive value 97%. Indirect parental reports were found to be less informative on cannabis use than direct report. Conclusion: Direct report of cannabis use, abuse, or dependence during the structured interview is both sensitive and specific when compared to urine toxicology screens and indirect parental reports. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gignac, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM mgignac@partners.org OI Mick, Eric/0000-0001-8505-8145 FU NIDA NIH HHS [DA11929-01A2, DA14419-01] NR 28 TC 22 Z9 22 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2005 VL 15 IS 5 BP 742 EP 750 DI 10.1089/cap.2005.15.742 PG 9 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 982EB UT WOS:000233139600005 PM 16262591 ER PT J AU Solhkhah, R Wilens, TE Daly, J Prince, JB Van Patten, SL Biederman, J AF Solhkhah, R Wilens, TE Daly, J Prince, JB Van Patten, SL Biederman, J TI Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention/deficit/hyperactivity disorder and mood disorders SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT 22-28, 2001 CL HONOLULU, HI SP Amer Acad Child & Adolescent Psychiat ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DRUG-USE; PSYCHIATRIC COMORBIDITY; SUSTAINED-RELEASE; DEFICIT DISORDER; MENTAL-HEALTH; OPEN TRIAL; DEPRESSION; ALCOHOL; METHYLPHENIDATE AB Objective: Few studies exist on pharmacological interventions for adolescents with substance use disorders (SUD). To this end, we evaluated the response of bupropion hydrochloride sustained release (SR) in SUD adolescents with comorbid psychopathology (both attention-deficit/hyperactivity disorder (ADHD) and a mood disorder). Methods: Fourteen adolescent outpatients were treated naturalistically and followed openly for 6 months. Adolescents were rated using the Drug Use Screening Inventory-Revised (DUSI-R), ADHD Symptom Checklist, and the Hamilton Rating Scale for Depression (HAM-D). Clinical Global Impression (CGI) Scale scores were obtained for Substance Abuse, ADHD, Anxiety, and Depression. The ratings were completed at baseline, at month 3, and at the 6-month endpoint. Bupropion SR was initiated at 100 mg once-daily and titrated naturalistically to a maximum dose of 400 mg/day. Results: Of the 14 subjects followed, 13 subjects completed 6 months of treatment. At the 6-month endpoint compared to baseline, treatment with bupropion was associated with clinical and significant reductions in DUSI scores (-39%; p < 0.05), ADHD symptom checklist (-43%; p < 0.001), HAM-D (-76%; p <= 0.001); and reductions in the CGIs for ADHD (p <= 0.001), depression (p <= 0.001), and substance abuse (p < 0.05). The mean daily dose of bupropion SR was 315 mg (in divided doses). No significant adverse events were noted during the follow-up period. Conclusions: These naturalistic data suggest that bupropion is well tolerated and may be an effective medication for the treatment of substance abusing adolescents with comorbid mood disorders and ADHD. C1 Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Solhkhah, R (reprint author), St Lukes Roosevelt Hosp, Div Child & Adolescent Psychiat, 411 W 114th St, New York, NY 10025 USA. EM rsolhkhah@chpnet.org FU NIDA NIH HHS [R29DA11315] NR 45 TC 37 Z9 38 U1 3 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2005 VL 15 IS 5 BP 777 EP 786 DI 10.1089/cap.2005.15.777 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 982EB UT WOS:000233139600008 PM 16262594 ER PT J AU Wilens, TE Monuteaux, MC Snyder, LE Moore, H Whitley, J Gignac, M AF Wilens, TE Monuteaux, MC Snyder, LE Moore, H Whitley, J Gignac, M TI The clinical dilemma of using medications in substance-abusing adolescents and adults with attention-deficit/hyperactivity disorder: What does the literature tell us? SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC COMORBIDITY; CONDUCT DISORDER; COCAINE ABUSERS; FOLLOW-UP; DEPENDENT DELINQUENTS; CONTROLLED-TRIAL; ADHD; METAANALYSIS; BUPROPION AB Objective: Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are increasingly recognized in clinical practice. The role of pharmacological treatment for ADHD in these comorbid individuals remains unclear. Methods: A systematic review of the medical literature was conducted through PubMed, supplemented with data from scientific presentations, to evaluate the role of medication treatment of ADHD in substance abusing individuals with ADHD. Meta-analysis was used to evaluate the effects of medication therapy on ADHD and SUD outcomes in general, while specifically addressing trial design, trial duration, retention, class of medication, age group, concurrent psychotherapy, and outcome in both SUD and ADHD domains. Results: Four studies in adolescents and five studies in adults with ADHD plus SUD were identified (two controlled and seven open studies; n = 222 subjects). The standard mean difference (SMD) indicated statistically significant improvements in ADHD and SUD that were not maintained when evaluating controlled studies only. Albeit limited by power, trial duration, retention rate, and age group did not influence outcome. No worsening of SUD or drug-drug interactions were observed in any of the studies. The results could not be accounted for by any single study or by publication bias. Conclusion: Treating ADHD pharmacologically in individuals with ADHD plus SUD has a moderate impact on ADHD and SUD that is not observed in controlled trials and does not result in worsening of SUD or adverse interactions specific to SUD. Further controlled trials evaluating the effect of novel combinations of psychotherapy and ADHD pharmacotherapy on SUD relapse in these groups are warranted. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Clin Res Program Pediat Psychopharmacol, YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [DA14419, K24 DA016264] NR 64 TC 18 Z9 18 U1 3 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2005 VL 15 IS 5 BP 787 EP 798 DI 10.1089/cap.2005.15.787 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 982EB UT WOS:000233139600009 PM 16262595 ER PT J AU Waxmonsky, JG Wilens, TE AF Waxmonsky, JG Wilens, TE TI Pharmacotherapy of adolescent substance use disorders: A review of the literature SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; ALCOHOL-USE DISORDERS; DEFICIT HYPERACTIVITY DISORDER; DRUG-DEPENDENT DELINQUENTS; PSYCHIATRIC COMORBIDITY; DOUBLE-BLIND; MAJOR DEPRESSION; BIPOLAR DISORDER AB Objective: Substance use disorders (SUD) are increasingly conceptualized as developing during adolescence. Moreover, adolescent SUD are viewed as one of the most difficult mental health conditions to treat. The role of pharmacotherapy for adolescents with SUD is not well delineated. We systematically reviewed existing pharmacotherapy studies of adolescent SUD. Methods: A computerized search of the literature addressing the pharmacotherapy of SUD in adolescents was performed. Data from relevant peer-reviewed scientific presentations were also included. Results: Five case reports (n = 8 subjects), six open studies that primarily addressed SUD with comorbid psychiatric disorders (n = 73 subjects), and five placebo-controlled studies (n = 156 subjects) on the pharmacological treatment of youths with SUD were identified. Pharmacological agents appear to reduce comorbid psychopathology with a milder reduction in SUD symptoms. The most robust evidence exists for the treatment of SUD comorbid with affective disorders. There is a limited database supporting the use of agents to reduce substance craving and the preventative effects of pharmacotherapy on subsequent SUD development in adolescents with specific psychiatric disorders. Conclusion: Further controlled studies directed at reducing drug use and craving, and guiding the integration of pharmacotherapy and psychosocial interventions for SUD with the treatment of comorbid psychiatric illness, are necessary. C1 SUNY Buffalo, Buffalo, NY 14260 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Waxmonsky, JG (reprint author), SUNY Buffalo, Dept Child Psychiat, Millard Fillmore Gates Hosp, 8th Floor,3 Gates Circle, Buffalo, NY 14209 USA. EM JGW@Buffalo.edu NR 118 TC 18 Z9 19 U1 8 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2005 VL 15 IS 5 BP 810 EP 825 DI 10.1089/cap.2005.15.810 PG 16 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 982EB UT WOS:000233139600011 PM 16262597 ER PT J AU Kuban, KCK O'Shea, M Allred, E Leviton, A Gilmore, H DuPlessis, A Krishnamoorthy, K Hahn, C Soul, J O'Connor, SE Miller, K Church, PT Keller, C Bream, R Adair, R Miller, A Romano, E Bassan, H Kerkering, K Engelke, S Marshall, D Milowic, K Wereszczak, J Hubbard, C Washburn, L Dillard, R Heller, C Burdo-Hartman, W Fagerman, L Sutton, D Karna, P Olomu, N Caldarelli, L Oca, M Lohr, K Scheiner, A AF Kuban, KCK O'Shea, M Allred, E Leviton, A Gilmore, H DuPlessis, A Krishnamoorthy, K Hahn, C Soul, J O'Connor, SE Miller, K Church, PT Keller, C Bream, R Adair, R Miller, A Romano, E Bassan, H Kerkering, K Engelke, S Marshall, D Milowic, K Wereszczak, J Hubbard, C Washburn, L Dillard, R Heller, C Burdo-Hartman, W Fagerman, L Sutton, D Karna, P Olomu, N Caldarelli, L Oca, M Lohr, K Scheiner, A TI Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Child-Neurology-Society CY OCT 13-16, 2004 CL Toronto, CANADA SP Child Neurol Soc ID LOW-BIRTH-WEIGHT; HYPOTHERMIC CIRCULATORY ARREST; FLOW CARDIOPULMONARY BYPASS; CEREBRAL-PALSY; PREMATURE-INFANTS; GESTATIONAL-AGE; HEART-SURGERY; FOLLOW-UP; RELIABILITY; POPULATION AB In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age I year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals. C1 Boston Univ, Med Ctr, Dept Pediat, Div Pediat Neurol, Boston, MA 02118 USA. Wake Forest Univ, Dept Neonatol, Winston Salem, NC 27109 USA. Harvard Univ, Childrens Hosp Boston, Dept Neurol, Neuroepidemiol Unit, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA. Harvard Univ, Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Tufts Univ, New England Med Ctr, Medford, MA 02155 USA. Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. Yale Univ, Med Ctr, New Haven, CT 06520 USA. E Carolina Univ, Greenville, NC 27858 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Michigan State Univ, Sparrow Med Ctr, E Lansing, MI 48824 USA. William Beaumont Hosp, Neonatol Unit, Royal Oak, MI 48072 USA. RP Kuban, KCK (reprint author), Boston Univ, Med Ctr, Dept Pediat, Div Pediat Neurol, 1 Boston Med Ctr Pl,Dowling Bldg,Room 3314, Boston, MA 02118 USA. EM Karl.Kuban@bmc.org RI Hahn, Cecil/J-3372-2016 OI Hahn, Cecil/0000-0002-0887-8761 FU NINDS NIH HHS [NS40069] NR 21 TC 37 Z9 37 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 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD OCT PY 2005 VL 20 IS 10 BP 829 EP 831 DI 10.1177/08830738050200101001 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 004BR UT WOS:000234727500010 PM 16417880 ER PT J AU Doherty, C Goh, S Poussaint, TY Erdag, N Thiele, EA AF Doherty, C Goh, S Poussaint, TY Erdag, N Thiele, EA TI Prognostic significance of tuber count and location in tuberous sclerosis complex SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID SEVERITY; AUTISM; EPILEPSY AB The objectives of this study were (1) to test the utility of tuber count and tuber location as biomarkers of disease severity in patients with tuberous sclerosis complex and (2) to examine the relationship between gene mutation, tuber count, and tuber location. We found that an increased tuber count per lobe and in total was associated with an increased risk of infantile spasms (P <. 0 1). Increased tuber count in the occipital lobe was associated with an increased risk of pervasive developmental disorder (P =.0074). The mean tuber count per lobe and in total was higher in those with poorly controlled seizures and those with off-track development; however, these differences were not statistically significant (P >.01). The TSC2 gene mutation was associated with a significant increase in the tuber count per lobe and in total (P <.0 1). In summary, increased tuber count is strongly associated with infantile spasms and a TSC2 gene mutation. Seizure control and developmental delay do not show the strong association with tuber count suggested by the earlier literature. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,VBK 830, Boston, MA 02114 USA. EM ethiele@partners.org NR 24 TC 35 Z9 36 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD OCT PY 2005 VL 20 IS 10 BP 837 EP 841 DI 10.1177/08830738050200101301 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 004BR UT WOS:000234727500013 PM 16417883 ER PT J AU van der Meulen, EM Bakker, SC Pauls, DL Oteman, N Kruitwagen, CLJJ Pearson, PL Sinke, RJ Buitelaar, JK AF van der Meulen, EM Bakker, SC Pauls, DL Oteman, N Kruitwagen, CLJJ Pearson, PL Sinke, RJ Buitelaar, JK TI High sibling correlation on methylphenidate response but no association with DAT1-10R homozygosity in Dutch sibpairs with ADHD SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE ADD; ADHD; genetics; methylphenidate; etiology; DAT1; DRD4 ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; 7-REPEAT ALLELE; CHILDREN; METAANALYSIS; LINKAGE; SAMPLE; DRD4 AB Background: A minority of patients with attention-deficit hyperactivity disorder ( ADHD) do not respond favorably to methylphenidate. This has been partially associated with homozygosity for the Dopamine transporter (DAT1) 10-repeat allele and the presence of one or two Dopamine D4 receptor (DRD4) 7-repeat alleles. This study examined the sibling correlation of methylphenidate response rate and the possible association between response rate and these risk alleles. Methods: A sample of 82 Dutch children with ADHD, from 54 families, (including 30 singletons and 28 sib pairs), who used methylphenidate, was phenotyped according to DSM-IV criteria. Patients were members of affected sib pairs and were genotyped for DAT1 and DRD4. The sibling Intraclass Correlation Coefficient for methylphenidate response rate was calculated. The association between individual response rates and the risk alleles was examined using linear regression techniques. Results: The Intraclass Correlation Coefficient was significant (r = .563, p = .001). No evidence was found establishing an association between methylphenidate response and DAT1-homozygosity. There was a positive trend towards association with the presence of one or two DRD4-7R alleles. Conclusions: The sibling correlation may indicate a familial clustering of methylphenidate response. This response is possibly associated with the presence of one or two alleles at the DRD4-7R locus, but not with DAT1-10R homozygosity in the Dutch population. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA USA. Univ Utrecht, Med Ctr, Dept Med Genet, Utrecht, Netherlands. Univ Utrecht, Ctr Biostat, Utrecht, Netherlands. Radboud Univ, Dept Psychiat, Nijmegen Med Ctr, Nijmegen, Netherlands. RP van der Meulen, EM (reprint author), Unit Psychiat & Neurodev Genet, 149 13th St,10th Floor, Charlestown, MA 02129 USA. EM Evandermeulen_2000@yahoo.com RI Sinke, Richard/A-1462-2009; Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 24 TC 29 Z9 29 U1 4 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2005 VL 46 IS 10 BP 1074 EP 1080 PG 7 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 966FQ UT WOS:000232005900008 PM 16178931 ER PT J AU Davidson, PSR Cook, SP Glisky, EL Verfaellie, M Rapcsak, SZ AF Davidson, PSR Cook, SP Glisky, EL Verfaellie, M Rapcsak, SZ TI Source memory in the real world: A neuropsychological study of flashbulb memory SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the International-Neuropsychological-Society CY FEB 05-08, 2003 CL HONOLULU, HI SP Int Neuropsychol Soc ID FRONTAL-LOBE LESIONS; OLDER-ADULTS; AMNESIC PATIENTS; TEMPORAL-LOBE; IMPAIRMENT; RECOLLECTION; SEPTEMBER-11; RETRIEVAL; KORSAKOFF; DEFICITS AB A flashbulb memory (FM) is a vivid, enduring memory for how one learned about a surprising, shocking event. It thus involves memory for the source of event information, as opposed to memory for the event itself Which brain regions are involved in FM, however, is uncertain. Although medial temporal lobe/diencephalic (MTL/D) damage impairs content or item memory, frontal lobe (FL) damage has been associated with impaired source memory. One would therefore expect that FM should depend on the FLs, although two recent reports do not support this idea. In the current study, we examined memory for the events of September 11th, and memory for the source of that information, in MT/D patients, FL patients, and healthy subjects. Only the MTL/D patients were impaired in long-term memory for the event itself measured after a 6 month retention interval. The FL patients, on the other hand, showed a selective deficit in source memory, although their memory for the target event was unimpaired. MTL/D and FL structures appear to play different roles in memory for flashbulb events. C1 Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. Univ Arizona, Dept Neurol, Tucson, AZ USA. So Arizona VA Healthcare Syst, Tucson, AZ USA. RP Davidson, PSR (reprint author), Baycrest Ctr Geriatr Care, Rotman Res Inst, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. EM Pdavidson@rotman-baycrest.on.ca RI Davidson, Patrick/F-6768-2013; OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIA NIH HHS [AG 14792, R01 AG014792, R01 AG014792-05]; NINDS NIH HHS [NS 26985, P50 NS026985] NR 49 TC 14 Z9 14 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 2005 VL 27 IS 7 BP 915 EP 929 DI 10.1080/13803390490919335 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 970GN UT WOS:000232293400012 PM 16183624 ER PT J AU Welt, CK Taylor, AE Fox, J Messerlian, GM Adams, JM Schneyer, AL AF Welt, CK Taylor, AE Fox, J Messerlian, GM Adams, JM Schneyer, AL TI Follicular arrest in polycystic ovary syndrome is associated with deficient inhibin A and B biosynthesis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LUTEINIZING-HORMONE; MESSENGER-RNA; STIMULATING-HORMONE; MENSTRUAL-CYCLE; GRANULOSA-CELLS; WOMEN; FOLLISTATIN; FOLLICLES; ACTIVIN; SERUM AB Context: Previous studies suggest that inhibin subunit expression is decreased in granulosa cells of women with polycystic ovary syndrome ( PCOS). Objective: The objective of this study was to test the hypothesis that inhibin A and inhibin B protein concentrations are also decreased in PCOS follicles. Design: The design was a parallel study. Setting: The study was performed at an in vitro fertilization suite. Participants: We studied women with regular cycles (n = 36) and women with PCOS (n = 8). Interventions: Follicular fluid was aspirated from the follicles of women with PCOS (n = 14 follicles) and from women with regular cycles at various times during the follicular phase (n = 50 follicles). Main Outcome Measure: Inhibin A and B concentrations from PCOS follicles were compared with those in size-matched follicles, dominant follicles (>= 10 mm), and subordinate follicles from regularly cycling women. Results: Inhibin A(220 +/- 38 vs. 400 +/- 72 IU/ml; P < 0.05) and inhibin B (75.4 +/- 10.4 vs. 139 +/- 26 ng/ml; P < 0.05) concentrations were lower in the follicular fluid of PCOS follicles compared with those of size-matched follicles from regularly cycling women. Inhibin A was also lower in the follicular fluid of PCOS compared with subordinate follicles from normal women (577 +/- 166 IU/ml; P < 0.05). Inhibin A concentrations increased with increasing follicle size, resulting in significantly higher follicular fluid concentrations in dominant follicles from normal women compared with PCOS follicles ( 2298 +/- 228 IU/ml; P < 0.05). Conclusions: These data demonstrate that inhibin A and inhibin B concentrations are significantly reduced in the follicular fluid of women with PCOS compared with those in the follicular fluid of size-matched follicles from normal women, consistent with the decreased inhibin subunit mRNA expression in previous studies. These findings point to the potential importance of inhibins in normal follicle development and suggest that inhibin deficiency may play a role in the follicle arrest associated with PCOS. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Women & Infants Hosp Rhode Isl, Dept Pathol & Lab Med, Providence, RI 02903 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504; Messerlian, Geralyn/0000-0002-9440-3411 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [U01-HD-44417, U54-HD-29164] NR 38 TC 47 Z9 51 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2005 VL 90 IS 10 BP 5582 EP 5587 DI 10.1210/jc.2005-0695 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971FJ UT WOS:000232367400010 PM 16030174 ER PT J AU Johnsen, S Dolan, SE Fitch, KV Killilea, KM Shifren, JL Grinspoon, SK AF Johnsen, S Dolan, SE Fitch, KV Killilea, KM Shifren, JL Grinspoon, SK TI Absence of polycystic ovary syndrome features in human immunodeficiency virus-infected women despite significant hyperinsulinemia and truncal adiposity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE; BODY-COMPOSITION; BINDING GLOBULIN; ANTIRETROVIRAL THERAPY; OBESE WOMEN; ANDROGEN; GONADOTROPIN; MEN; PREVALENCE; METFORMIN AB Context: HIV-infected women increasingly demonstrate insulin resistance and fat redistribution characterized by relative truncal adiposity. It is unknown whether insulin resistance and truncal adiposity are associated with features of the polycystic ovary syndrome in this population. Objective: The objective of the study was to characterize ovarian morphology and reproductive indices in a large cohort of HIV-infected women in comparison with healthy age-and body mass index-matched control subjects. Setting: The study was conducted at an academic medical center. Subjects: Eighty-eight HIV-infected women were compared with 94 age-and body mass index-matched healthy control subjects. Main Outcome Measures: Androgen, SHBG, and gonadotropin levels and ovarian morphology were measured. Results: HIV-infected subjects demonstrated increased visceral adipose tissue (VAT) (101 +/- 6 vs. 71 +/- 5 cm(2); P < 0.0001), increased VAT to sc adipose tissue ratio, and a trend toward decreased abdominal sc adipose tissue. Fasting insulin (12 +/- 1 vs. 6 +/- 1 mu IU/ml; P < 0.001) and 2-h glucose (124 +/- 4 vs. 106 +/- 4 mg/dl; P = 0.001) were also significantly increased in the HIV-infected women, compared with control subjects, respectively. Despite significant hyperinsulinemia and visceral adiposity, HIV-infected women did not demonstrate irregular menses or an increased number of small ovarian follicles (8.0 +/- 0.9 vs. 8.5 +/- 0.7 follicles; P = 0.65, HIV-infected vs. controls). Rather, SHBG (124 +/- 10 vs. 84 +/- 4 nmol/liter; P < 0.001) was increased significantly in HIV-infected women, and free testosterone by equilibrium dialysis was significantly reduced (2.2 +/- 0.2 vs. 2.7 +/- 0.2 pg/ml; P = 0.04), as was LH to FSH ratio (0.62 +/- 0.05 vs. 0.83 +/- 0.07; P = 0.03). Menstrual function, androgen levels, and ovarian morphology by ultrasonography were not different between HIV-infected women and healthy controls. Conclusions: These data demonstrate that among HIV-infected subjects with severe abdominal fat accumulation and hyperinsulinemia, common features of polycystic ovary syndrome are not seen. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. EM sgrinspoon@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R01 DK59535] NR 36 TC 7 Z9 7 U1 0 U2 0 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 OCT PY 2005 VL 90 IS 10 BP 5596 EP 5604 DI 10.1210/jc.2005-1083 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971FJ UT WOS:000232367400012 PM 16076939 ER PT J AU Canavan, B Salem, RO Schurgin, S Koutkia, P Lipinska, I Laposata, M Grinspoon, S AF Canavan, B Salem, RO Schurgin, S Koutkia, P Lipinska, I Laposata, M Grinspoon, S TI Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; OBESE SUBJECTS; SERUM LEPTIN; P-SELECTIN; PLASMA LEPTIN; NORMAL-WEIGHT; HEALTHY; HUMANS; DEFICIENCY; RISK AB Context: Leptin is a nutritionally regulated adipocyte-derived cytokine. Previous studies in obese patients have demonstrated increased inflammatory markers and increased platelet aggregation in association with leptin. However, the effects of leptin administration on markers of inflammation and platelet aggregation in a human model of undernutrition have not previously been studied. Objective: The objective of the study was to investigate markers of inflammation, platelet activation, and platelet aggregation in a model of caloric deprivation and increased leptin sensitivity. Design: This study was a randomized, placebo-controlled study conducted between November 2002 and November 2003. Setting: The study was conducted at an inpatient care setting at the General Clinical Research Center. Participants: Twenty healthy, young (18-35 yr old), normal-weight ( body mass index, 20-26 kg/m(2)) women were recruited from local advertisements. No subjects withdrew due to adverse effects. Intervention: The effects of physiological recombinant methionyl human leptin or identical placebo administration were investigated over a 4-d fast. Main Outcome Measures: The primary outcome measures for this study were C-reactive protein (CRP) and indices of platelet activity. Results: Leptin administration prevented the fasting-induced decline in leptin (P < 0.05 vs. placebo at each time point). Leptin administration increased CRP (6.3 +/- 2.4 vs. 0.7 +/- 0.3 mg/ liter; P = 0.04), circulating P-selectin (11.6 +/- 10.2 vs. -28.9 +/- 15.6 ng/ml; P = 0.04), and induction of platelet aggregation (5.8 +/- 2.6 vs. -2.7 +/- 2.9%, P = 0.04, percent maximum plat elet aggregation) relative to placebo administration ( change in leptin vs. change in placebo, respectively, for each variable). Leptin tended to increase serum amyloid A [0.1 +/- 10.2 vs. -0.3 +/- 0.1 log(10) (ng/ml); P = 0.07], and the changes in serum amyloid A and CRP were highly correlated (r = 0.83; P < 0.0001). No changes in TNF alpha, IL-6, IL-10, plasminogen activator inhibitor-1, haptoglobin, intercellular adhesion molecule, or vascular cell adhesion molecule were seen between the groups. Conclusions: Our data provide evidence that physiological leptin administration stimulates inflammatory and platelet responses in humans during caloric deprivation. C1 Harvard Univ, Program Nutr Metab, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Lab Med,Pathol Dept, Boston, MA 02114 USA. Boston Univ, Med Ctr, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Grinspoon, S (reprint author), Harvard Univ, Program Nutr Metab, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01 RR01066]; NIDDK NIH HHS [P30 DK40561] NR 30 TC 54 Z9 59 U1 0 U2 1 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 OCT PY 2005 VL 90 IS 10 BP 5779 EP 5785 DI 10.1210/jc.2005-0780 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971FJ UT WOS:000232367400040 PM 16076944 ER PT J AU Rasouli, N Hale, T Kahn, SE Spencer, HJ Elbein, SC AF Rasouli, N Hale, T Kahn, SE Spencer, HJ Elbein, SC TI Effects of short-term experimental insulin resistance and family history of diabetes on pancreatic beta-cell function in nondiabetic individuals SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE-TOLERANCE; NICOTINIC-ACID; ISLET ADAPTATION; SECRETION; SENSITIVITY; PATHOGENESIS; MELLITUS; COMPENSATION; HERITABILITY; DYSFUNCTION AB Context: Normal glucose homeostasis is maintained despite reductions in insulin sensitivity by increasing insulin secretion. This ability to compensate for reduced insulin sensitivity is highly heritable, but the mechanisms for this compensation or its failure in type 2 diabetes (T2DM) are unknown. Objective: The objective of this study was to test whether individuals with a family history of T2DM have a fixed decrease in beta-cell mass or function that would be revealed as an impaired insulin secretory response to short-term insulin resistance. Design: Glucose tolerance, insulin sensitivity (SI), and insulin response to iv glucose (AIR(G)) were compared in nondiabetic individuals with and without a family history of diabetes before and after nicotinic acid (NA) treatment. Setting: This study was performed at the Ambulatory General Clinical Research Center. Subjects: Healthy, nonobese, nondiabetic individuals with or without a family history of T2DM were studied. Interventions: Oral NA was given, with a final dose of 2 g/d, for at least 7 d. Main Outcome Measure: The main outcome measure was the disposition index (insulin sensitivity X insulin response) in response to NA. Results: Postchallenge plasma glucose levels rose during NA therapy regardless of family history. Neither group adequately increased their AIRG to maintain the disposition index. Family members did not differ from controls at baseline or after NA treatment for any outcome measure, but only 28 of 52 subjects experienced a 25% or greater fall in SI with NA treatment. Conclusions: Short-term beta-cell compensation to NA-induced insulin resistance was incomplete and did not differ by genetic predisposition. A genetic defect controlling beta-cell growth in response to chronic insulin resistance better explains differences in the ability to compensate for insulin resistance than an inherited, fixed defect in beta-cell mass. C1 Cent Arkansas Vet Healthcare Syst, Med & Res Serv, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Publ Hlth, Div Endocrine, Dept Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Biostat, Little Rock, AR 72205 USA. Vet Affairs Puget Sound Healthcare Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98108 USA. RP Elbein, SC (reprint author), Cent Arkansas Vet Healthcare Syst, Med & Res Serv, Endorcinol 111J-LR, Little Rock, AR 72205 USA. EM elbeinstevenc@uams.edu FU NCRR NIH HHS [M01-RR-14288]; NIDDK NIH HHS [DK-02654, DK-39311] NR 32 TC 20 Z9 21 U1 0 U2 1 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 OCT PY 2005 VL 90 IS 10 BP 5825 EP 5833 DI 10.1210/jc.2005-0048 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971FJ UT WOS:000232367400047 PM 16091496 ER PT J AU Letai, A AF Letai, A TI Pharmacological manipulation of Bcl-2 family members to control cell death SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID CYTOCHROME-C RELEASE; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; PROTOTYPE CANCER THERAPEUTICS; INDUCED CONFORMATIONAL-CHANGE; BH3-ONLY PROTEINS; TRANSGENIC MICE; BH3 DOMAIN; IN-VIVO; PROAPOPTOTIC ACTIVITY; CHROMOSOMAL BREAKPOINT AB The commitment to programmed cell death involves complex interactions among pro- and antiapoptotic members of the Bcl-2 family of proteins. The physiological result of a decision by these proteins to undergo cell death is permeabilization of the mitochondrial outer membrane. Pharmacologic manipulation of proteins in this family appears both feasible and efficacious, whether the goal is decreased cell death, as in ischemia of the myocardium or brain, or increased cell death, as in cancer. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu FU NCI NIH HHS [K08 CA10254] NR 119 TC 93 Z9 100 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2005 VL 115 IS 10 BP 2648 EP 2655 DI 10.1172/JC126250 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 971IE UT WOS:000232376600012 PM 16200198 ER PT J AU Motto, DG Chauhan, AK Zhu, GJ Homeister, J Lamb, CB Desch, KC Zhang, WR Tsai, HM Wagner, DD Ginsburg, D AF Motto, DG Chauhan, AK Zhu, GJ Homeister, J Lamb, CB Desch, KC Zhang, WR Tsai, HM Wagner, DD Ginsburg, D TI Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; HEMOLYTIC-UREMIC SYNDROME; CHROMOSOME SUBSTITUTION STRAINS; VONWILLEBRAND-FACTOR MULTIMERS; FACTOR-VIII; GENE; MUTATIONS; ADAMTS-13; IDENTIFICATION AB Thrombotic thrombocytopenic purpura (TTP) is a life-threatening illness caused by deficiency of the vWF-cleaving protease ADAMTS13. Here we show that ADAMTS13-deficient mice are viable and exhibit normal survival, although vWF-mediated platelet-endothelial interactions are significantly prolonged. Introduction of the genetic background CASA/Rk (a mouse strain with elevated plasma vWF) resulted in the appearance of spontaneous thrombocytopenia in a subset of ADAMTS13-deficient mice and significantly decreased survival. Challenge of these mice with shigatoxin (derived from bacterial pathogens associated with the related human disease hemolytic uremic syndrome) resulted in a striking syndrome closely resembling human TTP. Surprisingly, no correlation was observed between plasma vWF level and severity of TTP, implying the existence of TTP-modifying genes distinct from vWF. These data suggest that microbe-derived toxins (or possibly other sources of endothelial injury), together with additional genetic susceptibility factors, are required to trigger TTP in the setting of ADAMTS13 deficiency. C1 Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. CBR, Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Albert Einstein Coll Med, Dept Internal Med, New York, NY USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. RP Ginsburg, D (reprint author), Univ Michigan, Inst Life Sci 5028, 210 Washtenaw Ave, Ann Arbor, MI 48109 USA. EM ginsburg@umich.edu FU NCI NIH HHS [P30 CA046592, CA46592]; NHLBI NIH HHS [P01 HL057346, R01 HL062136-04, R01-HL062136, R01-HL39693, R01-HL72876, P01-HL057346, R01 HL039693, R01 HL062136, R01 HL072876, R37 HL041002]; NIAMS NIH HHS [AR20557]; PHS HHS [41002] NR 37 TC 192 Z9 200 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 OCT PY 2005 VL 115 IS 10 BP 2752 EP 2761 DI 10.1172/JCI26007 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 971IE UT WOS:000232376600026 PM 16200209 ER PT J AU Kennedy, AM Inada, M Krane, SM Christie, PT Harding, B Lopez-Otin, C Sanchez, LM Pannett, AAJ Dearlove, A Hartley, C Byrne, MH Reed, AAC Nesbit, MA Whyte, MP Thakker, RV AF Kennedy, AM Inada, M Krane, SM Christie, PT Harding, B Lopez-Otin, C Sanchez, LM Pannett, AAJ Dearlove, A Hartley, C Byrne, MH Reed, AAC Nesbit, MA Whyte, MP Thakker, RV TI MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMDMO) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EPI-METAPHYSEAL DYSPLASIA; GENETIC-HETEROGENEITY; COLLAGENASE-3 MMP-13; HUMAN CHONDROCYTES; STRUDWICK TYPE; DEGRADATION; ACTIVATION; EXPRESSION; CARTILAGE; CLASSIFICATION AB MMPs, which degrade components of the ECM, have roles in embryonic development, tissue repair, cancer, arthritis, and cardiovascular disease. We show that a missense mutation of MMP13 causes the Missouri type of human spondyloepimetaphyseal dysplasia (SEMDMO), an autosomal dominant disorder characterized by defective growth and modeling of vertebrae and long bones. Genome-wide linkage analysis mapped SEMDMO to a 17-cM region on chromosome 11q14.3-23.2 that contains a cluster of 9 MMP genes. Among these, MMP13 represented the best candidate for SEMDMO, since it preferentially degrades collagen type 11, abnormalities of which cause skeletal dysplasias that include Strudwick type SEMD. DNA sequence analysis revealed a missense mutation, F56S, that substituted an evolutionarily conserved phenylalanine residue for a serine in the proregion domain of MMP13. We predicted, by modeling MMP13 structure, that this F56S mutation would result in a hydrophobic cavity with misfolding, autoactivation, and degradation of mutant protein intracellularly. Expression of wild-type and mutant MMP13s in human embryonic kidney cells confirmed abnormal intracellular autoactivation and autodegradation of F56S MMP13 such that only enzymatically inactive, small fragments were secreted. Thus, the F56S mutation results in deficiency of MMP13, which leads to the human skeletal developmental anomaly of SEMDMO. C1 Univ Oxford, Churchill Hosp, OCDEM, Nuffield Dept Clin Med,Acad Endocrine Unit, Oxford OX3 7LJ, England. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Univ Oviedo, Inst Univ Oncol, Dept Bioquim, Oviedo, Spain. MRC, Human Genome Mapping Project Resource Ctr, Cambridge, England. Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, St Louis, MO USA. RP Thakker, RV (reprint author), Univ Oxford, Churchill Hosp, OCDEM, Nuffield Dept Clin Med,Acad Endocrine Unit, S Parks Rd, Oxford OX3 7LJ, England. EM rajesh.thakker@ndm.ox.ac.uk RI inada, masaki/D-1581-2013; Lopez-Otin, Carlos/C-6657-2013 OI inada, masaki/0000-0002-5066-8506; Lopez-Otin, Carlos/0000-0001-6964-1904 NR 50 TC 55 Z9 59 U1 2 U2 6 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 OCT PY 2005 VL 115 IS 10 BP 2832 EP 2842 DI 10.1172/JCI22900 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 971IE UT WOS:000232376600034 PM 16167086 ER PT J AU Maehr, R Mintern, JD Herman, E Lennon-Dumenil, AM Mathis, D Benoist, C Ploegh, HL AF Maehr, R Mintern, JD Herman, E Lennon-Dumenil, AM Mathis, D Benoist, C Ploegh, HL TI Cathepsin L is essential for onset of autoimmune diabetes in NOD mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MHC-CLASS-II; REGULATORY T-CELLS; COMPLEX CLASS-II; PANCREATIC LYMPH-NODES; INVARIANT CHAIN; ANTIGEN PRESENTATION; TRANSCRIPTION FACTOR; SURFACE EXPRESSION; DENDRITIC CELLS; IN-VIVO AB Lysosomal proteases generate peptides presented by class II MHC molecules to CD4(+) T cells. To determine whether specific lysosomal. proteases might influence the outcome of a CD4(+)T cell-dependent autoimmune response, we generated mice that lack cathepsin L (Cat L) on the autoimmune diabetes-prone NOD inbred background. The absence of Cat L affords strong protection from disease at the stage of pancreatic infiltration. The numbers of I-A(g7)-restricted CD4(+) T cells are diminished in Cat L-deficient mice, although a potentially diabetogenic T cell repertoire persists. Within the CD4(+)T cell compartments of Cat L-deficient mice, there is an increased proportion of regulatory T cells compared with that in Cat L-sufficient littermates. We suggest that it is this displaced balance of regulatory versus aggressive CD4(+) T cells that protects Cat L-deficient mice from autoimmune disease. Our results identify Cat L as an enzyme whose activity is essential for the development of type I diabetes in the NOD mouse. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ploegh, HL (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ploegh@hms.harvard.edu RI Lennon-Dumenil, Ana-Maria/I-6716-2016; OI Mintern, Justine/0000-0002-3797-8577 FU NCI NIH HHS [T32 CA 70083-07, T32 CA070083] NR 58 TC 49 Z9 50 U1 1 U2 2 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 OCT PY 2005 VL 115 IS 10 BP 2934 EP 2943 DI 10.1172/JCI25485 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 971IE UT WOS:000232376600045 PM 16184198 ER PT J AU Johnson, BE Janne, PAJ AF Johnson, BE Janne, PAJ TI Selecting patients for epidermal growth factor receptor inhibitor treatment: A FISH story or a tale of mutations? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CELL LUNG-CANCER; GENE COPY NUMBER; GEFITINIB SENSITIVITY; EGFR MUTATIONS; RESISTANCE; ERLOTINIB; PROTEIN; IMPACT C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, BE (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. NR 17 TC 36 Z9 38 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2005 VL 23 IS 28 BP 6813 EP 6816 DI 10.1200/JCO.2005.97.008 PG 4 WC Oncology SC Oncology GA 969KC UT WOS:000232232000001 PM 16145056 ER PT J AU Masciari, S Garber, JE AF Masciari, S Garber, JE TI Quality or quantity in the management of hereditary ovarian cancer risk: Is it really a trade-off? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PROPHYLACTIC OOPHORECTOMY; BRCA2 MUTATIONS; BREAST-CANCER; WOMEN; MENOPAUSE; LIFE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Masciari, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2005 VL 23 IS 28 BP 6817 EP 6819 DI 10.1200/JCO.2005.96.009 PG 3 WC Oncology SC Oncology GA 969KC UT WOS:000232232000002 PM 16157931 ER PT J AU Vanderwerker, LC Laff, RE Kadan-Lottick, NS McColl, S Prigerson, HG AF Vanderwerker, LC Laff, RE Kadan-Lottick, NS McColl, S Prigerson, HG TI Psychiatric disorders and mental health service use among caregivers of advanced cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FAMILY CAREGIVERS; SPOUSAL CAREGIVERS; CHRONIC STRESS; BREAST-CANCER; TERMINAL CARE; OF-LIFE; DEPRESSION; DISTRESS; DEMENTIA; DISEASE AB Purpose Despite research demonstrating the psychological burden of caregiving for advanced cancer patients, limited information exists on the prevalence of psychiatric disorders and mental health service use among these informal caregivers. Methods Two hundred informal caregivers of advanced cancer patients were interviewed and administered the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and an assessment of mental health service use. Results Thirteen percent of caregivers met criteria for a psychiatric disorder; 25% accessed treatment for mental health concerns since the patient's cancer diagnosis. The frequencies of current psychiatric disorders were as follows: panic disorder, 8.0% (95% Cl, 4.6% to 12.7%), major depressive disorder, 4.5% (95% Cl, 2.1% to 8.4%), post-traumatic stress disorder, 4.0% (95% Cl, 1.7% to 7.7%), and generalized anxiety disorder, 3.5% (95% Cl, 1.4% to 7.1%). Among caregivers with a current psychiatric disorder, 81% discussed mental health concerns with a health professional before the patient's cancer diagnosis compared with 46% after the diagnosis (McNemar test = 5.40; P =.02). Only 46% of caregivers with a current psychiatric disorder accessed mental health services. Caregivers who discussed mental health concerns with a clinician before the patient's cancer diagnosis (odds ratio [OR] = 3.51; 95% Cl, 1.42 to 8.71) and after the diagnosis (OR = 21.23; 95% Cl, 9.02 to 49.94) were more likely than caregivers not having these discussions to receive mental health services. Conclusion Many caregivers of advanced cancer patients either meet criteria or are being treated for psychiatric problems. Discussing mental health issues positively influences the receipt of mental health services and should be actively pursued in this vulnerable population. C1 Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Yale Univ, Sch Med, Dept Pediat, Sect Pediat Hematol & Oncol, New Haven, CT USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St,SW G440A, Boston, MA 02115 USA. EM holly_prigerson@dfci.harvard.edu FU NCI NIH HHS [CA106370, R01 CA106370, R01 CA106370-01, R01 CA106370-03]; NCRR NIH HHS [K12 RR017594, K12RR17594]; NIA NIH HHS [P30 AG021342, P30AG21342]; NIMH NIH HHS [MH56529, MH63892, R01 MH056529, R01 MH063892] NR 51 TC 101 Z9 102 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2005 VL 23 IS 28 BP 6899 EP 6907 DI 10.1200/JCO.2005.01.370 PG 9 WC Oncology SC Oncology GA 969KC UT WOS:000232232000014 PM 16129849 ER PT J AU Stearns, V Slack, R Greep, N Henry-Tilman, R Osborne, M Bunnell, C Ullmer, L Gallagher, A Cullen, J Gehan, E Hayes, DF Isaacs, C AF Stearns, V Slack, R Greep, N Henry-Tilman, R Osborne, M Bunnell, C Ullmer, L Gallagher, A Cullen, J Gehan, E Hayes, DF Isaacs, C TI Paroxetine is an effective treatment for hot flashes: Results from a prospective randomized clinical trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID BREAST-CANCER SURVIVORS; QUALITY-OF-LIFE; REPLACEMENT THERAPY; ADJUVANT BREAST; TAMOXIFEN; PREVENTION; WOMEN AB Purpose In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, place bo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters. Patients and Methods Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9. Results 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P =.0006 and P =.0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P =.002 and P =.004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P =.01). Conclusion Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer. C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Strang Cornell Breast Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. John Wayne Canc Inst, Santa Monica, CA USA. Arkansas Canc Res Ctr, Little Rock, AR USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI USA. RP Stearns, V (reprint author), Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,CRB 1M53, Baltimore, MD 21230 USA. EM vstearn1@jhmi.edu NR 30 TC 128 Z9 132 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 OCT 1 PY 2005 VL 23 IS 28 BP 6919 EP 6930 DI 10.1200/JCO.2005.10.081 PG 12 WC Oncology SC Oncology GA 969KC UT WOS:000232232000016 PM 16192581 ER PT J AU Wirth, LJ Haddad, RI Lindeman, NI Zhao, XJ Lee, JC Joshi, VA Norris, CM Posner, MR AF Wirth, LJ Haddad, RI Lindeman, NI Zhao, XJ Lee, JC Joshi, VA Norris, CM Posner, MR TI Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; LUNG-CANCER; TYROSINE KINASE; MUTATIONS; CYCLOOXYGENASE-2; THERAPY; GENE; CHEMOPREVENTION; COMBINATION; INDUCTION AB Purpose Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown. Patients and Methods Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily;, (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily. Results No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% Cl, 2% to 42%) achieved a confirmed partial response. Conclusion The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Pathol & Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wirth, LJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM lwirth@partners.org NR 23 TC 81 Z9 89 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2005 VL 23 IS 28 BP 6976 EP 6981 DI 10.1200/JCO.2005.02.4182 PG 6 WC Oncology SC Oncology GA 969KC UT WOS:000232232000022 PM 16172459 ER PT J AU Zhou, P Chen, MH McLeod, D Carroll, PR Moul, JW D'Amico, AV AF Zhou, P Chen, MH McLeod, D Carroll, PR Moul, JW D'Amico, AV TI Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MITOXANTRONE PLUS PREDNISONE; COMPETING RISK; ANTIGEN; RECURRENCE; SURVIVAL; FAILURE; DOCETAXEL; DATABASE; TRIAL; MEN AB Purpose We evaluated predictors of prostate cancer-specific mortality (PCSM) after prostate-specific antigen (PSA) failure after radical prostatectomy (RP) or radiation therapy (RT). Patients and Methods A total of M 59 men with clinically localized prostate cancer treated with RP (n = 498) or RT (n = 661) developed PSA failure, and they formed the study cohort. Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis, including post-treatment PSA doubling time (PSA-DT), Gleason score, and interval to PSA failure, could also predict time to PCSM after PSA failure. The cumulative incidence method was used to estimate PCSM after PSA failure. Results A post-RP PSA-DT of less than 3 months (hazard ratio [HR], 54.9; 95% Cl, 16.7 to 180), a post-RT PSA-DT of less than 3 months (HR, 12.8; 95% Cl, 7.0 to 23.1), and a biopsy Gleason score of 8 to 10 (HR, 6.1-1 95% Cl, 3.4 to 10.7) for patients treated with RT were significantly associated with PCSM. Post-RP estimated rates of PCSM 5 years after PSA failure were 31% (95% Cl, 17% to 45%) v 1% (95% Cl, 0% to 2%) for patients with PSA-DT of less than 3 months v >= 3 months. Post-RT estimated rates of PCSM 5 years after PSA failure were 75% (95% Cl, 59% to 92%) v 35% (95% Cl, 24% to 47%) for patients with a biopsy Gleason score of >= 8 v <= 7, respectively, and PSA-DT of less than 3 months; these rates were 15% (95% Cl, 0.8% to 28%) v 4% (95% Cl, 1 % to 6%), respectively, for patients with a PSA-DT >= 3 months. Conclusion Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score. These parameters may be useful in identifying patients for a randomized trial evaluating hormonal therapy with or without docetaxel. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg & Urol Serv, Bethesda, MD USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Duke Univ, Dept Urol, Durham, NC USA. RP Zhou, P (reprint author), 375 Longwood Ave, Boston, MA 02215 USA. EM pzhou@partners.org NR 33 TC 137 Z9 140 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 OCT 1 PY 2005 VL 23 IS 28 BP 6992 EP 6998 DI 10.1200/JCO.2005.01.2906 PG 7 WC Oncology SC Oncology GA 969KC UT WOS:000232232000024 PM 16192586 ER PT J AU Gruber, G Bonetti, M Nasi, ML Price, KN Castiglione-Gertsch, M Rudenstam, CM Holmberg, SB Lindtner, J Golouh, R Collins, J Crivellari, D Carbone, A Thurlimann, B Simoncini, E Fey, MF Gelber, RD Coates, AS Goldhirsch, A AF Gruber, G Bonetti, M Nasi, ML Price, KN Castiglione-Gertsch, M Rudenstam, CM Holmberg, SB Lindtner, J Golouh, R Collins, J Crivellari, D Carbone, A Thurlimann, B Simoncini, E Fey, MF Gelber, RD Coates, AS Goldhirsch, A TI Prognostic value of extracapsular tumor spread for locoregional control in premenopausal patients with node-positive breast cancer treated with classical cyclophosphamide, methotrexate, and fluorouracil: Long-term observations from international breast cancer study group trial VI SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY; EXTRANODAL EXTENSION; COMPETING RISK; IRRADIATION; RECURRENCE; METASTASES; THERAPY; MASTECTOMY; WOMEN AB Purpose We sought to determine retrospectively whether extracapsular spread (ECS) might identify a subgroup that could benefit from radiotherapy after mastectomy, especially patients with 1 to 3 positive lymph nodes (LN1-3+). Patients and Methods 475 premenopausal women with node-positive breast cancer to three, six, We randomized 1 or nine courses of "classical" CMF (cyclophosphamide, methotrexate, and fluorouracil). After a review of all pathology forms, 933 patients (63%) had information on the presence or absence of ECS. ECS was present in 49.5%. The median follow-up was 10 years. In univariate analyses, ECS was associated with worse disease-free survival QFS) and overall survival (OS). In multivariate analyses adjusting for tumor size, vessel invasion, surgery type, and age group, ECS remained significant (DFS: hazard ratio, 1.61; 95% Cl, 1.34 surgery type r, to 1.93; P <.0001; OS: 1.67; 95% Cl, 1.34 to 2.08; P <.0001). However, ECS was not significant when the number of positive nodes was added. The locoregional failure rate distant failure (LRF +/- distant failure) within 10 years was estimated at 19% (2%) without versus 27% (+/- 2%) with ECS. The difference was statistically significant in univariate ECS, but not after adjusting for the number of positive nodes. No independent effect of analyses ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with OS ECS on DFS with mastectomy without radiotherapy. Conclusion Our results do not support an independent prognostic value of ECS, nor its use as an indication for irradiation in premenopausal patients with LN1-3+ treated with classical CMF. However, we could not examine whether extensive ECS is of prognostic importance. C1 Kantonsspital Aarau, Inst Radiat Oncol, CH-5001 Aarau, Switzerland. Inselspital Bern, Dept Radiat Oncol, Bern, Switzerland. Inselspital Bern, Inst Med Oncol, Bern, Switzerland. IBCSG Coordinating Ctr, Bern, Switzerland. Kantonsspital, St Gallen, Switzerland. Oncol Inst So Switzerland, Lugano, Switzerland. Oncol Inst So Switzerland, Mendrisio, Switzerland. Oncol Inst So Switzerland, Bellinzona, Switzerland. Dana Farber Canc Inst, IBCGS Stat Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Univ Gothenburg, Sahlgrenska Hosp, W Swedish Breast Canc Study Grp, Gothenburg, Sweden. SU Moelndals Hosp, Dept Surg, Molndal, Sweden. Inst Oncol, Ljubljana, Slovenia. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Oncol Med Spedali Civili, Brescia, Italy. European Inst Oncol, Milan, Italy. RP Gruber, G (reprint author), Kantonsspital Aarau, Inst Radiat Oncol, Tellstr, CH-5001 Aarau, Switzerland. EM guenther.gruber@ksa.ch FU NCI NIH HHS [CA-75362] NR 28 TC 16 Z9 17 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 OCT 1 PY 2005 VL 23 IS 28 BP 7089 EP 7097 DI 10.1200/JCO.2005.08.123 PG 9 WC Oncology SC Oncology GA 969KC UT WOS:000232232000036 PM 16192592 ER PT J AU Anderson, KC Pazdur, R Farrell, AT AF Anderson, KC Pazdur, R Farrell, AT TI Development of effective new treatments for multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROTEASOME INHIBITOR PS-341; PHASE-I TRIAL; MALIGNANCIES; BORTEZOMIB; GROWTH C1 Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. US FDA, Off Oncol Drug Prod, Rockville, MD 20857 USA. US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 13 TC 13 Z9 15 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2005 VL 23 IS 28 BP 7207 EP 7211 DI 10.1200/JCO.2005.02.4950 PG 5 WC Oncology SC Oncology GA 969KC UT WOS:000232232000049 PM 16145064 ER PT J AU Brawman-Mintzer, O Knapp, RG Nietert, PJ AF Brawman-Mintzer, O Knapp, RG Nietert, PJ TI Adjunctive risperidone in generalized anxiety disorder: A double-blind, placebo-controlled study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 16th Congress of the European-College-of-Neuropsychopharmacology CY SEP 20-24, 2003 CL PRAGUE, CZECH REPUBLIC SP European Coll Neuropsychopharmacol ID DEPRESSION SCALE AB Objective: Although significant advances have been made in recent years in the treatment of generalized anxiety disorder (GAD), many patients remain symptomatic despite ongoing treatment, underscoring the need for adjunctive new treatments to help improve response. Method: Forty patients with a primary diagnosis of DSM-IV GAD, who continued to experience GAD symptoms despite current anxiolytic treatment of at least 4 weeks' duration, as evidenced by Hamilton Rating Scale for Anxiety (HAM-A) total score >= 18 and Clinical Global Impressions-Severity of Illness scale score of moderate or greater, completed a 1-week screening phase and were then randomly assigned to 5 weeks of double-blind adjunctive treatment with placebo or risperidone at flexible doses of 0.5 to 1.5 mg/day. Patients continued to take their anxiolytics throughout the study. The study was conducted from June 2001 through March 2003. Results: Adjunctive risperidone was associated with statistically significant improvements in core anxiety symptoms, as demonstrated by greater reductions in HAM-A total scores (p = .034) and HAM-A psychic anxiety factor scores (p = .047) compared with placebo. Although change scores on other outcome variables, including response rates, were higher in the risperidone group, differences did not achieve statistical significance. Conclusion: Study findings suggest that risperidone at low doses may represent a useful tool in the management of symptomatic GAD patients. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Brawman-Mintzer, O (reprint author), 5900 Core Rd,Suite 203, Charleston, SC 29406 USA. EM mintzero@musc.edu OI Nietert, Paul/0000-0002-3933-4986 NR 20 TC 79 Z9 81 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2005 VL 66 IS 10 BP 1321 EP 1325 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 978ZJ UT WOS:000232911500016 PM 16259547 ER PT J AU Papakostas, GI Petersen, TJ Kinrys, G Burns, AM Worthington, JJ Alpert, JE Fava, M Nierenberg, AA AF Papakostas, GI Petersen, TJ Kinrys, G Burns, AM Worthington, JJ Alpert, JE Fava, M Nierenberg, AA TI Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIPSYCHOTIC-DRUG; 7-(4-<4-(2,3-DICHLOROPHENYL)-1-PIPERAZINYL>BUTYLOXY)-3,4-DIHYDRO-2(1H)-Q UINOLIN OPC-14597; SCHIZOAFFECTIVE DISORDER; RESIDUAL SYMPTOMS; PARTIAL AGONIST; PLACEBO; SCHIZOPHRENIA; DOPAMINE; EFFICACY; RECEPTOR AB Background: Due to their favorable side effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Aripiprazole, an atypical antipsychotic agent with partial dopaminergic and serotonin 1, receptor agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study was to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). Method: 12 patients (mean +/- SD age 46.6 +/- 11.3 years, 66.7% female) with major depressive disorder (MDD) diagnosed by use of the Structured Clinical Interview for DSM-IV-Axis I Disorders, who had failed to experience a clinical response following an adequate trial of an SSRI, were treated with open-label aripiprazole in addition to their SSRI for 8 weeks. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline-endpoint) as measured by the 17-item Hamilton Rating Scale for Depression total score. Data were collected from August 2003 to July 2004. esults: 9/12 (75.0%) patients completed the trial. Using a completer analysis, 5/9 (55.6%) patients were classified as responders. An intent to-treat (ITT) analysis resulted in 7 responders (58.3%). The overall proportion of remitters was 3/9 (33.3%) using a completer analysis and 5/12 (41.7%) using the ITT analysis. Aripiprazole administration appeared safe, with no severe adverse events observed in any of the study participants. Conclusions: These results suggest a possible augmentation role for aripiprazole when used in conjunction with SSRIs in SSRI-resistant MDD. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Cambridge Hlth Alliance, Anxiety Disorders Res Program, Cambridge, England. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WAC 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 NR 35 TC 88 Z9 92 U1 1 U2 4 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 OCT PY 2005 VL 66 IS 10 BP 1326 EP 1330 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 978ZJ UT WOS:000232911500017 PM 16259548 ER PT J AU Perlis, RH Ganz, DA Avorn, J Schneeweiss, S Glynn, RJ Smoller, JW Wang, PS AF Perlis, RH Ganz, DA Avorn, J Schneeweiss, S Glynn, RJ Smoller, JW Wang, PS TI Pharmacogenetic testing in the clinical management of schizophrenia - A decision-analytic model SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID CLOZAPINE-INDUCED AGRANULOCYTOSIS; NEUROLEPTIC-RESISTANT SCHIZOPHRENIA; COST-EFFECTIVENESS; ATYPICAL ANTIPSYCHOTICS; HOSPITALIZED-PATIENTS; DRUG RESPONSE; METAANALYSIS; MORTALITY; AZATHIOPRINE; POLYMORPHISM AB Clinical application of pharmacogenetic testing has been proposed as a means of improving treatment outcomes in psychiatry. The identification of a putative genetic test for better clozapine response in schizophrenia offers an opportunity to evaluate the cost-effectiveness of such testing. The authors performed a cost-effectiveness analysis of a genetic test that may identify individuals with greater likelihood of responding to clozapine treatment. We modeled a target population of schizophrenia patients in an acute psychotic episode, using a lifetime time horizon and societal perspective. Outcome measures included life expectancy, quality-adjusted life expectancy, costs, and incremental cost-effectiveness. Effects of variations in testing parameters were also examined. For a 30-year-old with schizophrenia, applying the pharmacogenetic test and treating those predicted to respond to clozapine with clozapine-first cost US$47,705 per additional quality-adjusted life-year, compared with treating all patients with conventional agents and reserving clozapine for treatment-resistant patients. In 1-way sensitivity analyses, test sensitivity and cost had the greatest impact on the incremental cost-effectiveness. We conclude that pharmacogenetic tests may achieve utility in clinical psychiatry, although their cost-effectiveness depends on several clinical parameters. More consistent reporting of test parameters such as sensitivity and specificity would greatly facilitate assessment of future pharmacogenetic studies. C1 Massachusetts Gen Hosp, Dept Psychiat, Pharmacogenom Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pharmacogenom Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org RI Schneeweiss, Sebastian/C-2125-2013 NR 62 TC 34 Z9 37 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2005 VL 25 IS 5 BP 427 EP 434 DI 10.1097/01.jcp.0000177553.59455.24 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 970EH UT WOS:000232287500007 PM 16160617 ER PT J AU Fava, M Alpert, J Nierenberg, AA Mischoulon, D Otto, MW Zajecka, J Murck, H Rosenbaum, JF AF Fava, M Alpert, J Nierenberg, AA Mischoulon, D Otto, MW Zajecka, J Murck, H Rosenbaum, JF TI A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID CLINICAL-TRIALS; AUGMENTATION; LITHIUM AB Objective: This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort wit both placebo and fluoxetine. Method: After a I-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate. Results: One hundred thirty-five patients (57% women; mean age, 37.3 +/- 11.0; mean HAMD-17, 19.7 +/- 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean +/- SD, 10.2 +/- 6.6) compared with the fluoxetine group (n = 47; 13.3 +/- 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 +/- 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 < 8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated. Conclusion: St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo. C1 Massachusetts Gen Hosp, Depres Clin & Res Program, Boston, MA 02114 USA. Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. Lichtwer Pharma AG, D-13435 Berlin, Germany. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depres Clin & Res Program, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM mfava@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 15 TC 68 Z9 74 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2005 VL 25 IS 5 BP 441 EP 447 DI 10.1097/01.jcp.0000178416.60426.29 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 970EH UT WOS:000232287500009 PM 16160619 ER PT J AU Sachdeva, M Frambach, GE Crowson, AN Deng, AC Mihm, MC Magro, CM AF Sachdeva, M Frambach, GE Crowson, AN Deng, AC Mihm, MC Magro, CM TI De novo intraepidermal epithelioid melanocytic dysplasia as a marker of the atypical mole phenotype - a clinical and pathological study of 75 patients SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID MALIGNANT-MELANOMA; FAMILY-HISTORY; NEVI; RISK; MANAGEMENT; LESIONS; P53 AB Background: We encountered a distinctive pattern of dysplastic intraepidermal melanocytic proliferation, which defies classification as a dysplastic melanocytic nevus, but in which the morphologic features fall short of a diagnosis of melanoma in situ. We designate such lesions as de novo intraepidermal epithelioid melanocytic dysplasia. Methods: From 75 patients, 82 skin biopsies were encountered that showed this distinctive morphology. Hematoxylin- and eosin-stained histologic sections were studied and the features were correlated with personal and family histories of dysplastic nevi and melanoma. Results: The diagnosis of de novo melanocytic dysplasia was made in 27 male patients and 48 female patients (mean age: 44 years). The histologic hallmark was a pagetoid (single-cell) array of moderately to severely atypical epithelioid melanocytes within the epidermis. Seventy-three lesions were located on sun-exposed skin and nine on sun-protected skin. In 41 patients, there was an atypical mole phenotype, whereas 20 patients had a prior or subsequent diagnosis of melanoma with five of 16 patients questioned revealing a family history of melanoma. Conclusions: De novo intraepidermal epithelioid melanocytic dysplasia is a distinct entity associated with an atypical mole phenotype and a personal and/or family history of melanoma. C1 Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Ohio Univ, Coll Osteopath Med, Athens, OH 45701 USA. Univ Oklahoma, Tulsa, OK USA. Reg Med Labs, Tulsa, OK USA. Maryland Univ Med Syst, Dept Dermatol, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Magro, CM (reprint author), Ohio State Univ, Dept Pathol, N305 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM magro-1@medctr.osu.edu NR 21 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 2005 VL 32 IS 9 BP 622 EP 628 DI 10.1111/j.0303-6987.2005.00314.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA 965LC UT WOS:000231951000005 PM 16176300 ER PT J AU Marsh, R Nadel, ES Brown, DFM AF Marsh, R Nadel, ES Brown, DFM TI Multisystem organ failure SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID GAS-GANGRENE; PATHOGENESIS C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2005 VL 29 IS 3 BP 331 EP 334 DI 10.1016/j.jemermed.2005.06.008 PG 4 WC Emergency Medicine SC Emergency Medicine GA 969VE UT WOS:000232262600014 PM 16183454 ER PT J AU Andrikopoulos, S Massa, CM Aston-Mourney, K Funkat, A Fam, BC Hull, RL Kahn, SE Proietto, J AF Andrikopoulos, S Massa, CM Aston-Mourney, K Funkat, A Fam, BC Hull, RL Kahn, SE Proietto, J TI Differential effect of inbred mouse strain (C57BL/6, DBA/2, 129T2) on insulin secretory function in response to a high fat diet SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GENETIC BACKGROUND DETERMINES; INDUCED OBESITY; DIABETES LOCUS; BETA-CELLS; MICE; RESISTANCE; GLUCOSE; EXPRESSION; SENSITIVITY; MECHANISMS AB The increasing production of genetically-modified mouse models has necessitated studies to determine the inherent physiological characteristics of commonly used mouse strains. In this study we examined insulin secretory function in response to an intravenous bolus of glucose or glucose plus arginine in anesthetized C57BL/6, DBA/2 and 129T2 mice fed either a control or high fat diet for 6 weeks. The results show that 129T2 mice had higher fasting plasma glucose levels and lower fasting plasma insulin levels compared with C57BL/6 and DBA/2 mice regardless of diet. Furthermore, 129T2 mice were glucose intolerant and secreted significantly less insulin in response to glucose and glucose plus arginine irrespective of diet compared with the other two strains of mice. DBA/2 mice hypersecreted insulin in response to glucose and glucose plus arginine compared with C57BL/6 and 129T2 mice. Moreover while first phase insulin secretion was appropriately increased in response to the high fat diet in C57BL/6 and 129T2 mice, this was not the case for DBA/2 mice. Mean islet area was decreased in response to a high fat diet in DBA/2 mice, while there was no dietary effect on the other two strains. This study highlights the inherent genetic differences that exist among seemingly normal strains of mice that are commonly used to make transgenic and knockout mice. Understanding these differences will provide researchers with the information to choose the appropriate genetic background on which to express their particular genetic alteration. C1 Univ Melbourne, Dept Med AH NH, Heidelberg Repatriat Hosp, Heidelberg Heights, Vic 3081, Australia. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Andrikopoulos, S (reprint author), Univ Melbourne, Dept Med AH NH, Heidelberg Repatriat Hosp, 300 Waterdale Rd, Heidelberg Heights, Vic 3081, Australia. EM sof@unimelb.edu.au RI Proietto, Joseph/B-3780-2012; OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NIDDK NIH HHS [DK-17047] NR 35 TC 71 Z9 74 U1 2 U2 5 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2005 VL 187 IS 1 BP 45 EP 53 DI 10.1677/joe.1.06333 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 976DY UT WOS:000232714200005 PM 16214940 ER PT J AU Perry, SF Gilmour, KM Swenson, ER Vulesevic, B Chew, SF Ip, YK AF Perry, SF Gilmour, KM Swenson, ER Vulesevic, B Chew, SF Ip, YK TI An investigation of the role of carbonic anhydrase in aquatic and aerial gas transfer in the African lungfish Protopterus dolloi SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE carbon dioxide excretion; oxygen uptake; gill; lung; acetazolamide; benzolamide; breathing; lungfish; Protopterus dolloi; carbonic anhydrase ID TROUT ONCORHYNCHUS-MYKISS; SOUTH-AMERICAN LUNGFISH; CO2 EXCRETION; RAINBOW-TROUT; RESPIRATORY PROPERTIES; LEPIDOSIREN-PARADOXA; HCO3-DEHYDRATION; EXCHANGE ORGANS; ANION-EXCHANGE; BLOOD AB Experiments were performed on bimodally breathing African lungfish Protopterus dolloi to examine the effects of inhibition of extracellular vs total (extracellular and intracellular) carbonic anhydrase (CA) activity on pulmonary and branchial/cutaneous gas transfer. In contrast to previous studies on Protopterus, which showed that the vast majority of CO2 is excreted into the water through the gill and/or skin whereas O-2 uptake largely occurs via the lung, P. dolloi appeared to use the lung for the bulk of both 0, uptake (91.0 +/- 2.9%) and CO2 excretion (76.0 +/- 6.6%). In support of the lung as the more important site Of CO2 transfer, aerial hypercapnia (P-CO2=40 mmHg) caused a significant rise in partial pressure of arterial blood CO2 (Pa-CO2) whereas a similar degree of aquatic hypercapnia was without effect on Pa-CO2. Intravascular injection of low levels (1.2 mg kg(-1)) of the slowly permanent CA inhibitor, benzolamide, was without effect on red blood cell CA activity after 30 min, thus confirming its suitability as a short-term selective inhibitor of extracellular CA. Benzolamide treatment did not affect CO2 excretion, blood acid-base status or any other measured variable within the 30 min measurement period. Injection of the permeant CA inhibitor acetazolamide (30 mg kg(-1)) resulted in the complete inhibition of red cell CA activity within 10 min. However, CO2 excretion (measured for 2 h after injection) and arterial blood acid-base status (assessed for 24 h after injection) were unaffected by acetazolamide treatment. Intra-arterial injection of bovine CA (2 mg kg(-1)) caused a significant increase in overall CO2 excretion (from 0.41 +/- 0.03 to 0.58 +/- 0.03 mmol kg(-1) h(-1)) and an increase in air breathing frequency (from 19.0 +/- 1.3 to 24.7 +/- 1.8 breaths min(-1)) that was accompanied by a slight, but significant, reduction in Pa-CO2 (from 21.6 +/- 1.6 to 19.6 +/- 1.8 mmHg). The findings of this study are significant because they (i) demonstrate that, unlike in other species of African lungfish that have been examined, the gill/skin is not the major route Of CO2 excretion in P. dolloi, and (ii) suggest that CO2 excretion in Protopterus may be less reliant on carbonic anhydrase than in most other fish species. C1 Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Nanyang Technol Univ, Natl Inst Educ, Dept Nat Sci, Singapore, Singapore. Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore. RP Perry, SF (reprint author), Univ Ottawa, Dept Biol, 150 Louis Pasteur, Ottawa, ON K1N 6N5, Canada. EM sfperry@science.uottawa.ca RI Ip, Yuen Kwong/H-8041-2012; Chew, Shit Fun/I-2248-2012 NR 54 TC 25 Z9 26 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD OCT PY 2005 VL 208 IS 19 BP 3805 EP 3815 DI 10.1242/jeb.01780 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 981ZT UT WOS:000233127200026 PM 16169956 ER PT J AU Shekelle, PG Hardy, M Morton, SC Venuturupalli, S Favreau, J Hilton, LK AF Shekelle, PG Hardy, M Morton, SC Venuturupalli, S Favreau, J Hilton, LK TI Are Ayurvedic herbs for diabetes effective? SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID GYMNEMA-SYLVESTRE; CONTROLLED TRIALS; LEAF EXTRACT; MELLITUS; QUALITY; BIAS; METAANALYSES; PRINCIPLES AB Objective To evaluate and synthesize the evidence on the effect of Ayurvedic therapies for diabetes mellitus. Design Systematic review of trials. Measurements and main results We found no study that assessed Ayurvedic as a system of care. Botanical therapy was by far the most commonly studied Ayurvedic treatment. Herbs were studied either singly or as formulas. In all, 993 titles in Western computerized databases and 318 titles identified by hand-searching journals in India were examined, yielding 54 articles reporting the results of 62 studies. The most-studied herbs were G sylvestre, C indica, fenugreek, and Eugenia jambolana. A number of herbal formulas were tested, but Ayush-82 and D-400 were most often studied. Thirty-five of the studies included came from the Western literature, 27 from the Indian. Seven were randomized controlled trials (RCTs) and 10 controlled clinical trials (CCTs) or natural experiments. Twenty-two studies went on to further analysis based on a set of criteria. Of these, 10 were RCTs, CCTs, or natural experiments, 12 were case series or cohort studies. There is evidence to suggest that the herbs C indica, holy basil, fenugreek, and G sylvestre, and the herbal formulas Ayush-82 and D-400 have a glucose-lowering effect and deserve further study. Evidence of effectiveness of several other herbs is less extensive (C tamala, E jambolana, and Momordica charantia). Conclusions There is heterogeneity in the available literature on Ayurvedic treatment for diabetes. Most studies test herbal therapy. Heterogeneity exists in the herbs and formulas tested (more than 44 different interventions identified) and in the method of their preparation. Despite these limitations, there are sufficient data for several herbs or herbal formulas to warrant further studies. C1 RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90407 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM shekelle@rand.org NR 34 TC 7 Z9 8 U1 0 U2 0 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD OCT PY 2005 VL 54 IS 10 BP 876 EP + PG 11 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 976CV UT WOS:000232711300012 PM 16202376 ER PT J AU Kaphingst, KA Rudd, RE Dejong, W Daltroy, LH AF Kaphingst, KA Rudd, RE Dejong, W Daltroy, LH TI Comprehension of information in three direct-to-consumer television prescription drug advertisements among adults with limited literacy SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article AB Direct-to-consumer (DTC) television advertisements present a number of facts about prescription drug risks and benefits in a brief time. This study assessed comprehension of information in three advertisements among 50 adults with limited literacy. Participants correctly answered an average of 59% of comprehension questions. The percentage of respondents correctly answering individual comprehension questions ranged from 26% to 92%. A multivariate analysis suggested that type of information ( risk vs. other) and channel ( text vs. audio) predicted comprehension. There was a significant interaction effect for literacy and place of birth. Our results suggest key areas for future research on comprehension of DTC advertising. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. Brigham & Womens Hosp, RBB Arthrit Res Ctr, Boston, MA 02115 USA. RP Kaphingst, KA (reprint author), NHGRI, Social & Behav Res Branch, Bldg 2,Room 4E30,2 Ctr Dr,MSC 0249, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU NIAMS NIH HHS [P60AR47782] NR 21 TC 22 Z9 22 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD OCT-NOV PY 2005 VL 10 IS 7 BP 609 EP 619 DI 10.1080/10810730500267647 PG 11 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 981VA UT WOS:000233114900003 PM 16278198 ER PT J AU Guerra, CE Dominguez, F Shea, JA AF Guerra, CE Dominguez, F Shea, JA TI Literacy and knowledge, attitudes, and behavior about colorectal cancer screening SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 01-05, 2002 CL ATLANTA, GA SP Soc Gen Internal Med ID FECAL-OCCULT-BLOOD; HEALTH LITERACY; OLDER WOMEN; SIGMOIDOSCOPY; MAMMOGRAPHY; MORTALITY; RECOMMENDATIONS; PARTICIPATION; ORGANIZATION; PREVENTION AB This cross-sectional survey explored the association between functional health literacy and knowledge of, beliefs and attitudes about, and reported usage of colorectal cancer screening tests. The results indicate that functional health literacy, as assessed by the Short Test of Functional Health Literacy in Adults (STOFHLA), is not an independent predictor of colorectal cancer screening knowledge, beliefs, attitudes, or behavior. Latino ethnicity and education, however, often predicted screening responses, suggesting that efforts to improve communication about colorectal cancer screening with Latino patients and patients with low education clearly are needed to reduce the disparities in awareness and utilization of colorectal cancer screening tests. This study also explored influences on intended screening behavior. Physician recommendation was found to be a powerful motivator of intention to undergo colorectal cancer screening regardless of literacy level, indicating that interventions aimed at increasing physician recommendation of colorectal cancer screening may be an effective way of increasing screening rates. C1 Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. USA, Dwight D Eisenhower Med Ctr, Dept Med, Ft Gordon, GA USA. Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Guerra, CE (reprint author), Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, 1221 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM carmen.guerra@uphs.upenn.edu FU AHRQ HHS [R01 HS10299] NR 33 TC 49 Z9 49 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD OCT-NOV PY 2005 VL 10 IS 7 BP 651 EP 663 DI 10.1080/10810730500267720 PG 13 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 981VA UT WOS:000233114900006 PM 16278201 ER PT J AU Yan, D Ouyang, XM Zhu, XF Du, LL Chen, ZY Liu, XZ AF Yan, D Ouyang, XM Zhu, XF Du, LL Chen, ZY Liu, XZ TI Refinement of the DFNA41 locus and candidate genes analysis SO JOURNAL OF HUMAN GENETICS LA English DT Article DE autosomal dominant; non-syndromic hearing loss; single nucleotide polymorphism; linkage and association analysis ID PEDIGREE DISEQUILIBRIUM TEST; LINKAGE-DISEQUILIBRIUM; HUMAN GENOME; REGION; DEAFNESS; MAPS AB We previously mapped the 41(rst) gene locus (DFNA41) for autosomal dominant hearing loss on chromosome 12q24-qter in a large multi-generational Chinese family. We determined that DFNA41 is located in a 15 cM region, proximal to the marker D12S1609. A maximum two point LOD score of 6.56 at theta = 0.0 was obtained with marker D12S343. In the current study, screening of eight candidate genes within the DFNA41 interval did not reveal the mutation causing deafness in this family. Eight highly informative single nucleotide polymorphisms ( SNPs) in the region of D12S343 were selected for linkage and association study. Because the pedigree studied here is a large family with many founders, we applied the transmission/disequilibrium (TDT) test. To account for the dependence of small families and the relatively small sample size, simulations were performed to obtain P-values. For three nearby SNPs spanning a 7 kb interval, we found significant evidence of linkage and association. The highest Z score of linkage and association of 3.6 ( P <= 0.0001) was obtained for SNP rs1566667. Haplotype analysis revealed that affected individuals were heterozygous for one core SNP (rs1027560 - rs1027557 - rs1566667 - rs1463865 - rs2078105) CAGTC haplotype, confirming location and autosomal dominant inheritance of the DFNA41 locus. Examination of pairwise LD calculation identified a major haplotype block defined by the four most centromeric SNPs. This study represents a significant refinement of the DFNA41 locus and should facilitate positional cloning of the disease gene. C1 Univ Miami, Dept Otolaryngol D48, Miami, FL 33136 USA. Loyola Univ, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. RP Liu, XZ (reprint author), Univ Miami, Dept Otolaryngol D48, 1666 NW 12th Ave, Miami, FL 33136 USA. EM xliu@med.miami.edu FU NIDCD NIH HHS [DC 05575] NR 20 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1435-232X J9 J HUM GENET JI J. Hum. Genet. PD OCT PY 2005 VL 50 IS 10 BP 516 EP 522 DI 10.1007/s10038-005-0286-0 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 980AR UT WOS:000232986800003 PM 16195816 ER PT J AU Jaff, MR AF Jaff, MR TI Conclusions SO JOURNAL OF HYPERTENSION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Vasc Diagnost Lab, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Room 5938,55 Fruit St, Boston, MA 02114 USA. EM docmrjaff@aol.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD OCT PY 2005 VL 23 SU 3 BP S31 EP S33 DI 10.1097/01.hjh.0000192099.29044.d4 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 001SN UT WOS:000234556700005 PM 16251846 ER PT J AU Jaff, MR AF Jaff, MR TI Special Issue: Diagnosis and management of renal artery stenosis - Introduction SO JOURNAL OF HYPERTENSION LA English DT Editorial Material ID HYPERTENSIVE PATIENTS; DISEASE; ANGIOPLASTY; THERAPY; FAILURE C1 Massachusetts Gen Hosp, Vasc Diagnost Lab, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr Outpatient Care, Room 5938,55 Fruit St, Boston, MA 02114 USA. EM docmrjaff@aol.com NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD OCT PY 2005 VL 23 SU 3 BP S1 EP S3 DI 10.1097/01.hjh.0000192095.06173.df PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 001SN UT WOS:000234556700001 PM 16251843 ER PT J AU Woodberry, T Suscovich, TJ Henry, LM August, M Waring, MT Kaur, A Hess, C Kutok, JL Aster, JC Wang, F Scadden, DT Brander, C AF Woodberry, T Suscovich, TJ Henry, LM August, M Waring, MT Kaur, A Hess, C Kutok, JL Aster, JC Wang, F Scadden, DT Brander, C TI alpha(E)beta(7) (CD103) expression identifies a highly active, tonsil-resident effector-memory CTL population SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR EXPRESSION; EPITHELIAL-CELLS; E-CADHERIN; INTEGRIN ALPHA(E)(CD103)BETA(7); PREFERENTIAL LOCALIZATION; INTESTINAL LYMPHOCYTES; LYMPHOID-TISSUE; LEEP-CAM AB The characterization of antiviral CTL responses has largely been limited to assessing Ag-specific immune responses in the peripheral blood. Consequently, there is an incomplete understanding of the cellular immune responses at mucosal sites where many viruses enter and initially replicate and how the Ag specificity and activation status of CTL derived from these mucosal sites may differ from that of blood-derived CTL. In this study, we show that EBV-specific CTL responses in the tonsils are of comparable specificity and breadth but of a significantly higher magnitude compared with responses in the peripheral blood. EBV-specific, tonsil-resident, but not PBMC-derived, T cells expressed the integrin/activation marker CD103 (alpha(E)beta(7)), consistent with the detection of its ligand, E-cadherin, on tonsillar squamous cells. These CD8-positive, CD103-positive, tonsil-derived CTL were largely CCR7- and CD45RA- negative effector-memory cells and responded to lower Ag concentrations in in vitro assays than their CD103-negative PBMC-derived counterparts. Thus, EBV-specific CTL in the tonsil, a crucial site for EBV entry and replication, are of greater magnitude and phenotypically distinct from CTL in the peripheral blood and may be important for effective control of this orally transmitted virus. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Univ Basel Hosp, CH-4031 Basel, Switzerland. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Labs, Boston, MA 02115 USA. RP Brander, C (reprint author), Partners AIDS Res Ctr, 5th Floor,MGH E,5214,149 13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org FU NIDCR NIH HHS [P01 DE01438-01] NR 57 TC 31 Z9 31 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2005 VL 175 IS 7 BP 4355 EP 4362 PG 8 WC Immunology SC Immunology GA 967LL UT WOS:000232092600026 PM 16177076 ER PT J AU Chren, MM AF Chren, MM TI Measurement of vital signs for skin diseases SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID QUALITY-OF-LIFE; DERMATOLOGY C1 Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Serv Dermatol, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. RP Chren, MM (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. FU NIAMS NIH HHS [K02 AR 02203-01] NR 12 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2005 VL 125 IS 4 BP VIII EP IX DI 10.1111/j.0022-202X.2005.23796.x PG 2 WC Dermatology SC Dermatology GA 973XU UT WOS:000232556700001 PM 16185256 ER PT J AU Liu, YT D'Arceuil, H He, JL Duggan, M Seri, S Hashiguchi, Y Nakatani, A Gonzalez, RG Pryor, J de Crespigny, A AF Liu, YT D'Arceuil, H He, JL Duggan, M Seri, S Hashiguchi, Y Nakatani, A Gonzalez, RG Pryor, J de Crespigny, A TI Dynamic susceptibility contrast perfusion imaging of cerebral ischemia in nonhuman primates: Comparison of Gd-DTPA and NMS60 SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI contrast media; gadolinium; stroke; cerebral ischemia; perfusion-weighted imaging ID HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; ACUTE STROKE; MR; DIFFUSION; AGENTS AB Purpose: To study a new gadolinium (Gd) contrast agent-NMS60-for MR perfusion-weighted imaging (PWI) of brain tissue. Materials and Methods: NMS60 is a Gd3+ trimer with a molecular weight of 2158 Daltons, and a T-2 relaxivity almost three times higher than that of Gd-DTPA. Middle cerebral artery (MCA) occlusion was induced in nine nonhuman primates. The animals were scanned acutely and for up to six follow-up time points. PWI peak, and time-to-peak maps were generated, and perfusion deficit volumes were measured from these maps. The values of peak, time-to-peak, and perfusion deficit volume were compared between NMS60 and GD-DTPA. Results: These results demonstrate that there was no significant difference in our calculated perfusion parameters between the two contrast agents. Conclusion: The two agents were found to be equally effective for PWI for acute and chronic stroke in primates. Along with its previously demonstrated advantage for T-1-enhanced imaging, the current results show that NMS60 is a viable contrast agent for use in stroke patients. C1 Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Comparat Med, Charlestown, MA USA. Nihon Medi Phys Co Ltd, Clin Dev Dept, Tokyo, Japan. Nihon Medi Phys Co Ltd, Res Ctr, Chiba, Japan. Massachusetts Gen Hosp, Dept Neurosurg, Endovasc Neuroradiiol Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Intervent Neuroradiol Sect, Boston, MA 02114 USA. RP de Crespigny, A (reprint author), Martinos Ctr, Dept Radiol, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM alexdec@nmr.mgh.harvard FU NINDS NIH HHS [1R01-NS41285] NR 19 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2005 VL 22 IS 4 BP 461 EP 466 DI 10.1002/jmri.20403 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 970NU UT WOS:000232317700003 PM 16142700 ER PT J AU Tesco, G Ginestroni, A Hiltunen, M Kim, M Dolios, G Hyman, BT Wang, R Berezovska, O Tanzi, RE AF Tesco, G Ginestroni, A Hiltunen, M Kim, M Dolios, G Hyman, BT Wang, R Berezovska, O Tanzi, RE TI APP substitutions V715F and L720P alter PS1 conformation and differentially affect A beta and AICD generation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amyloid-beta-peptide; amyloid precursor protein; amyloid precursor protein intracellular domain; non-steroidal anti-inflammatory drugs; presenilin 1; gamma-secretase ID AMYLOID PRECURSOR PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GAMMA-SECRETASE COMPLEX; ALZHEIMERS-DISEASE; INTRAMEMBRANE CLEAVAGE; TRANSMEMBRANE DOMAIN; PRESENILIN-1 MUTATIONS; INTRACELLULAR DOMAIN; NOTCH; SITE AB The 37-43 amino acid A beta peptide is the principal component of beta-amyloid deposits in Alzheimer's disease (AD) brain, and is derived by serial proteolysis of the amyloid precursor protein (APP) by beta- and gamma-secretase. gamma-Secretase also cleaves APP at Val50 in the A beta numbering (epsilon cleavage), resulting in the release of a fragment called APP intracellular domain (AICD). The aim of this study was to determine whether amino acid substitutions in the APP transmembrane domain differentially affect A beta and AICD generation. We found that the APPV715F substitution, which has been previously shown to dramatically decrease A beta(40) and A beta(42) while increasing A beta(38) levels, does not affect in vitro generation of AICD. Furthermore, we found that the APPL720P substitution, which has been previously shown to prevent in vitro generation of AICD, completely prevents A beta generation. Using a fluorescence resonance energy transfer (FRET) method, we next found that both the APPV715F and APPL720P substitutions significantly increase the distance between the N- and C-terminus of presenilin 1 (PS1), which has been proposed to contain the catalytic site of gamma-secretase. In conclusion, both APPV715F and APPL720P change PS1 conformation with differential effects on A beta and AICD production. C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. Massachusetts Gen Hosp, Alzheimers Res Unit, Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114 16th St C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Wang, Rong/A-8721-2009 FU NIA NIH HHS [5P01AG15379, P01 AG10491]; NIMH NIH HHS [1K12MH069281-01] NR 43 TC 25 Z9 26 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2005 VL 95 IS 2 BP 446 EP 456 DI 10.1111/j.1471-4159.2005.03381.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 968DU UT WOS:000232142900015 PM 16086682 ER PT J AU Jenkins, BG Andreassen, OA Dedeoglu, A Leavitt, B Hayden, M Borchelt, D Ross, CA Ferrante, RJ Beal, MF AF Jenkins, BG Andreassen, OA Dedeoglu, A Leavitt, B Hayden, M Borchelt, D Ross, CA Ferrante, RJ Beal, MF TI Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Huntington's disease; magnetic resonance spectroscopy; N-acetyl aspartate; neuronal area; transgenic mice ID INTRANUCLEAR INCLUSIONS; IN-VIVO; NEUROLOGICAL PHENOTYPE; TRINUCLEOTIDE REPEATS; NEUROCHEMICAL PROFILE; H-1-NMR SPECTROSCOPY; N-ACETYLASPARTATE; CELLULAR TOXICITY; GENE-EXPRESSION; H-1 MRS AB Huntington's disease is a neurodegenerative illness caused by expansion of CAG repeats at the N-terminal end of the protein huntingtin. We examined longitudinal changes in brain metabolite levels using in vivo magnetic resonance spectroscopy in five different mouse models. There was a large (> 50%) exponential decrease in N-acetyl aspartate (NAA) with time in both striatum and cortex in mice with 150 CAG repeats (R6/2 strain). There was a linear decrease restricted to striatum in N171-82Q mice with 82 CAG repeats. Both the exponential and linear decreases of NAA were paralleled in time by decreases in neuronal area measured histologically. Yeast artificial chromosome transgenic mice with 72 CAG repeats, but low expression levels, had less striatal NAA loss than the N171-82Q mice (15% vs. 43%). We evaluated the effect of gene context in mice with an approximate 146 CAG repeat on the hypoxanthine phosphoribosyltransferase gene (HPRT). HPRT mice developed an obese phenotype in contrast to weight loss in the R6/2 and N171-82Q mice. These mice showed a small striatal NAA loss (21%), and a possible increase in brain lipids detectable by magnetic resonance (MR) spectroscopy and decreased brain water T1. Our results indicate profound metabolic defects that are strongly affected by CAG repeat length, as well as gene expression levels and protein context. C1 Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Bedford VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol Pathol & Psychiat, Boston, MA USA. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC, Canada. Johns Hopkins Univ, Dept Neurol, Baltimore, MD USA. Johns Hopkins Univ, Dept Psychiat & Neurosci, Baltimore, MD USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. EM bgj@nmr.mgh.harvard.edu RI Ross, Christopher/H-8395-2013; Hayden, Michael/D-8581-2011; OI Hayden, Michael/0000-0001-5159-1419; Dedeoglu, Alpaslan/0000-0003-1156-0874; Andreassen, Ole A./0000-0002-4461-3568 FU NINDS NIH HHS [R01 5R01 NS39258-04] NR 40 TC 42 Z9 42 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2005 VL 95 IS 2 BP 553 EP 562 DI 10.1111/j.1471-4159.2005.03411.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 968DU UT WOS:000232142900025 PM 16135087 ER PT J AU Zhang, YP Da, RR Hilgenberg, LG Tourtellotte, WW Sobel, RA Smith, MA Olek, M Nagra, R Sudhir, G van den Noort, S Qin, YF AF Zhang, YP Da, RR Hilgenberg, LG Tourtellotte, WW Sobel, RA Smith, MA Olek, M Nagra, R Sudhir, G van den Noort, S Qin, YF TI Clonal expansion of IgA-positive plasma cells and axon-reactive antibodies in MS lesions SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE IgA and IgG plasma cells; clonal expansion; axonal reactive antibody in lesion; multiple sclerosis ID CENTRAL-NERVOUS-SYSTEM; IMMUNOGLOBULIN-CONTAINING CELLS; MULTIPLE-SCLEROSIS LESIONS; MYELIN BASIC-PROTEIN; CEREBROSPINAL-FLUID; SOMATIC MUTATION; DNA-POLYMERASE; B-CELLS; BRAIN; MATURATION AB Immunoglobulin A (IgA), the predominant immunoglobulin class in mucosal secretions, has been found in the cerebrospinal fluid of patients with multiple sclerosis (MS). In this study we examined the infiltration of clonally expanded IgA plasma cells in lesions of MS brains. Sequences of complementarity-determining region 3 of IgA variable heavy chain (V-H) genes demonstrated the clonal expansion of IgA-bearing plasma cells in MS lesions. Somatic mutations and ongoing intra-clonal mutations occurred in their V-H genes. Immunohistochemical study demonstrated infiltration of dimer and polymer IgAl- and A2-positive plasma cells in perivascular spaces, in the parenchyma of MS lesions, and in the adjacent white matter. Double immunofluorescence staining showed binding of IgA antibody on axons and walls of microvessels in the areas of chronic active and inactive demyelination. Bielshowsky's silver impregnation revealed axonal damage in these areas. These findings suggest that IgA in the CNS are localized on axons in lesions and may contribute to axonal damage in MS. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA. VA Greater Los Angeles Healthcare Syst, Serv Neurol, Los Angeles, CA USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. RP Qin, YF (reprint author), Univ Calif Irvine, Dept Neurol, 100 Irvine Hall, Irvine, CA 92697 USA. EM qiny@uci.edu FU NINDS NIH HHS [R01 NS40534-01A1, NS 046414] NR 43 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT PY 2005 VL 167 IS 1-2 BP 120 EP 130 DI 10.1016/j.jneuroim.2005.05.006 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 970XA UT WOS:000232344500014 PM 16099056 ER PT J AU Hodges, A Strand, AD Aragaki, AK Sengstag, T Hughes, G Elliston, LA Hartog, C Goldstein, DR Thu, D Hollingsworth, ZR Collin, F Synek, B Holmans, PA Young, AB Wexler, NS Delorenzi, M Kooperberg, C Augood, SJ Faull, RLM Olson, JM Luthi-Carter, R Jones, L AF Hodges, A Strand, AD Aragaki, AK Sengstag, T Hughes, G Elliston, LA Hartog, C Goldstein, DR Thu, D Hollingsworth, ZR Collin, F Synek, B Holmans, PA Young, AB Wexler, NS Delorenzi, M Kooperberg, C Augood, SJ Faull, RLM Olson, JM Luthi-Carter, R Jones, L TI Regional specificity of transcriptional changes in early grade Huntington's disease brain SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT World Congress on Huntingtons Disease CY SEP 10-13, 2005 CL Manchester, ENGLAND C1 Cardiff Univ, Dept Psychol Med, Cardiff, S Glam, Wales. Cardiff Univ, Dept Med Genet, Cardiff, S Glam, Wales. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Swiss Inst Expt Canc Res, NCCR Mol Oncol, CH-1066 Epalinges, Switzerland. SIB, Epalinges, Switzerland. Ecole Polytech Fed Lausanne, Lausanne, Switzerland. Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. Auckland City Hosp, Auckland, New Zealand. Columbia Univ, New York, NY 10027 USA. RI Holmans, Peter/F-4518-2015 OI Holmans, Peter/0000-0003-0870-9412 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2005 VL 76 SU 4 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 984PG UT WOS:000233316200005 ER PT J AU Kosinski, CM Schlangen, C Bellhaus, B Landwehrmeyer, GB Lindenberg, KS AF Kosinski, CM Schlangen, C Bellhaus, B Landwehrmeyer, GB Lindenberg, KS TI Myopathy as the first sign of Huntington's disease in a marathon man SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT World Congress on Huntingtons Disease CY SEP 10-13, 2005 CL Manchester, ENGLAND C1 Univ Hosp RWTH Aachen, Dept Neurol, Aachen, Germany. Univ Hosp RWTH Aachen, Dept Neuropathol, Aachen, Germany. Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2005 VL 76 SU 4 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 984PG UT WOS:000233316200080 ER PT J AU Lloret, A Seong, IS Srinidhi, J Gillis, T Hakky, M Kishikawa, S Gusella, J Wheeler, V MacDonald, M AF Lloret, A Seong, IS Srinidhi, J Gillis, T Hakky, M Kishikawa, S Gusella, J Wheeler, V MacDonald, M TI Modifiers of the Huntington's disease mutation in the mouse SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT World Congress on Huntingtons Disease CY SEP 10-13, 2005 CL Manchester, ENGLAND C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2005 VL 76 SU 4 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 984PG UT WOS:000233316200009 ER PT J AU Murck, H Manku, M Puri, BK Leavitt, BR Hayden, MR Ross, CA Rosenblatt, A Greenamyre, JT Hersch, S Vaddadi, KS AF Murck, H Manku, M Puri, BK Leavitt, BR Hayden, MR Ross, CA Rosenblatt, A Greenamyre, JT Hersch, S Vaddadi, KS TI Ethyl-EPA in Huntington's disease: A double blind, randomised, placebo controlled trial SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT World Congress on Huntingtons Disease CY SEP 10-13, 2005 CL Manchester, ENGLAND C1 Hammersmith Hosp, Imperial Coll, MRI Unit, MRC Clin Sci Ctr, London, England. Amarin Neurosci Ltd, Stirling, Scotland. Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC, Canada. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore Huntingtons Dis Ctr, Baltimore, MD 21205 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Monash Med Ctr, Dept Psychol Med, Clayton, Vic 3168, Australia. RI Hayden, Michael/D-8581-2011; Leavitt, Blair/G-1934-2012; Ross, Christopher/H-8395-2013 OI Hayden, Michael/0000-0001-5159-1419; NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2005 VL 76 SU 4 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 984PG UT WOS:000233316200034 ER PT J AU Curry, WT Cosgrove, GR Hochberg, FH Loeffler, J Zervas, NT AF Curry, WT Cosgrove, GR Hochberg, FH Loeffler, J Zervas, NT TI Stereotactic interstitial radiosurgery for cerebral metastases SO JOURNAL OF NEUROSURGERY LA English DT Article DE radiosurgery; cerebral metastasis; stereotactic; brain tumor; brachytherapy ID SINGLE BRAIN METASTASIS; RADIATION-THERAPY; RANDOMIZED-TRIAL; DEVICE; RADIOTHERAPY; TUMORS; IRRADIATION; EXPERIENCE; DOSIMETRY AB Object. The Photon Radiosurgery System (PRS) is a miniature x-ray generator that can stereotactically irradiate intracranial tumors by using low-energy photons. Treatment with the PRS typically occurs in conjunction with stereotactic biopsy, thereby providing diagnosis and treatment in one procedure. The authors review the treatment of patients with brain metastases with the aid of the PRS and discuss the indications, advantages, and limitations of this technique. Methods. Clinical characteristics, treatment parameters, neuroimaging-confirmed outcome, and survival were reviewed in all patients with histologically verified brain metastases who were treated with the PRS at the Massachusetts General Hospital between December 1992 and November 2000. Local control of lesions was defined as either stabilization or diminution in the size of the treated tumor as confirmed by Gd-enhanced magnetic resonance imaging. Between December 1992 and November 2000, 72 intracranial metastatic lesions in 60 patients were treated with the PRS. Primary tumors included lung (33 patients), melanoma (15 patients), renal cell (five patients), breast (two patients), esophageal (two patients), colon (one patient), and Merkle cell (one patient) cancers, and malignant fibrous histiocytoma (one patient). Supratentorial metastases were distributed throughout the cerebrum, with only one cerebellar metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated with a minimal peripheral dose of 16 Gy (range 10-20 Gy). At the last follow-up examination (median 6 months), local disease control had been achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that the survival rates at 6 and 12 months were 63 and 34%, respectively. Patients with a single brain metastasis survived a mean of I I months. Complications included four patients with postoperative seizures, three with symptomatic cerebral edema, two with hemorrhagic events, and three with symptomatic radiation necrosis requiring surgery. Conclusions. Stereotactic interstitial radiosurgery performed using the PRS can obtain local control of cerebral metastases at rates that are comparable to those achieved through open resection and external stereotactic radiosurgery. The major advantage of using the PRS is that effective treatment can be accomplished at the time of stereotactic biopsy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 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 Radiat Oncol, Boston, MA 02114 USA. RP Curry, WT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 55 Fruit St-Y93, Boston, MA 02114 USA. EM wcurry@partners.org NR 17 TC 16 Z9 16 U1 1 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 2005 VL 103 IS 4 BP 630 EP 635 DI 10.3171/jns.2005.103.4.0630 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 971LG UT WOS:000232385000009 PM 16266044 ER PT J AU Wallis, RA Panizzon, KL AF Wallis, RA Panizzon, KL TI Modulation of the mitochondrial ATP-sensitive potassium channel by cromakalim provides protection against CA1 neuronal injury induced by hypoxia and oxidative stress SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 23rd Annual National-Neurotrauma-Society Symposium CY NOV 10-11, 2005 CL Washington, DC SP Natl Neurotrauma Soc C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2005 VL 22 IS 10 MA P20 BP 1168 EP 1168 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 977ZS UT WOS:000232842600032 ER PT J AU You, Z Yager, P Takahashi, K Stahl, G Ezekowitz, A Whalen, M AF You, Z Yager, P Takahashi, K Stahl, G Ezekowitz, A Whalen, M TI Complement components independent of the membrane attack complex mediate tissue damage after controlled cortical impact in mice. SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 23rd Annual National-Neurotrauma-Society Symposium CY NOV 10-11, 2005 CL Washington, DC SP Natl Neurotrauma Soc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2005 VL 22 IS 10 MA P162 BP 1204 EP 1204 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 977ZS UT WOS:000232842600174 ER PT J AU You, Z Whalen, M AF You, Z Whalen, M TI Traumatic brain injury in mice deficient in tumor necrosis factor receptor-2 and FAS: Effects on histopathology and functional outcome SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 23rd Annual National-Neurotrauma-Society Symposium CY NOV 10-11, 2005 CL Washington, DC SP Natl Neurotrauma Soc C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2005 VL 22 IS 10 MA P253 BP 1227 EP 1227 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 977ZS UT WOS:000232842600264 ER PT J AU Yager, P Takahashi, K Ezekowitz, A Stahl, G You, Z Whalen, M AF Yager, P Takahashi, K Ezekowitz, A Stahl, G You, Z Whalen, M TI Traumatic brain injury in mice deficient in mannose binding lectins: Effects on histopathologic and functional outcome SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 23rd Annual National-Neurotrauma-Society Symposium CY NOV 10-11, 2005 CL Washington, DC SP Natl Neurotrauma Soc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2005 VL 22 IS 10 MA p342 BP 1250 EP 1250 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 977ZS UT WOS:000232842600354 ER PT J AU Sales, AE Sharp, ND Li, YF Greiner, GT Lowy, E Mitchell, P Sochalski, JA Cournoyer, P AF Sales, AE Sharp, ND Li, YF Greiner, GT Lowy, E Mitchell, P Sochalski, JA Cournoyer, P TI Nurse staffing and patient outcomes in veterans affairs hospitals SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PRACTICE ENVIRONMENT; HEALTH-CARE; WORK INDEX; MORTALITY AB Objective: To assess characteristics and perceptions of nurses working in the Veterans Health Administration (VHA), comparing types of nursing personnel, to benchmark to prior studies across healthcare systems. Background: Prior studies have shown relationships between positive registered nurse (RN) perceptions of the practice environment and patient outcomes. To date, no study has reported the comparison of RN perceptions of the practice environment in hospital nursing with those of non-RN nursing personnel. This study is the first to offer a more comprehensive look at perceptions of practice environment from the full range of the nursing work force and may shed light on issues such as the relationship of skill mix to nurse and patient outcomes. Methods: Cross-sectional observational study with a mailed survey administered to all nursing personnel in 125 VA Medical Centers between February and June 2003. Results: Compared with other types of nursing personnel in the VHA, RNs are generally less positive about their practice environments. However, compared with RNs in other countries and particularly with other RNs in the United States (Pennsylvania), VHA RNs are generally more positive about their practice environment and express more job satisfaction. Conclusions: The nursing work force of the VHA has some unique characteristics. The practice environment for nurses in the VHA is relatively positive, and may indicate that the VHA, as a system, provides an environment that is more like magnet hospitals. This is significant for a public sector hospital system. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Sales, AE (reprint author), VA Puget Sound Hlth Care Syst, HSR&D 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM ann.sales@med.va.gov RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 22 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD OCT PY 2005 VL 35 IS 10 BP 459 EP 466 DI 10.1097/00005110-200510000-00007 PG 8 WC Nursing SC Nursing GA 974EH UT WOS:000232573600007 PM 16220059 ER PT J AU Davis, BA Kiesel, CK McFarland, J Collard, A Coston, K Keeton, A AF Davis, BA Kiesel, CK McFarland, J Collard, A Coston, K Keeton, A TI Evaluating for quality instruments testing convergent validity of the consumer emergency care satisfaction scale SO JOURNAL OF NURSING CARE QUALITY LA English DT Article DE emergency department; patient satisfaction; quality; validity ID PATIENT SATISFACTION AB Having reliable and valid instruments is a necessity for nurses and others measuring concepts such as patient satisfaction. The purpose of this article is to describe the use of convergence to test the construct validity of the Davis Consumer Emergency Care Satisfaction Scale (CECSS). Results indicate, convergence of the CECSS with the Risser Patient Satisfaction Scale and 2 single-item visual analogue scales, therefore supporting construct validity. Persons measuring patient satisfaction with nurse behaviors in the emergency department can confidently use the CECSS. C1 Univ So Indiana, Coll Nursing & Hlth Profess, Evansville, IN 47712 USA. Deaconess Med Ctr, Emergency Dept, Evansville, IN USA. Morgan Cty Hosp & Med Ctr, Martinsville, IN USA. Floyd Mem Hosp, Urgent Care Ctr, New Albany, IN USA. Capital Reg Med Ctr, Tallahassee, FL USA. Englewood Community Hosp, Tallahassee, FL USA. RP Davis, BA (reprint author), Univ So Indiana, Coll Nursing & Hlth Profess, 8600 Univ Blvd, Evansville, IN 47712 USA. EM BDavis@usi.edu NR 11 TC 13 Z9 15 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1057-3631 J9 J NURS CARE QUAL JI J. Nurs. Care Qual. PD OCT-DEC PY 2005 VL 20 IS 4 BP 364 EP 368 PG 5 WC Nursing SC Nursing GA 967KB UT WOS:000232089000012 PM 16177589 ER PT J AU Fonteyn, M AF Fonteyn, M TI The interrelationships among thinking skills, research knowledge, and evidence-based practice SO JOURNAL OF NURSING EDUCATION LA English DT Editorial Material C1 Dana Farber Canc Inst, Phyliss F Cantor Ctr Res Nursing, Boston, MA 02115 USA. Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. RP Fonteyn, M (reprint author), Dana Farber Canc Inst, Phyliss F Cantor Ctr Res Nursing, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2005 VL 44 IS 10 BP 439 EP 439 PG 1 WC Nursing SC Nursing GA 972PZ UT WOS:000232467000001 PM 16268037 ER PT J AU Best, RG Stapleton, LM Downey, RG AF Best, Richard G. Stapleton, Laura M. Downey, Ronald G. TI Core self-evaluations and job burnout: The test of alternative models SO JOURNAL OF OCCUPATIONAL HEALTH PSYCHOLOGY LA English DT Article DE burnout; core self-evaluations; job satisfaction; perceived organizational constraints ID SATISFACTION; PERFORMANCE; EFFICACY; PERSONALITY; DIRECTIONS; STRESS AB Research on job burnout has traditionally focused on contextual antecedent conditions, although a theoretically appropriate conception implicates person-environment relationships. The authors tested several models featuring various combinations of personal and contextual influences on burnout and job satisfaction. Measures of core self-evaluations, organizational constraints, burnout, and job satisfaction were collected from 859 health care employees. Results from structural equations modeling analyses revealed an influence of core self-evaluations and perceived organizational constraints on job burnout and satisfaction, suggesting personal and contextual contributions. These results favor a broadening of current thinking about the impact of situational constraints on the expression of job burnout, as well as for the role of disposition for affective responding to effectively address occupational health problems. C1 Univ Texas Hlth Sci Ctr, S Texas Vet Hlth Syst, Dept Gen Med, VERDICT Field Program, San Antonio, TX 78229 USA. [Stapleton, Laura M.] Univ Texas Austin, Dept Educ Psychol, Austin, TX USA. [Downey, Ronald G.] Kansas State Univ, Dept Psychol, Manhattan, KS 66506 USA. RP Best, RG (reprint author), Univ Texas Hlth Sci Ctr, S Texas Vet Hlth Syst, Dept Gen Med, VERDICT Field Program, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM rbest@verdict.uthscsa.edu RI Stapleton, Laura/A-2357-2016 OI Stapleton, Laura/0000-0003-2383-772X NR 39 TC 76 Z9 83 U1 4 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1076-8998 J9 J OCCUP HEALTH PSYCH JI J. Occup. Health Psychol. PD OCT PY 2005 VL 10 IS 4 BP 441 EP 451 DI 10.1037/1076-8998.10.4.441 PG 11 WC Public, Environmental & Occupational Health; Psychology, Applied SC Public, Environmental & Occupational Health; Psychology GA V43VT UT WOS:000202963300011 PM 16248691 ER PT J AU Troulis, MJ Ward, BB Zuniga, JA AF Troulis, MJ Ward, BB Zuniga, JA TI Emerging technologies: Findings of the 2005 AAOMS Research Summit SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID VERTICAL RAMUS OSTEOTOMY; FOLATE RECEPTOR; ANIMAL-MODEL; NECK-CANCER; RECONSTRUCTION; HEAD C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ N Carolina, Dept Oral & Maxillofacial Surg, Chapel Hill, NC USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM mtroulis@partners.org OI zuniga, john/0000-0002-8602-2811 NR 23 TC 4 Z9 5 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2005 VL 63 IS 10 BP 1436 EP 1442 DI 10.1016/j.joms.2005.08.001 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 970FF UT WOS:000232289900006 PM 16182910 ER PT J AU Tholouli, E Divizio, D O'Connell, F Twomey, D Loda, M Golub, T Levenson, R Hoyland, J Yin, JAL Byers, R AF Tholouli, E Divizio, D O'Connell, F Twomey, D Loda, M Golub, T Levenson, R Hoyland, J Yin, JAL Byers, R TI Quantum dot based in situ hybridisation for gene expression profiling SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract CT 3rd Joint Meeting of the British Division of the International-Academy-of-Pahtology/Meeting of the Pathological-Society-of-Great-Britian-and-Ireland CY JUL 05-08, 2005 CL Univ Newcastle upon Tyne, Med Sch, Newcastle upon Tyne, ENGLAND SP Newcastle upon Tyne Hosp NHS Trust HO Univ Newcastle upon Tyne, Med Sch C1 Manchester Royal Infirm, Univ Dept Haematol, Manchester M13 9WL, Lancs, England. Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Broad Inst, Boston, MA USA. CRI, Boston, MA USA. Univ Manchester, Div Lab & Regenerat Med, Manchester, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 2005 VL 207 SU S BP 54 EP 54 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 971HZ UT WOS:000232376100217 ER PT J AU Young, RH AF Young, RH TI Perplexing patterns, perspicacious pathologists: Reflections on the diversity of gonadal neoplasms and those who have described them SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract CT 3rd Joint Meeting of the British Division of the International-Academy-of-Pahtology/Meeting of the Pathological-Society-of-Great-Britian-and-Ireland CY JUL 05-08, 2005 CL Univ Newcastle upon Tyne, Med Sch, Newcastle upon Tyne, ENGLAND SP Newcastle upon Tyne Hosp NHS Trust HO Univ Newcastle upon Tyne, Med Sch C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 2005 VL 207 SU S BP 61 EP 61 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 971HZ UT WOS:000232376100241 ER PT J AU Connors, PM Ulles, MM AF Connors, PM Ulles, MM TI The physical, psychological, and social implications of caring for the pregnant patient and newborn with cystic fibrosis SO JOURNAL OF PERINATAL & NEONATAL NURSING LA English DT Article DE counseling; cystic fibrosis; newborn; pregnancy; respiratory ID MECONIUM ILEUS; WOMEN; MALNUTRITION; CHILDREN; GROWTH; IMPACT AB Cystic fibrosis (CF) involves the exocrine glands and epithelial tissues of the pancreas, sweat glands, and mucus glands in the respiratory, digestive, and reproductive tracts. Significant pulmonary disease, poor nutritional status, and pulmonary hypertension are results of chronic infections. When the woman with CF becomes pregnant, her body may find it difficult to adjust to the normal physiological changes of pregnancy, with the pulmonary, cardiovascular, and nutritional status being particularly stressed. Both the mother and the fetus are at a significant risk for increased morbidity and mortality. The woman whose life and pregnancy are compromised by CF and/or the newborn who is diagnosed with CF offer the nurse an extremely challenging situation-one in which physical and psychological care are proportional in importance. As part of the healthcare team, which includes a perinatologist, a pulmonary medicine specialist, a neonatologist, an anesthesiologist, a geneticist, a dietitian, a respiratory therapist, a social worker, an ethicist, and perhaps a clergyman, the nurse helps to coordinate and carry out the care needed for a successful outcome. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Connors, PM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM pconnors1@partners.org NR 57 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0893-2190 J9 J PERINAT NEONAT NUR JI J. Perinat. Neonatal Nurs. PD OCT-DEC PY 2005 VL 19 IS 4 BP 301 EP 315 PG 15 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 985RE UT WOS:000233395000006 PM 16292132 ER PT J AU Wolfe, F Michaud, K Choi, HK Williams, R AF Wolfe, F Michaud, K Choi, HK Williams, R TI Household income and earnings losses among 6,396 persons with rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; indirect costs; productivity; household income; earnings ID HEALTH-ASSESSMENT QUESTIONNAIRE; WILLINGNESS-TO-PAY; CHRONIC DISEASE; INDIRECT COSTS; MEDICAL COSTS; SURVEY SF-36; OSTEOARTHRITIS; WORK; RELIABILITY; THERAPY AB Objective. Rheumatoid arthritis (RA) causes disability and reduced productivity. There are no large quantitative studies of earnings and productivity losses in patients with clinical RA, and no studies of household income losses. We describe methods for obtaining earnings and household income losses that are applicable to working as well as nonworking RA patients, and we perform such studies using these methods. Methods. We estimated cross-sectional expected annual earnings and household income losses in 6,649 persons with RA from Current Populations Survey (CPS) and O*NET (Occupational Information Network) data, and we estimated expected household income and earnings losses based on demographic characteristics after adjustment to Medical Outcomes Study Short-Form 36 (SF-36) population norms (internal method). Workplace productivity was measured by the Work Limitations Questionnaire (WLQ). Results. 27.9% of patients aged :5 65 years considered themselves disabled after 14.6 years of RA, and 8.8% received disability benefits. Annual earnings losses ranged between $2,319 and $3,407 by the CPS and internal method (preferred), with losses of 9.3% and 10.9%. A 0.25 difference in Health Assessment Questionnaire (HAQ) score was associated with a $1,095 difference in annual earnings. Productivity losses were 6% based on work limitations identified by the WLQ. Household income loss (percentage loss) including transfer payments was $6,287 (11.8%) for all patients, $4,247 (6.9%) for employed patients, and $7,374 (14.8%) for nonworking patients. Among nonworking nondisabled patients aged <= 65 years, income loss was 14.1 %. Conclusion. As measured by annual household income loss, the overall impact of RA is $6,287 (11.8%). Earnings and household income are dependent on functional status, education, age, ethnicity, and marital status. Income loss is predicted by the HAQ, HAQ-11, Modified HAQ, and SF-36. C1 Univ Kansas, Sch Med, Natl Data Bank Rheumat Dis, Arthrit Res Ctr Fdn, Wichita, KS 67214 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Rheumatol Unit, Boston, MA 02115 USA. Bristol Myers Squibb Co, Outcomes Res, Princeton, NJ 08543 USA. RP Wolfe, F (reprint author), Univ Kansas, Sch Med, Natl Data Bank Rheumat Dis, Arthrit Res Ctr Fdn, 1035 N Emporia,Suite 230, Wichita, KS 67214 USA. EM fwolfe@arthritis-research.org NR 38 TC 60 Z9 65 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2005 VL 32 IS 10 BP 1875 EP 1883 PG 9 WC Rheumatology SC Rheumatology GA 971KV UT WOS:000232383800008 PM 16206340 ER PT J AU Du, Y Pullman-Mooar, S Schumacher, HR AF Du, Y Pullman-Mooar, S Schumacher, HR TI Synovial sarcoma of the foot mimicking acute gouty arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE synovial sarcoma; acute gouty arthritis ID SYT AB Synovial sarcoma is a slow-growing soft tissue sarcoma that mainly affects young adults. Patients commonly present with a slowly enlarging mass in the paraarticular regions of extremities. We describe a case of synovial sarcoma with an unusually acute presentation near the first metatarsophalangeal joint that resembled acute gouty arthritis. C1 Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Rheumatol Sect, Philadelphia, PA USA. RP Schumacher, HR (reprint author), Hosp Univ Penn, Div Rheumatol, 5 Maloney,Suite 504,3400 Spruce St, Philadelphia, PA 19104 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2005 VL 32 IS 10 BP 2006 EP 2008 PG 3 WC Rheumatology SC Rheumatology GA 971KV UT WOS:000232383800027 PM 16206359 ER PT J AU Schoenfeld, DA Borenstein, M AF Schoenfeld, DA Borenstein, M TI Calculating the power or sample size for the logistic and proportional hazards models SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE sample size; power; logistic model; proportional hazards model; generalized linear models; multivariate normal integrals; Wald test ID REGRESSION; TESTS AB An algorithm is presented for calculating the power for the logistic and proportional hazards models in which some of the covariates are discrete and the remainders are multivariate normal. The mean and covariance matrix of the multivariate normal covariates may depend on the discrete covariates. The algorithm, which finds the power of the Wald test, uses the result that the information matrix can be calculated using univariate numerical integration even when there are several continuous covariates. The algorithm is checked using simulation and in certain situations gives more accurate results than current methods which are based on simple formulae. The algorithm is used to explore properties of these models, in particular, the power gain from a prognostic covariate in the analysis of a clinical trial or observational study. The methods can be extended to determine power for other generalized linear models. C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Biostat Programming Assoc Inc, Englewood, NJ 07631 USA. RP Schoenfeld, DA (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St, Boston, MA 02114 USA. EM dschoenfeld@partners.org NR 16 TC 13 Z9 13 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PD OCT PY 2005 VL 75 IS 10 BP 771 EP 785 DI 10.1080/00949650410001729445 PG 15 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 982CA UT WOS:000233134300001 ER PT J AU Kepka, L Suit, HD Goldberg, SI Rosenberg, AE Gebhardt, MC Hornicek, FJ DeLaney, TF AF Kepka, L Suit, HD Goldberg, SI Rosenberg, AE Gebhardt, MC Hornicek, FJ DeLaney, TF TI Results of radiation therapy performed after unplanned surgery (without re-excision) for soft tissue sarcomas SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE soft tissue sarcoma; radiation therapy; unplanned excision; re-excision; radiotherapy complications; local control ID LOCAL RECURRENCE; EXTREMITY SARCOMAS; PROGNOSTIC FACTORS; RESIDUAL DISEASE; RESECTION; RADIOTHERAPY; MARGINS; MANAGEMENT AB Background and Purpose: For soft tissue sarcomas (STS), some patients undergo an "unplanned surgery," non-oncologic resection for presumed benign tumor. The treatment of choice, in such cases, is re-excision combined (if indicated) with radiation. However, there are clinical situations when treatment by radiation alone is recommended. Here results of such an approach are assessed. Materials and Methods: Seventy-eight patients irradiated after unplanned surgery between 1970 and 1997 were identified from the MGH institutional database. Surgical margins were inevaluable in 50 (64%) and 28 (36%) had positive margins. Tumor characteristics: location, lower extremity (63%), upper extremity (27%), other (10%); median tumor size, 5 cm; grade-G1 (19%), G2 (49%), G3 (32%); AJCC stage (2002)-I (19%), II (54%), III (27%). Median radiation dose given was 66 Gy (range: 51-88). Results: With a median follow-up of 10 years, estimated local control rate was 88% and 86% at 5 and 10 years, respectively. Distant control rate was 80% at 5 and 10 years. Depth in the relation to the fascia, tumor size, and AJCC stage significantly influenced local recurrence- and distant metastasis-free survival. Ten major radiotherapy complications occurred from 1 to 21 years after treatment. Conclusions: Despite convincing data about the necessity for re-excision after unplanned surgery for STS, these results demonstrate that radiation therapy alone can be an effective alternate for those patients in whom functional or medical considerations preclude further surgery. The risk for potential radiation therapy complications, however, must also be considered in the treatment decision. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Div Biostat & Biomath, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped & Orthoped Oncol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Orthoped, Boston, MA 02215 USA. M Sklodowska Curie Mem Canc Ctr, Dept Radiat Oncol, Warsaw, Poland. Inst Oncol, Warsaw, Poland. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Div Biostat & Biomath, Boston, MA 02114 USA. EM tdelaney@partners.org NR 24 TC 22 Z9 24 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT 1 PY 2005 VL 92 IS 1 BP 39 EP 45 DI 10.1002/jso.20351 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 970OO UT WOS:000232319700008 PM 16180232 ER PT J AU Stelzner, M AF Stelzner, M TI Achieving balance in academic surgery SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Fundamentals of Surgical Research Course of the Association-for-Academic-Surgery CY NOV, 2004 CL Houston, TX SP Assoc Acad Surg DE balance; surgeon-scientist; family life; research ID INTESTINE; FALLS C1 Univ Washington, VAPSHCS Surg Serv 112, Dept Surg, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Stelzner, M (reprint author), Univ Washington, VAPSHCS Surg Serv 112, Dept Surg, 1660 S Columbian Way, Seattle, WA 98108 USA. EM stelzner@u.washington.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2005 VL 128 IS 2 SI SI BP 189 EP 193 DI 10.1016/j.jss.2005.09.005 PG 5 WC Surgery SC Surgery GA 979RS UT WOS:000232963100009 ER PT J AU Guinan, JJ Lin, T Cheng, HD AF Guinan, JJ Lin, T Cheng, HD TI Medial-olivocochlear-efferent inhibition of the first peak of auditory-nerve responses: Evidence for a new motion within the cochlea SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID GUINEA-PIG COCHLEA; BASILAR-MEMBRANE RESPONSES; OUTER HAIR-CELLS; SUPERIOR OLIVARY COMPLEX; FIBER RESPONSES; ELECTRICAL-STIMULATION; TUNING CURVES; MAMMALIAN COCHLEA; IMPULSE RESPONSES; FREQUENCY GLIDES AB Despite the insights obtained from click responses, the effects of medial-olivocochlear (MOC) efferents oil click responses from single-auditory-nerve (AN) fibers have not been reported. We recorded responses of cat single AN fibers to randomized click level series with and without electrical stimulation of MOC efferents.. MOC Stimulation inhibited (1) the whole response at low sound levels, (2) the decaying part of the response at all sound levels, and (3) the first peak of the response at moderate to high sound levels. The first two effects were expected from previous reports using tones and are consistent with it MOC-induced reduction of cochlear amplification. The inhibition of the AN first peak, which was strongest in the apex and middle of the cochlea, was unexpected because the first peak of the classic basilar-membrane (BM) traveling wave receives little or no amplification. In the cochlear base, the click data were ambiguous, but tone data showed particularly short group delays in the tail-frequency region that is strongly inhibited by MOC efferents. Overall, the data Support the hypothesis that there is a motion that bends inner-hair-cell stereocilia and can be inhibited by MOC efferents, a motion that is present through most, or all, of the cochlea and for which there is no counterpart in the classic BM traveling wave. (c) 2005 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Easton Peabody Lab Auditory Physiol, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Speech & Hearing Biosci & Technol Program, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Massachusetts Eye & Ear Infirm, Easton Peabody Lab Auditory Physiol, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC000235, R01-DC-00235] NR 79 TC 32 Z9 33 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2005 VL 118 IS 4 BP 2421 EP 2433 DI 10.1121/1.2017899 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 976DJ UT WOS:000232712700036 PM 16266164 ER PT J AU Wilens, T McBurnett, K Stein, M Lerner, M Spencer, T Wolraich, M AF Wilens, T McBurnett, K Stein, M Lerner, M Spencer, T Wolraich, M TI ADHD treatment with once-daily OROS methylphenidate: Final results from a long-term open-label study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; OROS MPH (CONCERTe); long-term study; safety ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; CLINICAL-PRACTICE GUIDELINE; HEALTH MULTIMODAL TREATMENT; FOLLOW-UP; HYPERACTIVE-CHILDREN; A-DAY; RELEASE METHYLPHENIDATE; CONTROLLED TRIAL; DOUBLE-BLIND; STIMULANTS AB Objective: Few studies have assessed effectiveness and tolerability of stimulants when used for prolonged periods in children with aftention-deficit/hyperactivity disorder (ADHD). This article presents final results from an open-label, multisite study of a once-daily formulation of methylphenidate (MPH), OROS (R) MPH. Method: Subjects received OROS MPH (18-54 mg initially, with adjustments based on clinical condition) for up to 24 months. Multiple measures of ADHD symptoms, vital signs, weight, height, and laboratory results were assessed throughout the study period. Results: A total of 407 children enrolled in the open-label study and 229 completed the trial. Effectiveness of OROS MPH therapy was maintained throughout the study as indicated by parent and investigator assessments. There was a 26% increase in mean daily dose over the study period, with the majority of the increase occurring during year 1. In general, treatment was well tolerated, with 31 (7.6%) of subjects discontinuing because of adverse events. Minimal effects on growth in height and weight were observed during the study. No clinically significant effects on vital signs or laboratory test parameters were observed. Conclusions: Sustained effectiveness of OROS MPH was maintained for up to 24 months with minimal effects on growth, tics, vital signs, or laboratory test values. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. RP Wilens, T (reprint author), Massachusetts Gen Hosp, YAW-6-6A,32 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org NR 28 TC 60 Z9 60 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2005 VL 44 IS 10 BP 1015 EP 1023 DI 10.1097/01.chi.0000173291.28688.e7 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 967GD UT WOS:000232078600012 PM 16175106 ER PT J AU Daoud, YJ Cervantes, R Foster, CS Ahmed, AR AF Daoud, YJ Cervantes, R Foster, CS Ahmed, AR TI Ocular pemphigus SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID VULGARIS AB Background: Ocular involvement in patients with pemphigus vulgaris (PV) has been rarely reported. We report ocular involvement in 11 patients with PV. Methods: Medical records of 11 biopsy-proven patients with PV treated during the period between 1990 and 2003 were reviewed and clinical information was analyzed. Results: Mean age at onset of PV was 52.3 years (range, 30-80 years). Ocular disease was preceded by involvement of the skin, other mucosae, or both in all patients. Ocular involvement was limited to the conjunctivae, the eyelids, or both. PV did not affect the visual acuity of any of the patients. Suprabasal acantholysis was observed on routine histologic examination of the conjunctiva and skin of the cyclic]. Direct immunofluorescence of perilesional eyelid skin demonstrated deposition of IgG on epithelial cell surface. Mean duration Of follow LIP Was 48.9 months (range, 4-100 months). Recurrence Of ocular disease occurred in 3 patients; recurrence at nonocular mucosae occurred in 4 patients. No sequelae were observed during detailed follow-up. Ocular pemphigus improved with systemic therapy. The mean remission period was 32 months (range, 0-92 months). Conclusions: Ocular involvement in PV is rare. Involvement is limited to the conjunctiva, the eyelids, or both. PV does not appear to affect visual acuity. Patients have full recovery without sequelae. C1 Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. New England Baptist Hosp, Dept Med, Ctr Blistering Dis, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med, 188 Longwood Ave, Boston, MA 02115 USA. EM Razzaque_Ahmed@hsdm.harvard.edu NR 12 TC 17 Z9 18 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 OCT PY 2005 VL 53 IS 4 BP 585 EP 590 DI 10.1016/j.jaad.2005.02.061 PG 6 WC Dermatology SC Dermatology GA 967BZ UT WOS:000232067800004 PM 16198777 ER PT J AU Avram, MM Avram, AS James, WD AF Avram, MM Avram, AS James, WD TI Subcutaneous fat in normal and diseased states - 1. Introduction SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATED RECEPTOR-GAMMA; WHITE ADIPOSE-TISSUE; FACTOR-ALPHA; INSULIN-RESISTANCE; ADIPOCYTE DIFFERENTIATION; PERIPHERAL LIPODYSTROPHY; PRIMARY CULTURES; GENE-EXPRESSION; ENERGY-BALANCE AB In recent years, our understanding of adipose tissue physiology and function has undergone an enormous transformation. Once considered a passive storage receptacle with a fixed number of cells and limited purpose, adipose tissue is now recognized as a complicated organ with important endocrine and metabolic functions. It is now known that both increased and decreased adipose tissue mass, as seen in obesity, anorexia, and lipodystrophy, have profound effects on multiple body systems, including immune, reproductive, and hematopoietic. The study of adipose tissue, therefore, is important not only for those who treat obesity, lipoatrophy, and their associated metabolic and endocrine derangements, but also for those dermatologists who specialize in the medical and surgical treatment of disorders within the body's largest adipose tissue subdivision, the subcutaneous fat. This introductory article is the first in a series about adipose tissue in normal and diseased states. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Avram, AS (reprint author), 905 5th Ave, New York, NY 10021 USA. EM asaderm@aol.com NR 92 TC 28 Z9 29 U1 0 U2 3 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 OCT PY 2005 VL 53 IS 4 BP 663 EP 670 DI 10.1016/j.jaad.2005.05.014 PG 8 WC Dermatology SC Dermatology GA 967BZ UT WOS:000232067800016 PM 16198790 ER PT J AU Avram, AS Avram, MM James, WD AF Avram, AS Avram, MM James, WD TI Subcutaneous fat in normal and diseased states - 2. Anatomy and physiology of white and brown adipose tissue SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID UNCOUPLING PROTEIN GENE; DIET-INDUCED THERMOGENESIS; ACTIVATED RECEPTOR-GAMMA; OBESE OBOB MOUSE; TOTAL-BODY FAT; MESSENGER-RNA; ADIPOCYTE DIFFERENTIATION; ENERGY-BALANCE; BETA(3)-ADRENERGIC RECEPTOR; BETA-3-ADRENERGIC RECEPTOR AB White and brown adipose tissues, both present to some degree in all mammals, represent counter actors in energy metabolism. One of the primary functions of white adipocytes is to store excess energy as lipid, which is then mobilized to other tissues in response to metabolic needs that arise in times of food shortage. White adipocyte physiology can be grouped into 3 main categories with potentially overlapping mechanisms: lipid metabolism, glucose metabolism, and endocrine functions. Brown adipocytes, on the other hand, use accumulated lipid from food primarily as a source for chemical energy that can then he released from the cell in the form of heat. Recently, new discoveries about the significance of brown fat have sparked interest in this organ as a potential tool in the fight against obesity in adult humans. A basic overview of the anatomy and physiology of adipose tissue, with particular emphasis on the differences between white and brown fat, is presented. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Avram, AS (reprint author), 905 5th Ave, New York, NY 10021 USA. EM asaderm@aol.com NR 147 TC 67 Z9 70 U1 0 U2 10 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 OCT PY 2005 VL 53 IS 4 BP 671 EP 683 DI 10.1016/j.jaad.2005.05.015 PG 13 WC Dermatology SC Dermatology GA 967BZ UT WOS:000232067800017 PM 16198791 ER PT J AU Min, LC Reuben, DB MacLean, CH Shekelle, PG Solomon, DH Higashi, T Chang, JT Roth, CP Kamberg, CJ Adams, J Young, RT Wenger, NS AF Min, LC Reuben, DB MacLean, CH Shekelle, PG Solomon, DH Higashi, T Chang, JT Roth, CP Kamberg, CJ Adams, J Young, RT Wenger, NS TI Predictors of overall quality of care provided to vulnerable older people SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality of care; care processes; quality indicators; aged; risk factors ID CORONARY-ARTERY-DISEASE; SEX-DIFFERENCES; COMPETING DEMANDS; MAMMOGRAPHY USE; UNITED-STATES; MANAGED CARE; HEALTH-CARE; WOMEN; COMMUNITY; PERFORMANCE AB OBJECTIVES: Prior research shows that the quality of care provided to vulnerable older persons is suboptimal, but little is known about the factors associated with care quality for this group. In this study, the influences of clinical conditions, types of care processes, and sociodemographic characteristics on the quality of care received by vulnerable older people were evaluated. DESIGN: Observational cohort study. SETTING: Two senior managed care plans. PARTICIPANTS: Three hundred sixty-two community-dwelling patients aged 65 and older identified as vulnerable by the Vulnerable Elder Survey (VES-13). MEASUREMENTS: Outcome variable: patients' observed-minus-expected overall quality score. Predictor variables: types of care processes, types and number of clinical conditions, sex, age, VES-13 score (composite score of function and self-rated health), income, education, mental health status, and number of quality indicators triggered. RESULTS: Patients whose conditions required more history-taking, counseling, and medication-prescribing care processes and patients with diabetes mellitus received lower-than-expected quality of care. A greater number of comorbid conditions was associated with higher-than-expected quality of care. Age, sex, VES-13 score, and other sociodemographic variables were not associated with quality of care. CONCLUSION: Complexity, vulnerability, and age do not predispose older persons to receive poorer-quality care. In contrast, older patients whose care requires time-consuming processes such as history taking and counseling are at risk for worse quality of care and should be a target for intervention to improve care. C1 Univ Calif Los Angeles, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Hlth Serv Res, Los Angeles, CA 90095 USA. RAND Corp, Santa Monica, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Min, LC (reprint author), Univ Calif Los Angeles, Dept Med, Div Geriatr, 10945 Conte Ave,Suite 2339,Box 951687, Los Angeles, CA 90095 USA. EM lmin@mednet.ucla.edu FU BHP HRSA HHS [PE-19001] NR 33 TC 38 Z9 38 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2005 VL 53 IS 10 BP 1705 EP 1711 DI 10.1111/j.1532-5415.2005.53520.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 966FR UT WOS:000232006000008 PM 16181169 ER PT J AU Parikh, CR Abraham, E Ancukiewicz, M Edelstein, CL AF Parikh, CR Abraham, E Ancukiewicz, M Edelstein, CL CA Acute Resp Distress Syndrome ARDS TI Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; RESPIRATORY-DISTRESS-SYNDROME; GELATINASE-ASSOCIATED LIPOCALIN; ACUTE TUBULAR-NECROSIS; ACUTE LUNG INJURY; PLASMA CYTOKINE; ORGAN FAILURE; BIOMARKER; SEPSIS; ARF AB Serum creatinine is not an ideal marker of renal function in patients with acute kidney injury (AKI). Previous studies demonstrated that urinary IL-18 is increased in human AKI. Thus, whether urine IL-18 is an early diagnostic marker of AKI was investigated. A nested case-control study was performed within the Acute Respiratory Distress Syndrome (ARDS) Network trial. AKI was defined as an increase in serum creatinine by at least 50% within the first 6 d of ARDS study enrollment. A total of 400 urine specimens that were collected on study days 0, 1, and 3 of the ARDS trial were available from 52 case patients and 86 control patients. The data were analyzed in a cross-sectional manner and according to the time before development of AKI. The median urine IL-18 levels were significantly different at 24 and 48 It before AKI in case patients as compared with control patients. On multivariable analysis, urine IL-18 values predicted development of AKI 24 and 48 It later after adjustment for demographics, sepsis, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) III score, serum creatinine, and urine output. Urine IL-18 levels of >100 pg/ml are associated with increased odds of AKI of 6.5 (95% confidence interval 2.1 to 20.4) in the next 24 h. On diagnostic performance testing, urine IL-18 demonstrates an area under the receiver operating characteristic curve of 73% to predict AKI in the next 24 h. The urine IL-18 values were also significantly different between survivors and nonsurvivors (P < 0.05), and on multivariable analysis, the urine IL-18 value on day 0 is an independent predictor of mortality. Urinary IL-18 levels can be used for the early diagnosis of AKI. Urine IL-18 levels also predict the mortality of patients who have ARDS and are in the intensive care unit. C1 Yale Univ, Sch Med, Nephrol Sect, New Haven, CT USA. Univ Colorado, Hlth Sci Ctr, Div Pulm & Crit Care, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Nephrol, Denver, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, Sch Med, 950 Campbell Ave,Box 151B, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu FU NHLBI NIH HHS [N01-HL46055, N01-HL46054, N01-HL46056, N01-HL46057, N01-HL46058, N01-HL46059, N01-HL46060, N01-HL46061, N01-HL46062, N01-HL46063, N01-HL46064]; NIDDK NIH HHS [K23-DK064689, R01-DK56851] NR 25 TC 280 Z9 317 U1 2 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2005 VL 16 IS 10 BP 3046 EP 3052 DI 10.1681/ASN.2005030236 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 968DH UT WOS:000232141600026 PM 16148039 ER PT J AU Blonder, LX Heilman, KM Ketterson, T Rosenbek, J Raymer, A Crosson, B Maher, L Glueckauf, R Roth, LG AF Blonder, LX Heilman, KM Ketterson, T Rosenbek, J Raymer, A Crosson, B Maher, L Glueckauf, R Roth, LG TI Affective facial and lexical expression in aprosodic versus aphasic stroke patients SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE emotion; language; nonverbal communication; cerebral infarction; laterality; facial expression ID BRAIN-DAMAGED PATIENTS; RIGHT-HEMISPHERE; EMOTIONAL EXPRESSION; PROSODY; LANGUAGE; PERCEPTION; COMMUNICATION; VALIDATION; DISEASE; SPEECH AB Past research has shown that lesions in the left cerebral hemisphere often result in aphasia, while lesions in the right hemisphere frequently impair the production of emotional prosody and facial expression. At least 3 processing deficits might account for these affective symptoms: (1) failure to understand the conditions that evoke emotional response; (2) inability to experience emotions; (3) disruption in the capacity to encode non-verbal signals. To better understand these disorders and their underlying mechanisms, we investigated spontaneous affective communication in right hemisphere damaged (RHD) stroke patients with aprosody and left hemisphere damaged (LHD) stroke patients with aphasia. Nine aprosodic RHD patients and 14 aphasic LHD patients participated in a videotaped interview within a larger treatment protocol. Two naive raters viewed segments of videotape and rated facial expressivity. Verbal affect production was tabulated using specialized software. Results indicated that RHD patients smiled and laughed significantly less than LHD patients. In contrast, RHD patients produced a greater percentage of emotion words relative to total words than did LHD patients. These findings suggest that impairments in emotional prosodic production and facial expressivity associated with RHD are not induced by affective- conceptual deficits or an inability to experience emotions. Rather, they likely represent channel-specific nonverbal encoding abnormalities. C1 Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Behav Sci, Lexington, KY 40536 USA. VA Med Ctr, BRRC, Gainesville, FL USA. Univ Florida, Dept Neurol, Gainesville, FL USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. Univ Florida, Dept Commun Disorders, Gainesville, FL USA. Old Dominion Univ, Norfolk, VA USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. Florida State Univ, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA. RP Blonder, LX (reprint author), Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. EM lxblond@email.uky.edu RI Crosson, Bruce/L-3128-2013 FU NIDCD NIH HHS [P50DC03888] NR 43 TC 20 Z9 21 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD OCT PY 2005 VL 11 IS 6 BP 677 EP 685 DI 10.1017/S13556177050794 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 980NQ UT WOS:000233025600003 PM 16248903 ER PT J AU Zhang, P Guccione, JM Nicholas, SI Walker, JC Crawford, PC Shamal, A Saloner, DA Wallace, AW Ratcliffe, MB AF Zhang, P Guccione, JM Nicholas, SI Walker, JC Crawford, PC Shamal, A Saloner, DA Wallace, AW Ratcliffe, MB TI Left ventricular volume and function after endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm in sheep SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID FINITE-ELEMENT MODEL; REDUCTION SURGERY; RESTORATION; EXTENSION; STIFFNESS AB Objective: Endoventricular patch plasty (the Dor procedure) has gained favor as a surgical treatment for heart failure associated with large anteroapical myocardial infarction. We tested the hypothesis that the Dor procedure reduces left ventricular volume, increases end-systolic elastance, decreases diastolic compliance, and maintains left ventricular function. Methods: In 6 male Dorsett sheep, the left anterior descending coronary artery and its second diagonal branch were ligated 40% of the distance from apex to base. Sixteen weeks after myocardial infarction, a Dor procedure was performed with a Dacron patch that was 50% of the infarct neck dimension. Absolute left ventricular volume was measured with magnetic resonance imaging, and left ventricular pressure and relative left ventricular volume changes during pharmacologic preload reduction were measured with a volume conductance catheter 2 weeks before and 2 and 6 weeks after the Dor procedure. End-systolic elastance, diastolic compliance, and Starling relationships were calculated from the resultant left ventricular pressure/volume loops. Results: Two weeks after the Dor procedure, the left ventricular volume at end systole and end diastole was significantly reduced, and there was no redilation at 6 weeks. Six weeks after the Dor procedure, the ejection fraction was significantly increased. Although stroke volume increased slightly at 6 weeks, the change was not significant. The slopes of end-systolic elastance, diastolic compliance, and Starling relationships were unchanged at 2 and 6 weeks. Conclusions: The Dor procedure significantly reduces left ventricular volume. Unlike linear repair, left ventricular volume changes seem stable. The ejection fraction is improved, and left ventricular function (stroke volume and the Starling relationship) is maintained. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, Div Surg Serv 112D, 4150 Clement St, San Francisco, CA 94121 USA. EM Mark.Ratcliffe@med.va.gov FU NHLBI NIH HHS [R01 HL063348, R01-HL-58759, R01-HL-63348] NR 24 TC 20 Z9 21 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 OCT PY 2005 VL 130 IS 4 BP 1032 EP 1038 DI 10.1016/j.jtcvs.2005.05.039 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 973SX UT WOS:000232544000013 PM 16214516 ER PT J AU Maree, AO Curtin, RJ Chubb, A Dolan, C Cox, D O'Brien, J Crean, P Shields, DC Fitzgerald, DJ AF Maree, AO Curtin, RJ Chubb, A Dolan, C Cox, D O'Brien, J Crean, P Shields, DC Fitzgerald, DJ TI Cyclooxygenase-1 haplotype modulates platelet response to aspirin SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE aspirin; cardiovascular disease; cyclooxygenase-1; genetics; platelets; thromboxane ID MYOCARDIAL-INFARCTION; SYNTHASE; DISEASE; STROKE; DEATH; RISK AB Background: Aspirin (acetylsalicylic acid) irreversibly inhibits platelet cyclooxygenase (COX)-1, the enzyme that converts arachidonic acid (AA) to the potent platelet agonist thromboxane (TX) A(2). Despite clear benefit from aspirin in patients with cardiovascular disease (CAD), evidence of heterogeneity in the way individuals respond has given rise to the concept of 'aspirin resistance.' Aims: To evaluate the hypothesis that incomplete suppression of platelet COX as a consequence of variation in the COX-I gene may affect aspirin response and thus contribute to aspirin resistance. Patients and methods: Aspirin response, determined by serum TXB2 levels and AA-induced platelet aggregation, was prospectively studied in patients (n = 144) with stable CAD taking aspirin (75-300 mg). Patients were genotyped for five single nucleotide polymorphisms in COX-1 [A-842G, C22T (R8W), G128A (Q41Q), C644A (G213G) and C714A (L237M)]. Haplotype frequencies and effect of haplotype on two platelet phenotypes were estimated by maximum likelihood. The four most common haplotypes were considered separately and less common haplotypes pooled. Results: COX-1 haplotype was significantly associated with aspirin response determined by AA-induced platelet aggregation (P = 0.004; 4 d.f.). Serum TXB2 generation was also related to genotype (P = 0.02; 4 d.f.). Conclusion: Genetic variability in COX-1 appears to modulate both AA-induced platelet aggregation and thromboxane generation. Heterogeneity in the way patients respond to aspirin may in part reflect variation in COX-I genotype. C1 Harvard Univ, Sch Med, Dept Vasc Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Coll Surg, Dept Clin Pharmacol, Dublin, Ireland. St James Hosp, Dept Cardiol, Dublin 8, Ireland. Beaumont Hosp, Dept Cardiol, Dublin 9, Ireland. RP Maree, AO (reprint author), Harvard Univ, Sch Med, Dept Vasc Med, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM amaree@partners.org RI Vangjeli, Ciara/B-4329-2010; Cox, Dermot/A-8465-2008 OI Cox, Dermot/0000-0003-1365-3396 NR 15 TC 140 Z9 154 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2005 VL 3 IS 10 BP 2340 EP 2345 DI 10.1111/j.1538-7836.2005.01555.x PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 972GV UT WOS:000232443200029 PM 16150050 ER PT J AU Schumm, JA Stines, LR Hobfoll, SE Jackson, AP AF Schumm, JA Stines, LR Hobfoll, SE Jackson, AP TI The double-barreled burden of child abuse and current stressful circumstances on adult women: The kindling effect of early traumatic experience SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID SEXUAL ABUSE; PTSD SYMPTOMS; RISK-FACTORS; RESOURCE LOSS; DEPRESSION; DISORDER; COMMUNITY; CONSERVATION; NEGLECT; FEMALE AB Child sexual abuse and child physical abuse were compared to assess how these experiences might both positively predict and sensitize women to the effects of current stress exposure, assessed in terms of psychosocial resource loss (e.g., personal and interpersonal resources). Resource loss was in turn, hypothesized to increase later depressive mood and posttraumatic stress disorder Severity. Participants were 176 low-income women (58% African American, 38% European American), interviewed twice over 6 months. Child sexual abuse predicted increases in resource loss, which then predicted posttraumatic stress disorder and depressive mood. Women who reported higher levels of child physical abuse were more negatively impacted by resource loss than those who reported lower child physical abuse. Results suggest that child abuse results in both greater stress exposure later and greater vulnerability to that exposure. C1 Boston Consortium Clin Psychol, Boston, MA USA. Kent State Univ, Kent, OH 44242 USA. Med Univ S Carolina, Dept Vet Affairs, Psychol Internship Program, Charleston, SC 29425 USA. Summa Hlth Syst, Kent, OH USA. RP Schumm, JA (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM Jererniah.Schumm@med.va.gov FU NIMH NIH HHS [5 R01 MH045669-12] NR 55 TC 19 Z9 19 U1 2 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2005 VL 18 IS 5 BP 467 EP 476 DI 10.1002/jts.20054 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 986JU UT WOS:000233446700010 PM 16281244 ER PT J AU Yalla, SV AF Yalla, SV TI Longitudinal changes in post-void residual and voided volume among community dwelling men - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material ID OBSTRUCTION C1 Harvard Univ, Sch Med, Dept Urol, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Yalla, SV (reprint author), Harvard Univ, Sch Med, Dept Urol, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2005 VL 174 IS 4 BP 1321 EP 1322 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 963UK UT WOS:000231831400043 ER PT J AU Zhu, M Maslow, J Mikota, SK Isaza, R Dunker, F Riddle, H Peloquin, CA AF Zhu, M Maslow, J Mikota, SK Isaza, R Dunker, F Riddle, H Peloquin, CA TI Population pharmacokinetics of pyrazinamide in elephants SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID BOVIS SUBSP CAPRAE; MYCOBACTERIUM-TUBERCULOSIS; MAXIMUS AB This study was undertaken to characterize the population pharmacokinetics (PK) therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20-30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0-24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with T-max at or before 2 h regardless of the method of drug administration. C-max at a mean dose of 25.6 (+/- 4.6) mg/kg was 19.6 (+/- 9.5 mu g/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 +/- 4.2 mg/kg, C-max was 25% (4.87 +/- 4.89 mu g/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 +/- 15.2 mg/kg yielded Cmax of 12.3 +/- 6.3 mu g/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher C-max and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between I and 2 h postdose. Higher doses may be required if the achieved C-max values are below the recommended 2050 mu g/mL range. C1 Vet Affairs Med Ctr, Infect Dis Sect, Philadelphia, PA 19104 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. Elephant Care Int, Waveland, MS USA. Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, Gainesville, FL 32610 USA. San Francisco Zool Gardens, San Francisco, CA USA. Riddle Elephant & Wildlife Sancutary, Greenbriar, AR USA. Univ Colorado, Sch Pharm, Denver, CO 80202 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. RP Maslow, J (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, 151 Univ & Woodlands Aves, Philadelphia, PA 19104 USA. EM joel.maslow@med.va.gov NR 19 TC 12 Z9 12 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2005 VL 28 IS 5 BP 403 EP 409 DI 10.1111/j.1365-2885.2005.00670.x PG 7 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 979YD UT WOS:000232980200001 PM 16207301 ER PT J AU Yang, XZ Kurteva, S Ren, XP Lee, S Sodroski, J AF Yang, XZ Kurteva, S Ren, XP Lee, S Sodroski, J TI Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Review ID MURINE LEUKEMIA-VIRUS; HEMAGGLUTININ SURFACE-DENSITY; MEMBRANE-FUSION PROTEIN; CELL-CELL FUSION; INFLUENZA HEMAGGLUTININ; RECEPTOR-BINDING; LOW PH; TRANSMEMBRANE GLYCOPROTEIN; ENDOPROTEOLYTIC CLEAVAGE; ANTIBODY NEUTRALIZATION AB The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs) function as a trimer, mediating virus entry by promoting the fusion of the viral and target cell membranes. HIV-1 Env trimers induce membrane fusion through a pH-independent pathway driven by the interaction between an Env trimer and its cellular receptors, CD4 and CCR5/CXCR4. We studied viruses with mixed heterotrimers of wild-type and dominant-negative Envs to determine the number (T) of Env trimers required for HIV-1 entry. To our surprise, we found that a single Env trimer is capable of supporting HIV-1 entry; i.e., T = 1. A similar approach was applied to investigate the entry stoichiometry of envelope glycoproteins from amphotropic murine leukemia virus (A-MLV), avian sarcoma/leukosis virus type A (ASLV-A), and influenza A virus. When pseudotyped on HIV-1 virions, the A-MLV and ASLV-A Envs also exhibit a T = 1 entry stoichiometry. In contrast, eight to nine influenza A virus hemagglutinin trimers function cooperatively to achieve membrane fusion and virus entry, using a pH-dependent pathway. The different entry requirements for cooperativity among Env trimers for retroviruses and influenza A virus may influence viral strategies for replication and evasion of the immune system. 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, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM xinzhen_yang@dfci.harvard.edu FU NIAID NIH HHS [AI24755, AI31783, AI46725, R01 AI031783, R37 AI024755, U01 AI046725] NR 128 TC 110 Z9 111 U1 1 U2 4 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 OCT PY 2005 VL 79 IS 19 BP 12132 EP 12147 DI 10.1128/JVI.79.19.12132-12147.2005 PG 16 WC Virology SC Virology GA 966AR UT WOS:000231992500002 PM 16160141 ER PT J AU Lu, R Vandegraaff, N Cherepanov, P Engelman, A AF Lu, R Vandegraaff, N Cherepanov, P Engelman, A TI Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replication SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; VIRAL-DNA BINDING; HIV-1 INTEGRASE; IN-VITRO; TERMINAL DOMAIN; COMPLEMENTATION ANALYSIS; NUCLEAR-LOCALIZATION; CRYSTAL-STRUCTURE; GENETIC ANALYSES; ZINC-BINDING AB Retroviral integrases (INs) function in the context of preintegration complexes (PICs). Two conserved Lys residues in the N-terminal domain of human immunodeficiency virus type 1 (HIV-1) IN were analyzed here for their roles in integration and virus replication. Whereas HIV-1(K46A) grew like the wild type, HIV-1(K34A) was dead. Yet recombinant INK34A protein functioned in in vitro integration assays, and Vpr-INK34A efficiently transcomplemented the infectivity defect of an IN active site mutant virus in cells. HIV-1(K34A) was therefore similar to a number of previously characterized mutant viruses that failed to replicate despite encoding catalytically competent IN. To directly analyze mutant PIC function, a sensitive PCR-based integration assay was developed. HIV-1(K34A) and related mutants failed to support detectable levels (< 1% of wild type) of integration. We therefore concluded that mutations like K34A disrupted higher-order interactions important for PIC function/maturation compared to the innate catalytic activity of IN enzyme. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu RI Cherepanov, Peter/F-6859-2010 OI Cherepanov, Peter/0000-0002-0634-538X FU NIAID NIH HHS [AI52014, AI39394, AI60354, P30 AI060354, R01 AI039394, R01 AI052014, R37 AI039394] NR 49 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2005 VL 79 IS 19 BP 12584 EP 12591 DI 10.1128/JVI.79.19.12584-12591.2005 PG 8 WC Virology SC Virology GA 966AR UT WOS:000231992500047 PM 16160186 ER PT J AU Tian, SM Choi, WT Liu, DX Pesavento, J Wang, YL An, J Sodroski, JG Huang, ZW AF Tian, SM Choi, WT Liu, DX Pesavento, J Wang, YL An, J Sodroski, JG Huang, ZW TI Distinct functional sites for human immunodeficiency virus type 1 and stromal cell-derived factor 1 alpha on CXCR4 transmembrane helical domains SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; SMALL-MOLECULE INHIBITOR; HIV-1 ENTRY; EXTRACELLULAR DOMAINS; CORECEPTOR ACTIVITY; IDENTIFICATION; RESIDUES; FUSION; ACTIVATION; COMPLEX AB The entry of human immunodeficiency virus type 1 (HIV-1) into the cell is initiated by the interaction of the viral surface envelope protein with two cell surface components of the target cell, CD4 and a chemokine coreceptor, usually CXCR4 or CCR5. The natural ligand of CXCR4 is stromal cell-derived factor 1 alpha (SDF-1 alpha). Whereas the overlap between HIV-1 and SDF-1 alpha functional sites on the extracellular domains of CXCR4 has been well documented, it has yet to be determined whether there are sites in the transmembrane (TM) helices of CXCR4 important for HIV-1 and/or SDF-1 alpha functions, and if such sites do exist, whether they are overlapping or distinctive for the separate functions of CXCR4. For this study, by employing alanine-scanning mutagenesis, I-125-SDF-1 alpha competition binding, Ca2+ mobilization, and cell-cell fusion assays, we found that the mutation of many CXCR4 TM residues, including Tyr(45), HiS(79), Asp(97), Pro(63), Trp(252), Tyr(255), ASP(262), Glu(288), His(294), and Asn(291), could selectively decrease HIV-1-mediated cell fusion but not the binding activity of SDF-1 alpha. Pbe(87) and Phe(292), which were involved in SDF-1 alpha binding, did not play a significant role in the coreceptor activity of CXCR4, further demonstrating the disconnection between physiological and pathological activities of CXCR4 TM domains. Our data also show that four mutations of the second extracellular loop, D182A, D187A, F189A, and P191A, could reduce HIV-1 entry without impairing either ligand binding or signaling. Taken together, our first detailed characterization of the different functional roles of CXCR4 TM domains may suggest a mechanistic basis for the discovery of new selective anti-HIV agents. C1 Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. Univ Illinois, Dept Chem, Urbana, IL 61801 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Raylight Chemokine Pharmaceut Inc, La Jolla, CA 92037 USA. RP Huang, ZW (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM ziweihuang@burnham.org FU NHLBI NIH HHS [HL16059]; NIGMS NIH HHS [GM57761, R01 GM057761] NR 34 TC 45 Z9 45 U1 1 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 OCT PY 2005 VL 79 IS 20 BP 12667 EP 12673 DI 10.1128/JVI.79.20.12667-12673.2005 PG 7 WC Virology SC Virology GA 969OI UT WOS:000232243200007 PM 16188969 ER PT J AU Allen, TM Yu, XG Kalife, ET Reyor, LL Lichterfeld, M John, M Cheng, M Allgaier, RL Mui, S Frahm, N Alter, G Brown, NV Johnston, MN Rosenberg, ES Mallal, SA Brander, C Walker, BD Altfeld, M AF Allen, TM Yu, XG Kalife, ET Reyor, LL Lichterfeld, M John, M Cheng, M Allgaier, RL Mui, S Frahm, N Alter, G Brown, NV Johnston, MN Rosenberg, ES Mallal, SA Brander, C Walker, BD Altfeld, M TI De novo generation of escape variant-specific CD8(+) T-cell responses following cytotoxic T-lymphocyte escape in chronic human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURALLY CONSTRAINED EPITOPE; ORIGINAL ANTIGENIC SIN; HIV-1 INFECTION; VIRAL ESCAPE; IMMUNE CONTROL; IN-VIVO; AIDS; RECOGNITION; MUTATIONS; LIGANDS AB Human immunodeficiency virus type I (HIV-1) evades CD8(+) T-cell responses through mutations within targeted epitopes, but little is known regarding its ability to generate de novo CD8(+) T-cell responses to such mutants. Here we examined gamma interferon-positive, HIV-1-specific CD8(+) T-cell responses and autologous viral sequences in an HIV-1-infected individual for more than 6 years following acute infection. Fourteen optimal HIV-1 T-cell epitopes were targeted by CD8(+) T cells, four of which underwent mutation associated with dramatic loss of the original CD8(+) response. However, following the G(357)S escape in the HLA-A11-restricted Gag(349-359) epitope and the decline of wild-type-specific CD8(+) T-cell responses, a novel CD8(+) T-cell response equal in magnitude to the original response was generated against the variant epitope. CD8(+) T cells targeting the variant epitope did not exhibit cross-reactivity against the mild-type epitope but rather utilized a distinct T-cell receptor V beta repertoire. Additional studies of chronically HIV-1-infected individuals expressing HLA-A11 demonstrated that the majority of the subjects targeted the G(357)S escape variant of the Gag(349-319) epitope, while the wild-type consensus sequence was significantly less frequently recognized. These data demonstrate that de novo responses against escape variants of CD8(+) T-cell epitopes can be generated in chronic HIV-1 infection and provide the rationale for developing vaccines to induce CD8(+) T-cell responses directed against both the wild-type and variant forms of CD8 epitopes to prevent the emergence of cytotoxic T-lymphocyte escape variants. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02129 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [R01 AI028568, AI054178, AI28568, AI50429, R01 AI050429, R01 AI054178, R37 AI028568, R56 AI054178, U01 AI052403, U01 AI52403] NR 48 TC 100 Z9 102 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2005 VL 79 IS 20 BP 12952 EP 12960 DI 10.1128/JVI.79.20.12952-12960.2005 PG 9 WC Virology SC Virology GA 969OI UT WOS:000232243200035 PM 16188997 ER PT J AU Lauer, GM Lucas, M Timm, J Ouchi, K Kim, AY Day, CL zur Wiesch, JS Paranhos-Baccala, G Sheridan, I Casson, DR Reiser, M Gandhi, RT Li, B Allen, TM Chung, RT Klenerman, P Walker, BD AF Lauer, GM Lucas, M Timm, J Ouchi, K Kim, AY Day, CL zur Wiesch, JS Paranhos-Baccala, G Sheridan, I Casson, DR Reiser, M Gandhi, RT Li, B Allen, TM Chung, RT Klenerman, P Walker, BD TI Full-breadth analysis of CD8(+) T-cell responses in acute hepatitis C virus infection and early therapy SO JOURNAL OF VIROLOGY LA English DT Article ID INTERFERON-ALPHA THERAPY; IMMUNE-RESPONSE; LYMPHOCYTE RESPONSES; VIRAL CLEARANCE; PLUS RIBAVIRIN; PEGINTERFERON; ESCAPE; SPECIFICITY; PERSISTENCE; KINETICS AB Multispecific CD8(+) T-cell responses are thought to be important for the control of acute hepatitis C virus (KCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8(+) T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8(+) T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8(+) T-cell responses, as well as CD4(+) T-cell responses. Rapid recrudescence also occurred despite broad CD8(+) T-cell responses. Importantly, in vivo suppression of CD3(+) T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8(+) T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 2JD, England. CNRS BioMerieux, F-69365 Lyon, France. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Med Univ Klin, Berufsgenossenschaftl Kliniken Bergmannsheil, D-44789 Bochum, Germany. RP Lauer, GM (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM glauer@helix.mgh.harvard.edu RI Yang, Chen/G-1379-2010; Day, Cheryl/J-9844-2012; Allen, Todd/F-5473-2011 FU NIAID NIH HHS [AI31563, R01 AI031563] NR 42 TC 83 Z9 86 U1 1 U2 2 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 OCT PY 2005 VL 79 IS 20 BP 12979 EP 12988 DI 10.1128/JVI.79.20.12979-12988.2005 PG 10 WC Virology SC Virology GA 969OI UT WOS:000232243200038 PM 16189000 ER PT J AU Ahmed, A Ness, J Howard, G Aronow, WS AF Ahmed, A Ness, J Howard, G Aronow, WS TI Cerebrovascular diseases as primary hospital discharge diagnoses: National trend (1970-2000) among older adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID STROKE INCIDENCE; UNITED-STATES; SURVIVAL; MORTALITY; 1ST-EVER; BLACKS AB Background. Cerebrovascular diseases are a common cause of mortality, morbidity, and hospitalization among older adults. However, the long-term national trends in cerebrovascular disease-related hospitalizations in this age group are not well known. Methods. We used the National Center for Health Statistics trend data from the National Hospital Discharge Surveys (1970-2000) to determine incidence of cerebrovascular disease-related hospitalizations among persons 65 years and older in the United States. Only patients discharged with a primary discharge diagnosis of cerebrovascular disease were included. We estimated rates of hospitalization per 1000 civilian residents 65 years and older, for all patients and stratified by age, sex, and race. Results. Among persons 65 years of age and older, the total number of cerebrovascular disease-related hospitalizations increased from 372,000 in 1970 to 711,000 in 2000. However, the rates of hospitalization due to cerebrovascular disease remained unchanged at 20.7/1000 in 1970 and 20.4/1000 in 2000. The rates for persons 75-84 years and > 85 years were, respectively, 2 and 3 times higher than that for persons 65-74 years throughout the study period. Rates for men and women were comparable and stable during the study period. Rates for African Americans, in contrast, increased from 14/1000 in 1970 to 20.6/1000 in 2000, peaking in 1985 (27.4/1000). Conclusions. The overall rates of hospitalization due to cerebrovascular disease remained high yet stable. However, the absolute number of hospitalizations due to cerebrovascular disease increased considerably, with potential for serious social, financial, and public health implications for the coming decades. C1 Univ Alabama, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Birmingham, AL USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Ctr Aging, Birmingham, AL 35294 USA. Univ Alabama, Geriatr Heart Failure Clin, Birmingham, AL USA. Birmingham VA Med Ctr, Sect Geriatr, Birmingham, AL USA. Birmingham VA Med Ctr, Geriatr Heart Failure Clin, Birmingham, AL USA. Alabama Qual Assurance Fdn, Heart Failure Project, Birmingham, AL USA. Univ Iowa Hlth Care, Div Gen Internal Med, Dept Internal Med, Iowa City, IA USA. Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. New York Med Coll, Dept Med, Sect Cardiol, Valhalla, NY 10595 USA. New York Med Coll, Dept Med, Sect Geriatr, Valhalla, NY 10595 USA. Mt Sinai Sch Med, New York, NY USA. RP Ness, J (reprint author), Univ Iowa Hosp & Clin, Dept Internal Med, Div Gen Internal Med, SE624,GH,200 Hawkins Dr, Iowa City, IA 52242 USA. EM jose-ness@uiowa.edu NR 21 TC 4 Z9 4 U1 0 U2 0 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 OCT PY 2005 VL 60 IS 10 BP 1328 EP 1332 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 985XN UT WOS:000233412100019 PM 16282569 ER PT J AU Feliers, D Chen, XY Akis, N Choudhury, GG Madaio, M Kasinath, BS AF Feliers, D Chen, XY Akis, N Choudhury, GG Madaio, M Kasinath, BS TI VEGF regulation of endothelial nitric oxide synthase in glomerular endothelial cells SO KIDNEY INTERNATIONAL LA English DT Article DE glomerular endothelial cells; VEGF; signal transduction; eNOS ID RENAL EPITHELIAL-CELLS; VASCULAR-PERMEABILITY FACTOR; GROWTH-FACTOR EXPRESSION; PROTEIN-SYNTHESIS; TYROSINE KINASE; ANGIOTENSIN-II; ANGIOGENESIS; PATHWAY; ACTIVATION; FLT-1 AB VEGF regulation of endothelial nitric oxide synthase in glomerular endothelial cells. Background. Vascular endothelial growth factor (VEGF) regulation of endothelial nitric oxide synthase (eNOS) and signaling pathways involved have not been well studied in glomerular endothelial cells (GENCs). Methods. GENCs grown from tsA58 Immortomice (R) were used. Immunoblotting and in-cell Western blot analysis were employed to assess changes in VEGF receptor signaling pathway and eNOS phosphorylation of ser1177. Immunokinase assay and immunoblotting with phosphospecific antibodies were performed to assess activity of kinases. Results. VEGF rapidly induced tyrosine phosphorylation of type 1 and type 2 VEGF receptors. Physical association between VEGF-receptor 2 (VEGF-R2) and insulin receptor substrate (IRS-1) and phosphatidylinositol 3'-kinase (PI3K) was induced by VEGF, which augmented PI3K activity in VEGF-R2 immunoprecipitates. VEGF stimulated Akt phosphorylation in a PI3K-dependent manner. VEGF increased eNOS phosphorylation on Ser1177. Activation of eNOS was associated with nitric oxide generation as measured by medium nitrite content. Signaling mechanisms involved in VEGF stimulation of eNOS were explored. VEGF-induced eNOS phosphorylation was abolished by SU1498, a VEGF-R2 inhibitor, LY294002, a PI3K inhibitor, and infection of cells with an adenovirus carrying a dominant negative-mutant of Akt, demonstrating the requirement of the VEGF-R2/IRS-1/PI3K/Akt axis for activation of eNOS. VEGF also activated extracellular signal-regulated protein kinase (ERK) in a time-dependent manner; and VEGF-stimulated eNOS phosphorylation on Ser1177 was prevented by PD098059, an upstream inhibitor of ERK, demonstrating that ERK was involved in VEGF regulation of eNOS. ERK phosphorylation was abolished by LY294002, suggesting ERK was downstream of PI3K in VEGF-treated GENC. Conclusions. Our data demonstrate that in GENC, VEGF stimulates VEGF-R2/IRS-1/PI3K/Akt axis to regulate eNOS phosphorylation on Ser1177 in conjunction with the ERK signaling pathway. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol,S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, OBrien Kidney Res Ctr, San Antonio, TX 78229 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol,S Texas Vet Healthcare Syst, 7703 Floyd Curl Dr,Mail Code 7882, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu RI Akis, Nese/A-5745-2017 OI Akis, Nese/0000-0002-8491-2685 FU NIDDK NIH HHS [DK55815, DK53088, T32 DK7006] NR 40 TC 40 Z9 40 U1 1 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2005 VL 68 IS 4 BP 1648 EP 1659 DI 10.1111/j.1523-1755.2005.00575.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 963JT UT WOS:000231801300030 PM 16164642 ER PT J AU Stringer, KD Komers, R Osman, SA Oyama, TT Lindsley, JN Anderson, S AF Stringer, KD Komers, R Osman, SA Oyama, TT Lindsley, JN Anderson, S TI Gender hormones and the progression of experimental polycystic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article DE gender; estrogen; polycystic kidney disease; VEGF; nitric oxide; endothelin ID RENIN-ANGIOTENSIN SYSTEM; RECEPTOR GENE-EXPRESSION; HAN-SPRD RATS; RENAL-DISEASE; GROWTH-FACTOR; REPLACEMENT THERAPY; FAMILY MEMBERS; SEX-HORMONES; NITRIC-OXIDE; ESTROGEN AB Background. Male gender is a risk factor for progression of autosomal-dominant polycystic kidney disease (ADPKD), clinically and in the Han:SPRD rat model. Orchiectomy limits progression, but mechanisms of the detrimental effect of androgen, and/or beneficial effects of estrogen, are not known. This protocol tested the hypothesis that male gender (intact androgen status) promotes progression, while female gender (intact estrogen status) is protective; and that these disease-modifying effects are due to changes in expression of known fibrotic mediators. Methods. Studies were performed in male and female noncystic control (+/+) and cystic (+/-) rats subjected to orchiectomy, ovariectomy, or sham operation. At 12 weeks of age, renal function was measured. Blood and kidneys were taken for measurement of plasma and renal renin, endothelin (ET-1), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF), using biochemical, protein expression, and immunohistochemical methods. Results. Cystic male rats exhibited significantly reduced glomerular filtration (GFR) and effective renal plasma flow (ERPF) rates, with suppression of plasma and renal renin, up-regulation of renal ET-1 and eNOS, and down-regulation of renal VEGF expression. Orchiectomy attenuated the fall in GFR and ERPF, while numerically limiting changes in eNOS and VEGF. Female rats exhibited less cystic growth, with normal renin status, lesser elevation of renal ET-1, and proportionately lesser changes in VEGF and eNOS. Ovariectomy led to higher blood pressure and reduced GFR and ERPF, with a trend toward upregulation of ET-1, and significant down-regulation of VEGF and eNOS. Conclusion. Female gender is protective, but ovariectomy attenuates the protective effect of female gender, in association with changes in renal expression of ET-1, VEGF, and eNOS. The accelerated disease in male rats can be attenuated by orchiectomy and consequent changes in expression of disease mediators. C1 Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. Inst Clin & Expt Med, Ctr Diabet, Prague, Czech Republic. Portland VA Med Ctr, Portland, OR USA. RP Anderson, S (reprint author), Oregon Hlth Sci Univ, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM anderssh@ohsu.edu NR 64 TC 30 Z9 32 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2005 VL 68 IS 4 BP 1729 EP 1739 DI 10.1111/j.1523-1755.2005.00589.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 963JT UT WOS:000231801300037 PM 16164649 ER PT J AU Park, SE DeFrate, LE Sugg, JF Gill, TJ Rubash, HE Li, GA AF Park, SE DeFrate, LE Sugg, JF Gill, TJ Rubash, HE Li, GA TI The change in length of the medial and lateral collateral ligaments during in vivo knee flexion SO KNEE LA English DT Article DE MCL; LCL; deep MCL; MRI; 3D modeling ID POSTERIOR CRUCIATE LIGAMENT; ANTERIOR CRUCIATE; SUPPORTING STRUCTURES; TENSION PATTERN; FLEXED KNEE; STRAIN; INJURY; INSTABILITY; STABILITY; VALGUS AB The collateral ligaments of the knee are important in maintaining knee stability. However, little data has been reported on the in vivo function of the collateral ligaments. The objective of this study was to investigate the change in length of different fiber bundles of the medial collateral ligament (MCL), deep fibers of the MCL (DMCL) and the lateral collateral ligament (LCL) during in vivo knee flexion. The knees of five healthy subjects were scanned using magnetic resonance imaging. These images were used to create three-dimensional models of the tibia and femur, including the insertions of the collateral ligaments. The MCL, DMCL, and LCL were each divided into three equal portions: an anterior bundle, a middle bundle and a posterior bundle. Next, the subjects were imaged from two orthogonal directions using fluoroscopy while performing a quasi-static lunge from 0 degrees to 90 degrees of flexion. The models and fluoroscopic images were then used to reproduce the in vivo motion of the knee. From these models, the length of each bundle of each ligament was measured as a function of flexion. The length of the anterior bundle of the MCL did not change significantly with flexion. The length of the posterior bundle of the MCL consistently decreased with flexion (p < 0.05). The changes in deformation of the DMCL and LCL as a function of flexion were similar to each other. The length of the anterior bundles increased with flexion and the length of the posterior bundles decreased with flexion. These data indicate that the collateral ligaments do not elongate uniformly as the knee is flexed, with different bundles becoming taut and slack. These data may help to provide a better understanding of the in vivo function of the collateral ligaments and be used to improve surgical reconstructions of the collateral ligaments. Furthermore, the data suggest that the different roles of various portions of the collateral ligaments along the flexion path should be considered before releasing the collateral ligaments during knee arthroplasty. (c) 2005 Elsevier B.V All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 34 TC 28 Z9 35 U1 4 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0968-0160 J9 KNEE JI Knee PD OCT PY 2005 VL 12 IS 5 BP 377 EP 382 DI 10.1016/j.knee.2004.12.011 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 968QW UT WOS:000232178200010 PM 16411288 ER PT J AU Tanaka, T Kojima, I Ohse, T Ingelfinger, JR Adler, S Fujita, T Nangaku, M AF Tanaka, T Kojima, I Ohse, T Ingelfinger, JR Adler, S Fujita, T Nangaku, M TI Cobalt promotes angiogenesis via hypoxia-inducible factor and protects tubulointerstitium in the remnant kidney model SO LABORATORY INVESTIGATION LA English DT Article DE hypoxia-inducible factor (HIF)-1; HIF-2; angiogenesis; cobalt; apoptosis ID ENDOTHELIAL GROWTH-FACTOR; CHRONIC-RENAL-FAILURE; TRANSCRIPTION FACTOR; TRANSGENIC MICE; THROMBOTIC MICROANGIOPATHY; HIF-1-ALPHA/VP16 HYBRID; RECEPTOR-2 FLK-1; GENE-EXPRESSION; TUBULAR CELLS; FACTOR VEGF AB Tubulointerstitial hypoxia has been implicated in a number of progressive renal diseases, and several lines of evidence indicate that the administration of angiogenic growth factors ameliorates tubulointerstitial injury. We hypothesized that induction of hypoxia-inducible factors (HIF) mediates renoprotection by their angiogenic properties. At 5 - 9 weeks after subtotal nephrectomy, cobalt was administered to rats to activate HIF. Histological evaluation demonstrated that the tubulointerstitial injury was significantly ameliorated in animals that received cobalt ( score: 2.51 +/- 0.12 ( cobalt) vs 3.21 +/- 0.24 ( vehicle), P<0.05). Furthermore, animals receiving cobalt had fewer vimentin- and TdT-mediated dUTP nick-end labeling ( TUNEL)- positive tubular cells. The renoprotective effect of cobalt was associated with the preservation of peritubular capillary networks ( rarefaction index: 13.7 +/- 0.4 ( cobalt) vs 18.6 +/- 0.9 ( vehicle), P<0.01). This improvement in capillary networks was accompanied by an increased number of proliferating (PCNA-positive) glomerular and peritubular endothelial cells. The angiogenesis produced by this method was not accompanied by an increase in vascular permeability. Furthermore, in vitro experiments clarified that HIF-1 in tubular epithelial cells promotes proliferation of endothelial cells and that HIF-2 overexpressed in renal endothelial cells mediates migration and network formation. Collectively, these findings demonstrate a renoprotective role of HIF through angiogenesis and provide a rationale for therapeutic approaches to target HIF for activation. C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 1130033, Japan. Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. New York Med Coll, Dept Med, Div Nephrol, Valhalla, NY 10595 USA. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM mnangaku-tky@umin.ac.jp RI Nangaku, Masaomi/A-5300-2010 NR 56 TC 103 Z9 112 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2005 VL 85 IS 10 BP 1292 EP 1307 DI 10.1038/labinvest.3700328 PG 16 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 968EX UT WOS:000232145800011 PM 16127428 ER PT J AU Kennedy, DW Kuhn, FA Hamilos, DL Zinreich, SJ Butler, D Warsi, G Pfister, PJ Tavakkol, A AF Kennedy, DW Kuhn, FA Hamilos, DL Zinreich, SJ Butler, D Warsi, G Pfister, PJ Tavakkol, A TI Treatment of chronic rhinosinusitis with high-dose oral terbinafine: A double blind, placebo-controlled study SO LARYNGOSCOPE LA English DT Article DE oral terbinafine; chronic rhinosinusitis; children; lacrimal ID ALLERGIC FUNGAL SINUSITIS; NASAL POLYPS; DIAGNOSIS AB Objectives: To evaluate antifungal terbinafine in patients with chronic rhinosinusitis. Study Design: Randomized, double-blind, placebo-controlled multicenter pilot study. Methods: Fifty-three adults with chronic rhinosinusitis received terbinafine 625 mg/day (n = 25) or placebo (n = 28) once daily for 6 weeks. Sinus secretions were collected at screening for mycology. Computed tomography was graded for extent of opacification at baseline and at week 6 using a modification of the Lund-Mackay scoring system. Patients recorded rhinosinusitis symptoms on a visual analogue scale and completed the Rhinosinusitis Disability Index. Results: Positive fungal cultures were found in 41 of 53 patients (17 terbinafine, 24 placebo). (Two subjects from the Terbinafine group and one subject from the control group had no week 6 data). The mean opacification scores pre- and posttreatment for the entire study group improved from 24.2 to 22.5 in placebo (n = 26) and from 26.3 to 24.2 in terbinafine group (n = 23). The least squares means for percent change from baseline (SE) were -6.0 (8.7) for placebo compared with -7.2 (8.1) for terbinafine; 95% confidence interval for treatment difference (-18.9, 21.1); P = .91. Results were similar when only patients with positive fungal cultures were evaluated in the efficacy analysis. Investigator therapeutic evaluations and sinus symptom scores were not significantly different between the two groups at baseline or at treatment completion. Conclusion: Treatment with terbinafine failed to improve the symptoms or radiographic appearance of chronic rhinosinusitis even when nasal irrigation samples were positive for fungus on culture. One consideration is that the fungi isolated were not a major pathologic factor in this cohort. It is also possible that, even at high dose, terbinafine may not have maintained therapeutic levels in the nasal secretions. C1 Univ Penn, Sch Med, Dept Otolaryngol, Philadelphia, PA 19104 USA. Georgia Nasal & Sinus Inst, Savannah, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Novartis Pharmat AG, Basel, Switzerland. RP Kennedy, DW (reprint author), Univ Penn, Sch Med, Dept Otolaryngol, Philadelphia, PA 19104 USA. EM kennedyd@uphs.upenn.edu NR 15 TC 67 Z9 70 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2005 VL 115 IS 10 BP 1793 EP 1799 DI 10.1097/01.mlg.0000175683.81260.26 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 976HS UT WOS:000232724800015 PM 16222197 ER PT J AU Kamegaya, Y Farinelli, WA Echague, AVV Akita, H Gallagher, J Flotte, TJ Anderson, RR Redmond, RW Kochevar, IE AF Kamegaya, Y Farinelli, WA Echague, AVV Akita, H Gallagher, J Flotte, TJ Anderson, RR Redmond, RW Kochevar, IE TI Evaluation of photochemical tissue bonding for closure of skin incisions and excisions SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE tissue repair; lasers; wound healing; skin; incision; excision; wound closure ID CORNEAL INCISIONS; TENSILE-STRENGTH; ROSE-BENGAL; LASER; KERATODESMOS; MODEL; ADHESIVES; DERMABOND; RABBITS; STITCH AB Background and Objectives: Photochemical tissue bonding (PTB) is a new non-thermal technique for tissue repair involving application of a photochemically active dye and irradiation with visible light. The objective was to compare PTB with standard sutures and the tissue adhesive, octyl cyanoacrylate, for closure of skin incisions and excisions. Study Design/Materials and Methods: Incisions and excisions made on the flanks of a Hanford mini-pig were secured with subcutaneous sutures. Superficial closure methods were 3-0 monofilament sutures, PTB (Rose Bengal and green light), tissue adhesive and the combination of tissue adhesive then PTB. Wounds were evaluated 2, 4, and 6 weeks postoperatively for cosmetic outcomes and histology. Results: Cosmetic outcomes and histological scar width of incisions and excisions did not differ among the treatment groups at 2, 4, and 6 weeks. Conclusion: PTB is as effective as standard sutures for wound closure in porcine skin in terms of cosmetic outcomes and safety. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, WEL-224, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu NR 32 TC 43 Z9 49 U1 1 U2 5 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 OCT PY 2005 VL 37 IS 4 BP 264 EP 270 DI 10.1002/lsm.20221 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 981PJ UT WOS:000233100200002 PM 16196042 ER PT J AU Bruno, B Giaccone, L Rotta, M Anderson, K Boccadoro, M AF Bruno, B Giaccone, L Rotta, M Anderson, K Boccadoro, M CA Multiple Myeloma Res Fdn TI Novel targeted drugs for the treatment of multiple myeloma: from bench to bedside SO LEUKEMIA LA English DT Review DE mutliple myeloma; new drugs; signaling pathways ID THALIDOMIDE PLUS DEXAMETHASONE; ENDOTHELIAL GROWTH-FACTOR; CELL-GROWTH; RECEIVING THALIDOMIDE; COMBINATION THERAPY; ANTITUMOR-ACTIVITY; SALVAGE THERAPY; FACTOR-I; SURVIVAL; PATHWAY AB Multiple myeloma remains an incurable plasma cell neoplasm. New insights into its pathogenesis have identified signaling pathways that have become potential therapeutic targets. It has clearly been established that intracellular regulatory proteins and interactions between malignant plasma cells and the bone marrow microenvironment play an important role in their survival and drug resistance. Several new agents associated with molecular targets are currently being investigated to design new treatment strategies aimed at prolonging survival and improving quality of life. This review illustrates their mechanisms of action and the possible future clinical applications. C1 Univ Turin, Div Ematol, Osped S Giovanni Battist, I-10126 Turin, Italy. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Bruno, B (reprint author), Univ Turin, Div Ematol, Osped S Giovanni Battist, Via Genova 3, I-10126 Turin, Italy. EM benedetto.bruno@unito.it NR 58 TC 40 Z9 42 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2005 VL 19 IS 10 BP 1729 EP 1738 DI 10.1038/sj.leu.2403905 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 968ZU UT WOS:000232204000003 PM 16094421 ER PT J AU Delmonico, FL Aufses, A Bozorgzadeh, A Delgado-Vega, D Distant, DA Dubler, NN Emre, S Feng, S Freeman, RB Fung, JJ Gordon, FD Hasz, RD Kinkhabwala, M Lake, JR Merion, RM Orlowski, J Pinson, CW Powell, T Sheiner, PA Teperman, L Williams, C Wong, HH Novelle, AC Osten, W Wickens, L Barhydt, N Doesschate, J Emrich, S Maynus, D McMurdo, L Valente, K AF Delmonico, FL Aufses, A Bozorgzadeh, A Delgado-Vega, D Distant, DA Dubler, NN Emre, S Feng, S Freeman, RB Fung, JJ Gordon, FD Hasz, RD Kinkhabwala, M Lake, JR Merion, RM Orlowski, J Pinson, CW Powell, T Sheiner, PA Teperman, L Williams, C Wong, HH Novelle, AC Osten, W Wickens, L Barhydt, N Doesschate, J Emrich, S Maynus, D McMurdo, L Valente, K CA New York State Dept Hlth Workgroup TI Workgroup on expanded criteria organs for liver transplantation SO LIVER TRANSPLANTATION LA English DT Article C1 New York City Dept Hlth, Troy, NY 12180 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Organ Bank Inc, Boston, MA USA. United Network Organ Sharing, New York, NY USA. Mt Sinai Med Ctr, Dept Hlth Policy, New York, NY 10029 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Latino Org Liver Awareness, Bronx, NY USA. Suny Downstate Med Ctr, Transplantat Serv, Brooklyn, NY 11203 USA. Albert Einstein Coll Med, Div Bioeth, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Mt Sinai Hosp, Pediat Liver Transplant Programs, New York, NY 10029 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Tufts Univ, Sch Med, New England Med Ctr, Div Transplant Surg, Boston, MA 02111 USA. Cleveland Clin, Dept Gen Surg, Cleveland, OH 44106 USA. Cleveland Clin, Transplant Ctr, Cleveland, OH 44106 USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. Gift Life Donor Program, Philadelphia, PA USA. New York Presbyterian Hosp, New York, NY USA. Univ Minnesota, Liver Transplantat Program, Minneapolis, MN USA. Univ Michigan Hlth Syst, Div Transplantat, Ann Arbor, MI USA. Ctr Donat & Transplant, Albany, NY USA. Vanderbilt Univ Sch Med, Dept Surg, Nashville, TN USA. Vanderbilt Univ Sch Med, Div Hepatobiliary Surg & Liver Transplantat, Nashville, TN USA. New York State Task Force Life & Law, New York, NY USA. Westchester Cty Med Ctr, Valhalla, NY 10595 USA. NYU, Med Ctr, New York, NY 10016 USA. New York Ctr Liver Transplantat, E Greenbush, NY USA. US Hlth Resources & Serv Adm, Operat & Anal Branch, Div Transplantat, Healthcare Syst Bur, Rockville, MD 20857 USA. RP Valente, K (reprint author), New York City Dept Hlth, 433 River St,Hedley Bldg,6th Floor, Troy, NY 12180 USA. EM kav02@health.state.ny.us RI Fung, John/A-2679-2012; Valente, Kette/D-5609-2012 NR 2 TC 19 Z9 19 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2005 VL 11 IS 10 BP 1184 EP 1192 DI 10.1002/lt.20569 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 971VT UT WOS:000232413700006 ER PT J AU Schiodt, FV Rossaro, L Stravitz, RT Shakil, AO Chung, RT Lee, WM AF Schiodt, FV Rossaro, L Stravitz, RT Shakil, AO Chung, RT Lee, WM CA Acute Liver Failure Study Grp TI Gc-globulin and prognosis in acute liver failure SO LIVER TRANSPLANTATION LA English DT Article ID FULMINANT HEPATIC-FAILURE; GROUP-SPECIFIC COMPONENT; D-BINDING PROTEIN; VITAMIN-D; SCAVENGER SYSTEM; PLASMA GELSOLIN; EARLY PREDICTOR; UNITED-STATES; SERUM; ACTIN AB Serum concentrations of the actin scavenger Gc-globulin are reduced in acute liver failure (ALF). Prospectively, we tested Gc-globulin's value to predict outcome following ALF using sera from 182 patients with ALF from the U.S. ALF Study Group. Admission serum levels of Gc-globulin (normal range: 350-500 mg/L) were studied by an immunonephelometric method. The median (range) serum Gc-globulin level on admission for the entire group was 91 (5-307) mg/L. Gc-globulin levels were significantly higher in spontaneous survivors than in patients who died or underwent transplantation (113 [5-301] mg/L vs. 73 [5-307] mg/L, P < 0.001). Those surviving non-acetaminophen (paracetamol)-induced ALF without transplantation had higher Gc-globulin levels than nonsurvivors (102 [5-301] mg/L vs. 61 [5-232] mg/L, P = 0.002), whereas there was no significant difference in levels between the groups in patients with acetaminophen-induced ALF. A cutoff level of 80 mg/L in the non-acetaminophen group yielded positive and negative predictive values of 85% and 43%, respectively. The corresponding figures for the King's College criteria were 90% and 49%, respectively. In conclusion, we found that Gc-globulin levels were markedly decreased in patients with ALF; the lowest levels were observed in patients who died or were transplanted. In contrast to previous studies, this study demonstrated that Gc-globulin has prognostic value in patients with non-acetaminophen-induced ALF, in the same range as the King's College criteria. Further refinements of the assay would be necessary to make it more accurate and of practical utility. C1 Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75390 USA. Rigshosp, Dept Gastroenterol CA 2121, DK-2100 Copenhagen, Denmark. Univ Calif Davis, Davis Med Ctr Transplant Med, Sacramento, CA 95817 USA. Virginia Commonwealth Univ, Sect Hepatol, Richmond, VA USA. Univ Pittsburgh, Med Ctr, Ctr Liver Dis, Pittsburgh, PA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Lee, WM (reprint author), Univ Texas, SW Med Ctr, Div Digest & Liver Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM william.lee@utsouthwestern.edu FU NIDDK NIH HHS [R01 DK58369, R03 DK52827, U01 DK058369] NR 32 TC 33 Z9 37 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2005 VL 11 IS 10 BP 1223 EP 1227 DI 10.1002/lt.20437 PG 5 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 971VT UT WOS:000232413700011 PM 16184570 ER PT J AU Shuster, E AF Shuster, E TI Justice at Nuremberg: Leo Alexander and the Nazi doctors' trial SO MEDICAL HISTORY LA English DT Book Review C1 Vet Affairs Med Ctr, Philadelphia, PA USA. RP Shuster, E (reprint author), Vet Affairs Med Ctr, Philadelphia, PA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0025-7273 EI 2048-8343 J9 MED HIST JI Med. Hist. PD OCT PY 2005 VL 49 IS 4 BP 538 EP 539 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 979VV UT WOS:000232974000019 ER PT J AU Smith, CS Golubovskaya, VM Peck, E Xu, LH Monia, BP Yang, XH Cance, WG AF Smith, CS Golubovskaya, VM Peck, E Xu, LH Monia, BP Yang, XH Cance, WG TI Effect of focal adhesion kinase (FAK) downregulation with FAK antisense oligonucleotides and 5-fluorouracil on the viability of melanoma cell lines SO MELANOMA RESEARCH LA English DT Article DE antisense oligonucleotides; apoptosis; chemotherapy; focal adhesion kinase ID BREAST-CANCER CELLS; TYROSINE KINASE; CARCINOMA CELLS; TUMOR-CELLS; PREOPERATIVE TREATMENT; MALIGNANT-MELANOMA; THERAPEUTIC AGENTS; IN-VITRO; APOPTOSIS; DEATH AB Inhibition of focal adhesion kinase (FAK), a non-receptor tyrosine kinase linked to tumour cell survival, causes cell rounding, loss of adhesion and apoptosis in human cancer cell lines. In this study, we tested antisense oligonucleotide inhibitors of FAK, in combination with 5-fluorouracil (5-FU), to increase its sensitivity in human melanoma cell lines. Antisense oligonucleotides directed to the 5' mRNA sequence of FAK and missense control oligonucleotides were used. In BL melanoma cells, treatment with FAK antisense oligonucleotide was associated with a 2.5-fold increase in cell death compared with treatment with control oligonucleotide (33 +/- 2% vs. 13 +/- 3%, P < 0.0001). 5-FU alone had no effect on BL cells (4.4% cell death, P = 0.15). The addition of 5-FU after antisense oligonucleotide resulted in a significant synergistic increase in cell death equal to 69 2% compared with treatments with antisense oligonucleotide alone, 5-FU alone and control oligonucleotide (P < 0.0001). Similar results were found in the C8161 melanoma cell line. In both cell lines, reduction in cell viability was accompanied by an increased loss of adhesion and increased apoptosis that was proportional to the decrease in viability. Treatment with antisense oligonucleotide plus 5-FU resulted in significantly decreased p125(FAK) expression in both C8161 and BL melanoma cell lines, demonstrated by Western blot analyses. These data show that the downregulation of FAK by antisense oligonucleotide combined with 5-FU chemotherapy results in a greater loss of adhesion and greater apoptosis in melanoma cells than treatment with either agent alone, suggesting that the combination may be a potential therapeutic agent for human melanoma in vivo. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Univ Florida, Sch Med, Dept Surg, Gainesville, FL USA. Univ Florida, Dept Biochem & Mol Biol, Dept Surg, Gainesville, FL USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Cance, WG (reprint author), Hlth Sci Ctr, POB 100286,1600 SW Archer Rd, Gainesville, FL 32610 USA. EM cance@surgery.ufl.edu FU NCI NIH HHS [CA65910] NR 39 TC 54 Z9 55 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD OCT PY 2005 VL 15 IS 5 BP 357 EP 362 DI 10.1097/00008390-200510000-00003 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 976PZ UT WOS:000232746900003 PM 16179862 ER PT J AU Cook, JM Elhai, JD Cassidy, EL Ruzek, JI Ram, GD Sheikh, JI AF Cook, JM Elhai, JD Cassidy, EL Ruzek, JI Ram, GD Sheikh, JI TI Assessment of trauma exposure and post-traumatic stress in long-term care veterans: Preliminary data on psychometrics and post-traumatic stress disorder prevalence SO MILITARY MEDICINE LA English DT Article ID PTSD CHECKLIST; OLDER-ADULTS; COMMUNITY; SYMPTOMS; DEMENTIA AB This article reports preliminary data on trauma and post-traumatic stress disorder (PTSD) prevalence, as well as test psychometrics, among 35 cognitively intact veterans residing in long-term care settings. Participants received a traumatic event screening, the Mini-Mental Status Examination, Combat Exposure Scale (CES), PTSD Checklist (PCL), and Mississippi Combat PTSD Scale (M-PTSD). Results demonstrated adequate reliability for the CES, PCL, and M-PTSD for use in these settings, with several significant intercorrelations. A high prevalence of trauma exposure was found, in particular combat. Based on the PCL and M-PTSD, although most veterans did not meet full PTSD diagnostic criteria, a moderate proportion met partial criteria. The need for assessment and treatment of trauma exposure and PTSD in Veterans Affairs long-term care settings is emphasized. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ S Dakota, Disaster Mental Hlth Inst, Vermillion, SD 57069 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Cook, JM (reprint author), Columbia Univ, New York State Psychiat Inst, 1051 Riverside Dr,Box 69, New York, NY 10032 USA. EM jc2676@columbia.edu NR 35 TC 12 Z9 12 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2005 VL 170 IS 10 BP 862 EP 866 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 019JR UT WOS:000235831900011 PM 16435760 ER PT J AU King, R Page, RN Googe, PB Mihm, MC AF King, R Page, RN Googe, PB Mihm, MC TI Lentiginous melanoma: a histologic pattern of melanoma to be distinguished from lentiginous nevus SO MODERN PATHOLOGY LA English DT Article DE melanoma; lentiginous nevus; lentigo maligna; elderly; dysplastic nevus ID DIAGNOSTIC DIFFICULTIES; MALIGNANT-MELANOMA AB Atypical lentiginous melanocytic proliferations in elderly patients continue to pose a diagnostic dilemma with lesions variably categorized as dysplastic nevus, atypical junctional nevus, melanoma in situ ( early or evolving) and premalignant melanosis. We present pigmented lesions from 16 patients ( seven male and nine female) and with the exception of one case, all were older than 50 years of age. The anatomical sites included trunk ( 7), head and neck ( 6) and upper extremity ( 3). The clinical diagnosis was variable and included lentigo maligna, atypical nevus, pigmented basal cell carcinoma, seborrheic keratosis and lentigo. The initial biopsies mimicked lentiginous nevus or dysplastic nevus and were characterized by a lentiginous proliferation of melanocytes at the dermoepidermal junction both as single cells and as small nests with areas of confluent growth, extending to the edges of the biopsy. The retiform epidermis was maintained and pagetoid spread of melanocytes was not prominent in hematoxylin- and eosin- stained sections. Dermal fibrosis was variably present and the melanocytic proliferation demonstrated cytological atypia. The subsequent re- excisions demonstrated similar atypical melanocytic proliferation occurring over a broad area flanking the prior biopsy sites. The diagnosis of melanoma was more easily recognized in the complete excision specimens. Immunohistochemical stains for Mitf and Mart- 1 highlighted the extent of the basalar melanocytic proliferation as well as foci of pagetoid spread by melanocytes. Familiarity with this pattern of early melanoma should facilitate proper classification of lentiginous melanocytic proliferations in biopsies from older adults. C1 Knoxville Dermatopathol Lab, Knoxville, TN 37919 USA. Univ Tennessee, Grad Sch Med, Dept Pathol, Knoxville, TN USA. Vanderbilt Univ, Dept Pathol, Nashville, TN USA. Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. RP King, R (reprint author), Knoxville Dermatopathol Lab, 315 Erin Dr, Knoxville, TN 37919 USA. EM rking@labpath.com OI Googe, Paul/0000-0002-9185-3548 NR 12 TC 31 Z9 31 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2005 VL 18 IS 10 BP 1397 EP 1401 DI 10.1038/modpathol.3800454 PG 5 WC Pathology SC Pathology GA 968EV UT WOS:000232145600016 PM 15976811 ER PT J AU Ueki, K Kondo, T Kahn, CR AF Ueki, K Kondo, T Kahn, CR TI Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms (vol 24, pg 5434, 2004) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Ueki, K (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2005 VL 25 IS 19 BP 8762 EP 8762 DI 10.1128/MCB.25.19.8762.2005 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 967AH UT WOS:000232063400031 ER PT J AU Mills, CD Bitler, JL Woolf, CJ AF Mills, CD Bitler, JL Woolf, CJ TI Role of the peripheral benzodiazepine receptor in sensory neuron regeneration SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID DIAZEPAM-BINDING INHIBITOR; DORSAL-ROOT GANGLION; RAT SCIATIC-NERVE; CHOLESTEROL-DEPENDENT MODULATION; ACUTE REGULATORY PROTEIN; IN-VIVO; CONDITIONING LESION; AXONAL REGENERATION; NEURITE OUTGROWTH; GROWTH-FACTOR AB Peripheral benzodiazepine receptor (PBR) expression increases in small dorsal root ganglion (DRG) sensory neurons after peripheral nerve injury. To determine the functional significance of this induction. we evaluated the effects of PBR ligands on rodent sensory axon outgrowth. In vitro, Ro5-4864, a PBR agonist, enhanced outgrowth only of small peripherin-positive DRG neurons. When DRG cells were preconditioned into an active growth state by a prior peripheral nerve injury Ro5-4864 augmented and PK 11195, a PBR antagonist, blocked the injury-induced increased outgrowth. In vivo, Ro5-4864 increased the initiation of regeneration after a sciatic nerve crush injury and the number of GAP-43-positive axons in the distal nerve while PK 11195 inhibited the enhanced growth produced by a preconditioning lesion. These results show that PBR has a role in the early regenerative response of small caliber sensory axons, the preconditioning effect, and that PBR agonists enhance sensory axon regeneration. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Mills, CD (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, 149 13th St, Charlestown, MA 02129 USA. EM emills@hms.harvard.edu FU NINDS NIH HHS [NS45459, NS038253] NR 74 TC 34 Z9 34 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD OCT PY 2005 VL 30 IS 2 BP 228 EP 237 DI 10.1016/j.mcn.2005.07.010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 967AP UT WOS:000232064200007 PM 16099172 ER PT J AU Butts, BD Hudson, HR Linseman, DA Le, SS Ryan, KR Bouchard, RJ Heidenreich, KA AF Butts, BD Hudson, HR Linseman, DA Le, SS Ryan, KR Bouchard, RJ Heidenreich, KA TI Proteasome inhibition elicits a biphasic effect on neuronal apoptosis via differential regulation of pro-survival and pro-apoptotic transcription factors SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CEREBELLAR GRANULE NEURONS; CYTOCHROME-C RELEASE; UBIQUITIN-PROTEIN LIGASE; KAPPA-B ACTIVATION; ENHANCER FACTOR 2A; GROWTH-FACTOR-I; FACTOR 2D MEF2D; PARKINSONS-DISEASE; PROTEOLYTIC PATHWAY; CORTICAL-NEURONS AB The role of the proteasome in neuronal apoptosis is poorly understood since both anti- and pro-apoptotic effects result from proteasome inhibition. We studied the effects of proteasome inhibition in cultured rat cerebellar granule neurons. Acute exposure to proteasome inhibitors MG-132 and lactacystin blocked caspase activation induced by removal of depolarizing medium. However, chronic treatment with MG-132 activated caspases in neurons maintained in depolarizing potassium. The biphasic effect of MG-132 was hypothesized to be due to differential degradation of anti- and pro-apoptotic proteins. Accordingly, acute exposure to MG-132 inhibited the hyperphosphorylation, loss of DNA binding, ubiquitination, and degradation of the pro-survival transcription factor MEF2D induced by removal of depolarizing medium. In contrast, chronic exposure to MG-132 increased the expression and phosphorylation of c-Jun, elevated levels of the pro-apoptotic protein Bim, and triggered neuronal apoptosis, even in the presence of depolarizing medium. Thus, proteasome inhibition exerts an acute pro-survival action by stabilizing MEF2 transcription factors. However, chronic proteasome inhibition causes a build-up of phosphorylated c-Jun and Bim, which eventually overwhelms the effects of MEF2 and triggers apoptosis. (c) 2005 Published by Elsevier Inc. C1 Univ Colorado, Hlth Sci Ctr, Aurora, CO 80045 USA. Denver VA Med Ctr, Denver, CO 80220 USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Aurora, CO 80045 USA. EM kim.heidenreich@uchsc.edu NR 50 TC 28 Z9 30 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD OCT PY 2005 VL 30 IS 2 BP 279 EP 289 DI 10.1016/j.mcn.2005.07.011 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 967AP UT WOS:000232064200011 PM 16112871 ER PT J AU Zhu, J Balan, V Bronisz, A Balan, K Sun, HR Leicht, DT Luo, ZJ Qin, J Avruch, J Tzivion, G AF Zhu, J Balan, V Bronisz, A Balan, K Sun, HR Leicht, DT Luo, ZJ Qin, J Avruch, J Tzivion, G TI Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIVATED PROTEIN-KINASE; IN-VIVO; PATHWAY; MUTATIONS; MECHANISM; MEMBRANE; ONCOGENE; FEEDBACK; TARGET; CANCER AB The Ras-Raf-MAPK cascade is a key growth-signaling pathway and its uncontrolled activation results in cell transformation. Although the general features of the signal transmission along the cascade are reasonably defined, the mechanisms underlying Raf activation remain incompletely understood. Here, we show that Raf-1 dephosphorylation, primarily at epidermal growth factor (EGF)-induced sites, abolishes Raf-1 kinase activity. Using mass spectrometry, we identified five novel in vivo Raf-1 phosphorylation sites, one of which., S471, is located in subdomain VIB of Raf-1 kinase domain. Mutational analyses demonstrated that Raf-1 S,471 is critical for Raf-1 kinase activity and for its interaction with mitogen-activated protein kinase kinase (MEK). Similarly, mutation of the corresponding B-Raf site, S578, resulted in an inactive kinase, suggesting that the same Raf-1 and B-Raf phosphorylation is needed for Raf kinase activation. Importantly, the naturally occurring, cancer-associated B-Raf activating mutation V599E suppressed the S578A mutation, suggesting that introducing a charged residue at this region eliminates the need for an activating phosphorylation. Our results demonstrate an essential role of specific EGF-induced Raf-1 phosphorylation sites in Raf-1 activation, identify Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities, and point to the possibility that the V599E mutation activates B-Raf by mimicking a phosphorylation at the S578 site. C1 Texas A&M Univ, Hlth Sci Ctr, Inst Cardiovasc Res, Temple, TX 76504 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Diabet & Metab Res Unit, Boston, MA 02118 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Biol Mol, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Tzivion, G (reprint author), Texas A&M Univ, Hlth Sci Ctr, Inst Cardiovasc Res, Temple, TX 76504 USA. EM tziviong@karmanos.org RI Tzivion, Guri/D-8954-2011 FU NIGMS NIH HHS [R01 GM-067134, R01 GM067134] NR 49 TC 25 Z9 26 U1 0 U2 2 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 OCT PY 2005 VL 16 IS 10 BP 4733 EP 4744 DI 10.1091/mbc.E05-02-0090 PG 12 WC Cell Biology SC Cell Biology GA 969TM UT WOS:000232257700024 PM 16093354 ER PT J AU Roig, J Groen, A Caldwell, J Avruch, J AF Roig, J Groen, A Caldwell, J Avruch, J TI Active Nercc1 protein kinase concentrates at centrosomes early in mitosis and is necessary for proper spindle assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID XENOPUS EGG EXTRACTS; NIMA-RELATED KINASE; KIDNEY-DISEASE; FAMILY KINASE; RAN; GTPASE; PROGRESSION; TARGET; MOUSE; CELLS AB The Nercc1 protein kinase autoactivates in vitro and is activated in vivo during mitosis. Autoactivation in vitro requires phosphorylation of the activation loop at threonine 210. Mitotic activation of Nercc1 in mammalian cells is accompanied by Thr210 phosphorylation and involves a small fraction of total Nercc1. Mammalian Nercc1 coimmunoprecipitates gamma-tubulin and the activated Nercc1 polypeptides localize to the centrosomes and spindle poles during early mitosis, suggesting that active Nercc has important functions at the microtubular organizing center during cell division. To test this hypothesis, we characterized the Xenopus Nercc1 orthologue (XNercc). XNercc endogenous to meiotic egg extracts coprecipitates a multiprotein complex that contains gamma-tubulin and several components of the gamma-tubulin ring complex and localizes to the poles of spindles formed in vitro. Reciprocally, immunoprecipitates of the gamma-tubulin ring complex polypeptide Xgrip109 contain XNercc. Immunodepletion of XNercc from egg extracts results in delayed spindle assembly, fewer bipolar spindles, and the appearance of aberrant microtubule structures, aberrations corrected by addition of purified recombinant XNercc. XNercc immunodepletion also slows aster assembly induced by Ran-GTP, producing Ran-asters of abnormal size and morphology. Thus, Nercc1 contributes to both the centrosomal and the chromatin/Ran pathways that collaborate in the organization of a bipolar spindle. C1 Massachusetts Gen Hosp, Dept Mol Biol & Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. MDS Proteom, Charlottesville, VA 22911 USA. RP Massachusetts Gen Hosp, Dept Mol Biol & Med Serv, Boston, MA 02114 USA. EM roig@molbio.mgh.harvard.edu; avruch@helix.mgh.harvard.edu OI Roig, Joan/0000-0002-3872-4712 FU NIDDK NIH HHS [DK-17776, R37 DK017776] NR 28 TC 40 Z9 40 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2005 VL 16 IS 10 BP 4827 EP 4840 DI 10.1091/mbc.E0-04-0315 PG 14 WC Cell Biology SC Cell Biology GA 969TM UT WOS:000232257700031 PM 16079175 ER PT J AU Lu, H Wu, JY Kudo, T Ohno, T Graham, DY Yamaoka, Y AF Lu, H Wu, JY Kudo, T Ohno, T Graham, DY Yamaoka, Y TI Regulation of interleukin-6 promoter activation in gastric epithelial cells infected with Helicobacter pylori SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-KAPPA-B; TRANSCRIPTIONAL ACTIVATION; PATHOGENICITY ISLAND; VIRULENCE FACTORS; C-FOS; MUCOSAL INTERLEUKIN-8; SIGNAL-TRANSDUCTION; MESSENGER-RNA; FACTOR-ALPHA AB The regulation of Helicobacter pylori induced interleukin (IL)-6 in the gastric epithelium remains unclear. Primary gastric epithelial cells and MKN28 cells were cocultured with H. pylori and its isogenic cag pathogenicity island (PAI) mutant and/or oipA mutants. H. pylori infection-induced IL-6 mRNA expression and IL-6 protein production, which was further enhanced by the cag PAI and OipA. Luciferase reporter gene assays and electrophoretic mobility shift assays showed that full IL-6 transcription required binding sites for nuclear factor-kappa B (NF-kappa B), cAMP response element (CRE), CCAAT/enhancer binding protein (C/EBP), and activator protein (AP)-1. The cag PAI and OipA were involved in binding to NF-kappa B AP-1, CRE, and C/EBP sites. The cag PAI activated the extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) pathways; OipA activated the p38 pathway. Transfection of dominant negative G-protein confirmed roles for Raf, Rac1, and RhoA in IL-6 induction. Overall, the cag PAI-related IL-6 signal transduction pathway involved the Ras/Raf/MEK1/2/ERK/AP-1/CRE pathway and the JNK/AP-1/CRE pathway; the OipA-related pathway is p38/AP-1/CRE and both the cag PAI and OipA appear to be involved in the RhoA/Rac1/NF-kappa B pathway. Combination of different pathways by the cag PAI and OipA will lead to the maximum IL-6 induction. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Kyoto Prefectural Univ Med, Dept Gastroenterol & Hepatol, Kyoto 6020841, Japan. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [P30 DK056338, DK56338, R01 DK062813, R01 DK062813-03, R01 DK62813] NR 47 TC 54 Z9 56 U1 0 U2 1 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 OCT PY 2005 VL 16 IS 10 BP 4954 EP 4966 DI 10.1091/mbc.E05-05-0426 PG 13 WC Cell Biology SC Cell Biology GA 969TM UT WOS:000232257700041 PM 16030249 ER PT J AU Shi, YJ Yan, HJ Frost, P Gera, J Lichtenstein, A AF Shi, YJ Yan, HJ Frost, P Gera, J Lichtenstein, A TI Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TUMOR-CELLS; PHOSPHORYLATION; SUBSTRATE-1; PATHWAY; INTERLEUKIN-6; DEGRADATION; MODULATION; RESISTANCE; MECHANISM; PROTEINS AB Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin and CCI-779, have shown preclinical potential as therapy for multiple myeloma. By inhibiting expression of cell cycle proteins, these agents induce G, arrest. However, by also inhibiting an mTOR-dependent serine phosphorylation of insulin receptor substrate-1 (IRS-1), they may enhance insulin-like growth factor-1 (IGF-1) signaling and downstream phosphatidylinositol 3-kinase (PI3K)/AKT activation. This may be a particular problem in multiple myeloma where IGF-1-induced activation of AKT is an important antiapoptotic cascade. We, therefore, studied AKT activation in multiple myeloma cells treated with mTOR inhibitors. Rapamycin enhanced basal AKT activity, AKT phosphorylation, and PI3K activity in multiple myeloma cells and prolonged activation of AKT induced by exogenous IGF-I. CCI-779, used in a xenograft model, also resulted in multiple myeloma cell AKT activation in vivo. Blockade of lGF-I receptor function prevented rapamycin's activation of AKT. Furthermore, rapamycin prevented serine phosphorylation of IRS-1, enhanced IRS-1 association with IGF-I receptors, and prevented IRS-1 degradation. Although similarly blocking IRS-1 degradation, proteasome inhibitors did not activate AKT. Thus, mTOR inhibitors activate PI3-K/AKT in multiple myeloma cells; activation depends on basal IGF-R signaling; and enhanced IRS-1/IGF-I receptor interactions secondary to inhibited IRS-1 serine phosphorylation may play a role in activation of the cascade. In cotreatment experiments, rapamycin inhibited myeloma cell apoptosis induced by PS-341. These results provide a caveat for future use of mTOR inhibitors in myeloma patients if they are to be combined with apoptosis-inducing agents. C1 Univ Calif Los Angeles, W Los Angeles Vet Adm, Med Ctr, Div Hematol Oncol, Los Angeles, CA USA. Univ Calif Los Angeles, Johnson Comprehens Canc Ctr, Los Angeles, CA USA. RP Lichtenstein, A (reprint author), Vet Adm W Los Angeles Hosp, W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM alichten@ucla.edu OI Frost, Patrick/0000-0003-3348-5983 FU NCI NIH HHS [CA096920, CA111448-01] NR 25 TC 216 Z9 223 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2005 VL 4 IS 10 BP 1533 EP 1540 DI 10.1158/1535-7163.MCT-05-0068 PG 8 WC Oncology SC Oncology GA 974AS UT WOS:000232564300009 PM 16227402 ER PT J AU Dieguez-Acuna, FJ Gerber, SA Kodama, S Elias, JE Beausoleil, SA Faustman, D Gygi, SP AF Dieguez-Acuna, FJ Gerber, SA Kodama, S Elias, JE Beausoleil, SA Faustman, D Gygi, SP TI Characterization of mouse spleen cells by subtractive proteomics SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TANDEM MASS-SPECTROMETRY; PROTEINS; YEAST; IDENTIFICATION; MACHINERY; COMPLEX AB Major analytical challenges encountered by shotgun proteome analysis include both the diversity and dynamic range of protein expression. Often new instrumentation can provide breakthroughs in areas where other analytical improvements have not been successful. In the current study, we utilized new instrumentation (LTQ FT) to characterize complex protein samples by shotgun proteomics. Proteomic analyses were performed on murine spleen tissue separated by magnetic beads into distinct CD45(-) and CD45(+) cell populations. Using shotgun protein analysis we identified similar to 2,000 proteins per cell group by over 12,000 peptides with mass deviations of less than 4.5 ppm. Datasets obtained by LTQ FT analysis provided a significant increase in the number of proteins identified and greater confidence in those identifications and improved reproducibility in replicate analyses. Because CD45(-) and not CD45(+) cells are able to regenerate functional pancreatic islet cells in a mouse model of type I diabetes, protein expression was further compared by a subtractive proteomic approach in search of an exclusive protein expression profile in CD45(-) cells. Characterization of the proteins exclusively identified in CD45(-) cells was performed using gene ontology terms via the Javascript GoMiner. The CD45(+) cell subset readily revealed proteins involved in development, suggesting the persistence of a fetal stem cell in an adult animal. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Gygi, SP (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. OI Gerber, Scott/0000-0002-2964-5051 FU NHGRI NIH HHS [HG003456]; NIDDK NIH HHS [TGT32DK07028] NR 23 TC 40 Z9 42 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2005 VL 4 IS 10 BP 1459 EP 1470 DI 10.1074/mcp.M500137-MCP200 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 969BH UT WOS:000232207900004 PM 16037072 ER PT J AU Georgescu, SP Li, JH Lu, Q Karas, RH Brown, M Mendelsohn, ME AF Georgescu, SP Li, JH Lu, Q Karas, RH Brown, M Mendelsohn, ME TI Modulator recognition factor 1, an AT-Rich interaction domain family member, is a novel corepressor for estrogen receptor alpha SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NUCLEAR HORMONE RECEPTORS; CO-REPRESSOR; DEPENDENT TRANSCRIPTION; ARID PROTEINS; COACTIVATOR; ACTIVATION; DIFFERENTIATION; MECHANISMS; EXPRESSION; COMPLEXES AB Cardiovascular tissues are important targets of estrogen action. Vascular cells express the two known estrogen receptors ( ERs), ER alpha and ER beta, ligand-activated transcription factors that regulate gene transcription through interactions with both coactivator and corepressor molecules. To isolate ER alpha coregulators in vascular cells, we performed a yeast two-hybrid screen for ER alpha-interacting proteins using a human aorta library. Here we report the identification of modulator recognition factor 1 ( MRF1) as an ER alpha-interacting corepressor protein. Full-length MRF1 binds to both the N terminus and the C terminus of ER alpha. ER alpha and MRF1 coimmunoprecipitate in an estradiol-independent manner, and recombinant ER alpha binds to both full-length and COOH-terminal MRF1 in the absence of estradiol. MRF1 also interacts in a ligand-dependent manner with thyroid receptor alpha, retinoid X receptor alpha, and androgen receptor, and in a ligand-independent manner with ER alpha and the retinoic acid receptor. MRF1 RNA is highly expressed in aorta, heart, skeletal muscle, and liver. MRF1 has intrinsic repressor activity in an in vitro GAL reporter assay. Transient transfection studies show that MRF1 represses transcription by ER alpha activated by estradiol in a dose-dependent manner, as well as by the selective ER modulators 4-hydroxy-tamoxifen and raloxifene. MRF1 repression is not influenced by pharmacological inhibition of histone deacetylase. These data identify MRF1 as a repressor of ER alpha-mediated transcriptional activation and support a role for MRF1 in regulating ER-dependent gene expression in cardiovascular and other cells. C1 Tufts Univ, Sch Med, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mendelsohn, ME (reprint author), Tufts Univ, Sch Med, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. EM mmendelsohn@tufts-nemc.org OI Brown, Myles/0000-0002-8213-1658 FU NHLBI NIH HHS [5P50HL063494, 5R01HL056069] NR 28 TC 14 Z9 15 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2005 VL 19 IS 10 BP 2491 EP 2501 DI 10.1210/me.2004-0311 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 967UO UT WOS:000232116900006 PM 15941852 ER PT J AU Fan, JB Sklar, P AF Fan, JB Sklar, P TI Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE schizophrenia; meta-analysis; SLC6A4; 5-HTTLPR; STin2 VNTR ID TANDEM REPEAT POLYMORPHISM; FAMILY-BASED ASSOCIATION; AFFECTIVE-DISORDERS; PSYCHIATRIC-DISORDERS; TARDIVE-DYSKINESIA; PERSONALITY-TRAITS; CLOZAPINE RESPONSE; ALLELIC VARIANTS; BIPOLAR DISORDER; PROMOTER REGION AB The serotonin transporter gene (SLC6A4) is a candidate gene for schizophrenia based on serotonin transporter's crucial role in serotonergic neurotransmission. However, association studies have produced conflicting results regarding the association between two common SLC6A4 gene polymorphisms, the promoter insertion/ deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR) polymorphisms, and schizophrenia susceptibility. To further elucidate the putative association between the two SLC6A4 gene polymorphisms and schizophrenia susceptibility, we performed a meta-analysis based on all original published association studies between schizophrenia and the 5-HTTLPR and STin2 VNTR polymorphisms published before April 2004. Our analyses showed no statistically significant evidence for the association between the Short allele of the 5-HTTLPR polymorphism and schizophrenia ( random-effects pooled odds ratio ( OR) 0.99, 95% Confidence Interval ( CI) 0.92 - 1.07, Z = - 0.23, P = 0.82) from 19 population-based association studies consisting of 2990 case and 3875 control subjects. However, highly significant evidence for association between the STin2.12 allele of the STin2 VNTR polymorphism ( random-effects pooled OR 1.24, 95% CI 1.11 - 1.38, Z = 3.82, P = 0.00014) and schizophrenia was found from 12 population-based association studies consisting of 2177 cases and 2369 control subjects. Our meta-analysis suggests that the STin2.12 allele of the STin2 VNTR polymorphism is likely a risk factor for schizophrenia susceptibility. Our data imply that following completion of the International HapMap Project, a comprehensive evaluation of a set of markers that fully characterize the linkage disequilibrium relationships at the SLC6A4 gene should be tested in large well-characterized clinical samples in order to understand the role of this gene in schizophrenia susceptibility. C1 Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Charlestown, MA 02129 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Sklar, P (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 149 13th St, Charlestown, MA 02129 USA. EM sklar@psych.mgh.harvard.edu NR 86 TC 87 Z9 90 U1 2 U2 5 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 OCT PY 2005 VL 10 IS 10 BP 928 EP 938 DI 10.1038/sj.mp.4001690 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 968FC UT WOS:000232146300007 PM 15940296 ER PT J AU Burns, CG Milan, DJ Grande, EJ Rottbauer, W MacRae, CA Fishman, MC AF Burns, CG Milan, DJ Grande, EJ Rottbauer, W MacRae, CA Fishman, MC TI High-throughput assay for small molecules that modulate zebrafish embryonic heart rate SO NATURE CHEMICAL BIOLOGY LA English DT Article ID CARDIOVASCULAR-SYSTEM; VERTEBRATE; DISCOVERY; MUTATION; MODEL AB To increase the facility and throughput of scoring phenotypic traits in embryonic zebrafish, we developed an automated micro-well assay for heart rate using automated fluorescence microscopy of transgenic embryos expressing green fluorescent protein in myocardium. The assay measures heart rates efficiently and accurately over a large linear dynamic range, and it rapidly characterizes dose dependence and kinetics of small molecule-induced changes in heart rate. This is the first high-throughput micro-well assay for organ function in an intact vertebrate. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Burns, CG (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, 149 13th St, Boston, MA 02129 USA. EM gburns@cvrc.mgh.harvard.edu FU NHLBI NIH HHS [K08 HL068711, 5T32HL07208-26]; NIA NIH HHS [1K01AG023562-01, K01 AG023562]; NIGMS NIH HHS [R21 GM075946]; NINDS NIH HHS [1R03NS050806-01, R03 NS050806] NR 15 TC 169 Z9 178 U1 5 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD OCT PY 2005 VL 1 IS 5 BP 263 EP 264 DI 10.1038/nchembio732 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 975GN UT WOS:000232649100009 PM 16408054 ER PT J AU Deswal, A Mann, DL AF Deswal, A Mann, DL TI Can valsartan reduce the occurrence of atrial fibrillation in heart failure patients? SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material DE angiotensin receptor blocker; atrial fibrillation; heart failure; valsartan ID VENTRICULAR DYSFUNCTION; PREVENTION C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Deswal, A (reprint author), VA Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM adeswal@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 NR 6 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2005 VL 2 IS 10 BP 502 EP 503 DI 10.1038/ncpcardio0325 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 966UF UT WOS:000232046900004 PM 16186843 ER PT J AU Armoundas, AA Hohnloser, SH Ikeda, T Cohen, RJ AF Armoundas, AA Hohnloser, SH Ikeda, T Cohen, RJ TI Can microvolt T-wave alternans testing reduce unnecessary defibrillator implantation? SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Review DE alternans; implantable cardioverter-defibrillator; primary prevention; sudden cardiac death ID SIGNAL-AVERAGED ELECTROCARDIOGRAPHY; ARRHYTHMIA RISK STRATIFICATION; CONGESTIVE-HEART-FAILURE; SUDDEN CARDIAC DEATH; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; ELECTRICAL ALTERNANS; CARDIOVERTER-DEFIBRILLATOR; EVENTS; VULNERABILITY AB The Multicenter Automatic Defibrillator Implantation Trial 11 (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) have established that patients with a reduced ejection fraction gain an overall mortality benefit from prophylactic implantable cardioverter-defibrillator therapy. Only a small proportion of the patients in these studies, however, have received life-saving therapy from the defibrillator. Because defibrillator therapy is invasive and expensive, patients with a low ejection fraction would benefit from effective risk stratification so that defibrillator therapy was used only in those at significant risk. In this review, we analyze prospective clinical trials that have evaluated microvolt T-wave alternans (MTWA) testing as a predictor of ventricular tachyarrhythmic events in populations of patients similar to those studied in MADIT Iota Iota or SCD-HeFT; that is, patients with a reduced ejection fraction who were not selected on the basis of a history of ventricular tachyarrhythmics. In these studies, the average annual rate of fatal and nonfatal ventricular tachyarrhythmic events among the patients who tested negative for MTWA was around 1%. This rate is so low that it is unlikely that such patients would benefit from implantable cardioverter-defibrillator therapy. The mortality, moreover, was lower among MTWA-negative patients who did not receive implantable defibrillators than that observed in the MADIT 11 and SCD-HeFT patients who received implantable cardioverter-defibrillators. In response, patients with a low ejection fraction who are being considered for implantable cardioverterdefibrillator therapy should undergo MTWA testing as part of their evaluation. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Frankfurt, D-6000 Frankfurt, Germany. Kyorin Univ, Sch Med, Mitaka, Tokyo, Japan. RP Cohen, RJ (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, Room E25-335A,45 Carleton St, Cambridge, MA 02142 USA. EM rjcohen@mit.edu NR 30 TC 27 Z9 28 U1 1 U2 2 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 OCT PY 2005 VL 2 IS 10 BP 522 EP 528 DI 10.1038/ncpcardio0323 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 966UF UT WOS:000232046900011 PM 16186850 ER PT J AU Kuhlenbaumer, G Hannibal, MC Nelis, E Schirmacher, A Verpoorten, N Meuleman, J Watts, GDJ De Vriendt, E Young, P Stogbauer, F Halfter, H Irobi, J Goossens, D Del-Favero, J Betz, BG Hor, H Kurlemann, G Bird, TD Airaksinen, E Mononen, T Serradell, AP Prats, JM Van Broeckhoven, C De Jonghe, P Timmerman, V Ringelstein, EB Chance, PF AF Kuhlenbaumer, G Hannibal, MC Nelis, E Schirmacher, A Verpoorten, N Meuleman, J Watts, GDJ De Vriendt, E Young, P Stogbauer, F Halfter, H Irobi, J Goossens, D Del-Favero, J Betz, BG Hor, H Kurlemann, G Bird, TD Airaksinen, E Mononen, T Serradell, AP Prats, JM Van Broeckhoven, C De Jonghe, P Timmerman, V Ringelstein, EB Chance, PF TI Mutations in SEPT9 cause hereditary neuralgic amyotrophy SO NATURE GENETICS LA English DT Article ID MAMMALIAN SEPTIN; CHROMOSOME 17Q25; HNA LOCUS; MICROTUBULES; REFINEMENT; GENE AB Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis. C1 Univ Munster, Dept Neurol, D-48149 Munster, Germany. Univ Munster, Leibniz Inst Atherosclerosis Res, D-48149 Munster, Germany. Univ Antwerp VIB, Dept Mol Genet, B-2020 Antwerp, Belgium. Univ Washington, Dept Pediat, Div Genet & Dev Med, Seattle, WA 98195 USA. Univ Munster, Dept Pediat Neurol, D-4400 Munster, Germany. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Kuopio, Dept Paediat, FIN-70211 Kuopio, Finland. Kuopio Univ Hosp, Dept Clin Genet, SF-70210 Kuopio, Finland. Autonome Univ Barcelona, Hosp Mar, Dept Neurol, Barcelona, Spain. Hosp Cruces, Div Child Neurol, Baracaldo, Basque Country, Spain. Univ Antwerp Hosp, Div Neurol, Antwerp, Belgium. RP Kuhlenbaumer, G (reprint author), Univ Munster, Dept Neurol, Domagkstr 3, D-48149 Munster, Germany. EM gkuhlen@uni-muenster.de RI Kuhlenbaumer, Gregor/A-5110-2009; OI Del Favero, jurgen/0000-0002-7427-7489 NR 12 TC 105 Z9 112 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2005 VL 37 IS 10 BP 1044 EP 1046 DI 10.1038/ng1649 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 968TP UT WOS:000232185600014 PM 16186812 ER PT J AU Gupta, PB Kuperwasser, C Brunet, JP Ramaswamy, S Kuo, WL Gray, JW Naber, SP Weinberg, RA AF Gupta, PB Kuperwasser, C Brunet, JP Ramaswamy, S Kuo, WL Gray, JW Naber, SP Weinberg, RA TI The melanocyte differentiation program predisposes to metastasis after neoplastic transformation SO NATURE GENETICS LA English DT Article ID TYROSINE KINASE RECEPTOR; NEURAL CREST; MALIGNANT-MELANOMA; LESS-THAN-OR-EQUAL-TO-1 MM; TUMOR PROGRESSION; EPITHELIAL-CELLS; NERVOUS-SYSTEM; BREAST-CANCER; GENE-TRANSFER; LYMPH-NODES AB The aggressive clinical behavior of melanoma suggests that the developmental origins of melanocytes in the neural crest might be relevant to their metastatic propensity. Here we show that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, whereas human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Notably, these melanomas have a metastasis spectrum similar to that observed in humans with melanoma. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi shows that the expression pattern of Slug, a master regulator of neural crest cell specification and migration, correlates with those of other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Anat & Cellular Biol, Boston, MA 02111 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Radiat Oncol, Boston, MA 02111 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu FU NCI NIH HHS [R01 CA078461] NR 42 TC 259 Z9 262 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2005 VL 37 IS 10 BP 1047 EP 1054 DI 10.1038/ng1634 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 968TP UT WOS:000232185600015 PM 16142232 ER PT J AU Ausubel, FM AF Ausubel, FM TI Are innate immune signaling pathways in plants and animals conserved? SO NATURE IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; ORYZAE PV.-ORYZAE; BACTERIAL ELICITOR FLAGELLIN; CAENORHABDITIS-ELEGANS; PEPTIDOGLYCAN RECOGNITION; DISEASE RESISTANCE; DROSOPHILA TOLL; GENE FAMILY; ANTIBACTERIAL DEFENSE; ARABIDOPSIS-THALIANA AB Although adaptive immunity is unique to vertebrates, the innate immune response seems to have ancient origins. Common features of innate immunity in vertebrates, invertebrate animals and plants include defined receptors for microbe-associated molecules, conserved mitogen-associated protein kinase signaling cascades and the production of antimicrobial peptides. It is commonly reported that these similarities in innate immunity represent a process of divergent evolution from an ancient unicellular eukaryote that pre-dated the divergence of the plant and animal kingdoms. However, at present, data suggest that the seemingly analogous regulatory modules used in plant and animal innate immunity are a consequence of convergent evolution and reflect inherent constraints on how an innate immune system can be constructed. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu NR 90 TC 451 Z9 477 U1 11 U2 113 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2005 VL 6 IS 10 BP 973 EP 979 DI 10.1038/ni1253 PG 7 WC Immunology SC Immunology GA 966NR UT WOS:000232027200015 PM 16177805 ER PT J AU Santambrogio, L Potolicchio, I Fessler, SP Wong, SH Raposo, G Strominger, JL AF Santambrogio, L Potolicchio, I Fessler, SP Wong, SH Raposo, G Strominger, JL TI Involvement of caspase-cleaved and intact adaptor protein 1 complex in endosomal remodeling in maturing dendritic cells SO NATURE IMMUNOLOGY LA English DT Article ID CLASS-II TRANSPORT; DOMAIN-CONTAINING PROTEIN; INVARIANT CHAIN; NITRIC-OXIDE; GAMMA-ADAPTIN; ERYTHROID-DIFFERENTIATION; ANTIGEN PRESENTATION; SORTING SIGNALS; GOLGI NETWORK; ACTIVATION AB The involvement of the tetrameric adaptor protein 1 (AP-1) complex in protein sorting in intracellular compartments is not yet completely defined. Here we report that in immature dendritic cells, the beta 1- and gamma-subunits of AP-1 underwent caspase 3-catalyzed cleavage in their hinge regions, resulting in removal of the C-terminal 'ear' domains. Cleavage was inhibited by lipopolysaccharide or caspase inhibitors, each of which led to maturation of the dendritic cells, demonstrated by endosomal remodeling and an increase in surface expression of peptide-loaded major histocompatibility complex class II. Overexpression of similarly truncated AP-1 together with 'silencing' of the endogenous genes in immature dendritic cells did not compromise delivery of major histocompatibility complex class II invariant chain to endosomal compartments. However, after lipopolysaccharide- induced maturation, overexpression of truncated AP-1 and 'silencing' of endogenous genes did result in the anomalous surface accumulation of invariant chain and the peptide-editing molecule H2-DM. Thus, at least one function for intact AP-1 is to retain some proteins in endosomes during the dendritic cell maturation process in which others are allowed to egress to the cell surface. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. CNRS, UMR 144, Inst Curie, F-75005 Paris, France. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Strominger, JL (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM lsantamb@aecom.yu.edu FU NIAID NIH HHS [AI48832, AI49524] NR 51 TC 56 Z9 59 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2005 VL 6 IS 10 BP 1020 EP 1028 DI 10.1038/ni1250 PG 9 WC Immunology SC Immunology GA 966NR UT WOS:000232027200021 PM 16170319 ER PT J AU Cavanagh, LL Bonasio, R Mazo, IB Halin, C Cheng, GY van der Velden, AWM Cariappa, A Chase, C Russell, P Starnbach, MN Koni, PA Pillai, S Weninger, W von Andrian, UH AF Cavanagh, LL Bonasio, R Mazo, IB Halin, C Cheng, GY van der Velden, AWM Cariappa, A Chase, C Russell, P Starnbach, MN Koni, PA Pillai, S Weninger, W von Andrian, UH TI Activation of bone marrow-resident memory T cells by circulating, antigen-bearing dendritic cells SO NATURE IMMUNOLOGY LA English DT Article ID LYMPH-NODES; IN-VIVO; ADHESION MOLECULE-1; ENDOTHELIAL SELECTINS; MIGRATORY PROPERTIES; IMMUNE-RESPONSES; THORACIC DUCT; MOUSE; BLOOD; MICE AB Dendritic cells (DCs) carry antigen from peripheral tissues via lymphatics to lymph nodes. We report here that differentiated DCs can also travel from the periphery into the blood. Circulating DCs migrated to the spleen, liver and lung but not lymph nodes. They also homed to the bone marrow, where they were retained better than in most other tissues. Homing of DCs to the bone marrow depended on constitutively expressed vascular cell adhesion molecule 1 and endothelial selectins in bone marrow microvessels. Two-photon intravital microscopy in bone marrow cavities showed that DCs formed stable antigen-dependent contacts with bone marrow - resident central memory T cells. Moreover, using this previously unknown migratory pathway, antigen-pulsed DCs were able to trigger central memory T cell - mediated recall responses in the bone marrow. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP von Andrian, UH (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. EM uva@cbr.med.harvard.edu RI Koni, Pandelakis/A-3349-2008; von Andrian, Ulrich/A-5775-2008; Bonasio, Roberto/P-1356-2014; OI Bonasio, Roberto/0000-0002-0767-0889; Weninger, Wolfgang/0000-0003-3133-8699 FU NHLBI NIH HHS [HL54936, HL62524, P01 HL056949, R01 HL054936, R01 HL062524, HL56949]; NIAID NIH HHS [AI061663, R01 AI061663] NR 50 TC 139 Z9 147 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2005 VL 6 IS 10 BP 1029 EP 1037 DI 10.1038/ni1249 PG 9 WC Immunology SC Immunology GA 966NR UT WOS:000232027200022 PM 16155571 ER PT J AU Colvin, RB Smith, RN AF Colvin, RB Smith, RN TI Antibody-mediated organ-allograft rejection SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CAPILLARY C4D DEPOSITION; CORONARY-ARTERY-DISEASE; INCOMPATIBLE CARBOHYDRATE ANTIGEN; DONOR KIDNEY-TRANSPLANTATION; ENDOTHELIAL-CELL ACTIVATION; MEMBRANE ATTACK COMPLEX; TISSUE FACTOR ACTIVITY; HUMORAL REJECTION; RENAL-ALLOGRAFTS; HLA ANTIBODIES AB Recent studies show that alloantibodies mediate a substantial proportion of graft-rejection episodes, contributing to both early and late graft loss. Rejection that is caused by antibody is mediated by different mechanisms from rejection that is caused by T cells, thereby requiring other approaches to treatment and prevention. Antibody induces rejection acutely through the fixation of complement, resulting in tissue injury and coagulation. In addition, complement activation recruits macrophages and neutrophils, causing additional endothelial injury. Antibody and complement also induce gene expression by endothelial cells, which is thought to remodel arteries and basement membranes, leading to fixed and irreversible anatomical lesions that permanently compromise graft function. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA 02140 USA. RP Colvin, RB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Warren 225, Cambridge, MA 02140 USA. EM colvin@helix.mgh.harvard.edu NR 122 TC 232 Z9 246 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD OCT PY 2005 VL 5 IS 10 BP 807 EP 817 DI 10.1038/nri1702 PG 11 WC Immunology SC Immunology GA 969JE UT WOS:000232229600016 PM 16175181 ER PT J AU Hemler, ME AF Hemler, ME TI Tetraspanin functions and associated microdomains SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID TRANSMEMBRANE 4 SUPERFAMILY; PROTEIN-KINASE-C; METASTASIS SUPPRESSOR KAI1/CD82; ALPHA 3 BETA-1-INTEGRIN; CELL-CELL ADHESION; LIPID RAFTS; TM4SF PROTEINS; GROWTH-FACTOR; PROLIFERATIVE RESPONSES; INTEGRIN ALPHA-6-BETA-4 AB Cell-surface proteins of the tetraspanin family are small, and often hidden by a canopy of tall glycoprotein neighbours in the cell membrane. Consequently, tetraspanins have been understudied and underappreciated, despite their presence on nearly all cell and tissue types. Important new genetic evidence has now emerged, and is bolstered by new insights into the cell biology, signalling and biochemistry of tetraspanins. These new findings provide a framework for better understanding of these mysterious molecules in the regulation of cellular processes, from signalling to motility. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Martin_Hemler@dfci.harvard.edu NR 120 TC 634 Z9 648 U1 3 U2 58 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD OCT PY 2005 VL 6 IS 10 BP 801 EP 811 DI 10.1038/nrm1736 PG 11 WC Cell Biology SC Cell Biology GA 973NG UT WOS:000232529200012 PM 16314869 ER PT J AU Zhang, JR Ma, ZF Treszezamsky, A Powell, SN AF Zhang, JR Ma, ZF Treszezamsky, A Powell, SN TI MDC1 interacts with Rad51 and facilitates homologous recombination SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID STRAND-BREAK REPAIR; DNA-DAMAGE CHECKPOINT; CELL-CYCLE; MAMMALIAN-CELLS; DIRECTED REPAIR; SIGNALING PATHWAYS; FHA DOMAIN; PROTEIN; BRCA1; PHOSPHORYLATION AB Mediator of DNA damage checkpoint protein-1 (MDC1) is a recently identified nuclear protein that participates in DNA-damage sensing and signaling. Here we report that knockdown of MDC1 by RNA interference results in cellular hypersensitivity to the DNA cross-linking agent mitomycin C and ionizing radiation and in impaired homology-mediated repair of double-strand breaks in DNA. MDC1 forms a complex with Rad51 through a direct interaction with the forkhead-associated domain of MDC1, not the BRCA1 C-terminal domain. Depletion of MDC1 results in impaired formation of Rad51 ionizing radiation-induced foci, reduced amounts of nuclear and chromatin-bound Rad51, and a corresponding increase in Rad51 protein degradation. Together, our findings suggest that MDC1 functions in Rad51-mediated homologous recombination by retaining Rad51 in chromatin. C1 Massachusetts Gen Hosp, MGH Canc Ctr, Dept Radiat Oncol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. RP Powell, SN (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, Dept Radiat Oncol, 149 13th St, Charlestown, MA 02129 USA. EM snpowell@radonc.wustl.edu FU NCI NIH HHS [CA107640] NR 39 TC 68 Z9 73 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD OCT PY 2005 VL 12 IS 10 BP 902 EP 909 DI 10.1038/nsmb991 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 971BJ UT WOS:000232355800017 PM 16186822 ER PT J AU Funovics, M Montet, X Reynolds, F Weissleder, R Josephson, L AF Funovics, M Montet, X Reynolds, F Weissleder, R Josephson, L TI Nanoparticles for the optical imaging of tumor E-selectin SO NEOPLASIA LA English DT Article DE nanoparticle; E-selectin; Lewis lung carcinoma; peptide; internalization ID IRON-OXIDE PARTICLES; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; ATHEROSCLEROTIC PLAQUES; ACTIVATED ENDOTHELIUM; ADHESION MOLECULES; PROSTATE-CANCER; CELL-ADHESION; PEPTIDE; LIVER; METASTASIS AB We designed a fluorescent peptide-magnetic nanoparticle conjugate that images E-selectin expression in mouse xenograft models of Lewis lung carcinoma (LLC) by fluorescence reflectance imaging. It was synthesized by attaching the E-selectin-binding peptide (ESBP; CDSDSDITWDOLWDLMK) to a CLIO(Cy5.5) nanoparticle to yield ESBP-CLIO(Cy5.5). Internalization by activated human umbilical vein endothelial cells (HUVECs) was rapid and mediated by E-selectin, indicated by the lack of uptake of nanoparticles bearing similar numbers of a scrambled peptide (Scram). To demonstrate the specificity of E-selectin targeting to ESBP-CLIO(Cy5.5) in vivo, we coinjected ESBP-CLIO (Cy5.5) and Scram-CLIO(Cy3.5) and demonstrated a high Cy5.5/Cy3.5 fluorescence ratio using the LLC. Histology showed that ESBP-CLIO was associated with tumor cells as well as endothelial cells, but fluorescence-activated cell sorter analysis showed a far less expression of E-selectin on LLC than on HUVECs. Using immunohistochemistry, we demonstrated E-selectin expression in both endothelial cells and cancer cells in human prostate cancer specimens. We conclude that ESBP-CLIO (Cy5.5) is a useful probe for imaging E-selectin associated with the LLC tumor, and that E-selectin is expressed not only on endothelial cells but also on LLC cells and human prostate cancer specimens. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Vienna Med Univ, Dept Angiog & Intervent Radiol, Vienna, Austria. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,5406, Charlestown, MA 02129 USA. EM ljosephson@partners.org OI Montet, Xavier/0000-0003-2442-5866 FU NIBIB NIH HHS [R01-EB00662] NR 41 TC 52 Z9 56 U1 0 U2 7 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 1522-8002 J9 NEOPLASIA JI Neoplasia PD OCT PY 2005 VL 7 IS 10 BP 904 EP 911 DI 10.1593/neo.05352 PG 8 WC Oncology SC Oncology GA 989MI UT WOS:000233677600003 PM 16242073 ER PT J AU Daffner, KR Ryan, KK Williams, DM Budson, AE Rentz, DM Scinto, LFM Holcomb, PJ AF Daffner, KR Ryan, KK Williams, DM Budson, AE Rentz, DM Scinto, LFM Holcomb, PJ TI Age-sensitivity of the P3 in cognitively high-performing adults: Unsettled issues SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID EVENT-RELATED POTENTIALS; NOVELTY; COMPONENT; STIMULI; ATTEND; TASKS C1 Brigham & Womens Hosp, Boston, MA 02115 USA. RP Daffner, KR (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kdaffner@partners.org NR 20 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2005 VL 26 IS 9 BP 1301 EP 1304 DI 10.1016/j.neurobiolaging.2005.05.026 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 974XG UT WOS:000232624100009 ER PT J AU Osipova, D Ahveninen, J Jensen, O Ylikoski, A Pekkonen, E AF Osipova, D Ahveninen, J Jensen, O Ylikoski, A Pekkonen, E TI Altered generation of spontaneous oscillations in Alzheimer's disease SO NEUROIMAGE LA English DT Article DE Alzheimer's disease; EEG; MEG; alpha activity; oscillatory sources ID HUMAN BRAIN; MAGNETOENCEPHALOGRAPHIC DATA; ALPHA RHYTHMS; EEG; DEMENTIA; COHERENCE; CSF AB Slowing of spontaneous alpha oscillations and an anterior shift of a source of alpha activity (8-13 Hz) have been consistently reported in the EEG studies of Alzheimer's disease (AD). It is unknown whether these changes are associated with a gradual shift in location and frequency of existing sources or rather with the involvement of a new set of oscillators. We addressed this question by applying source modeling (minimum current estimates, NICE) to spontaneous alpha activity recorded with a 306-channel MEG system from eleven non-medicated AD patients with mild to moderate cognitive impairment and twelve age-matched controls during the eyes-closed session. AD patients had predominant lower alpha band sources in the temporal regions, whereas in the controls, robust alpha sources were found near the parieto-occipital sulcus. Activation within the parieto-occipital region was significantly weaker, and activation in the right temporal area was significantly enhanced in the AD patients. These results suggest an increased temporal-lobe contribution coinciding with parieto-occipital deficits. We propose that NICE, which provides simultaneous mapping of several oscillatory sources, might be useful for detecting neurophysiological abnormalities associated with AD in combination with other neuropsychological and neurological measures. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Ctr Engn, BioMag Lab, FIN-00014 Helsinki, Finland. Helsinki Brain Res Ctr, Helsinki, Finland. Harvard Univ, MIT, Massachusetts Gen Hosp, Sch Med,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. FC Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands. Hosp Koskela, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. RP Osipova, D (reprint author), Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, POB 9, FIN-00014 Helsinki, Finland. EM darja.osipova@cbru.helsinki.fi RI Jensen, Ole/D-2120-2010; OI Pekkonen, Eero/0000-0003-1621-8752; Jensen, Ole/0000-0001-8193-8348 NR 34 TC 53 Z9 53 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2005 VL 27 IS 4 BP 835 EP 841 DI 10.1016/j.neuroimage.2005.05.011 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 968DD UT WOS:000232141200012 PM 15961323 ER PT J AU Culver, JP Siegel, AM Franceschini, MA Mandeville, JB Boas, DA AF Culver, JP Siegel, AM Franceschini, MA Mandeville, JB Boas, DA TI Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin SO NEUROIMAGE LA English DT Article DE hemodynamic contrasts; hemoglobin; diffuse optical tomography; diffuse optical imaging; near-infrared spectroscopy; deoxy-hemoglobin; total hemoglobin ID NEAR-INFRARED SPECTROSCOPY; DIFFUSE OPTICAL TOMOGRAPHY; RAT SOMATOSENSORY CORTEX; SPIN-ECHO BOLD; FOREPAW STIMULATION; OXYGENATION CHANGES; HEMODYNAMIC-RESPONSES; FUNCTIONAL ACTIVATION; INTRINSIC SIGNALS; NEURONAL-ACTIVITY AB With the aim of evaluating the relative performance of hemodynamic contrasts for mapping brain activity, the spatio-temporal response of oxy-, deoxy-, and total-hemoglobin concentrations were imaged with diffuse optical tomography during electrical stimulation of the rat somatosensory cortex. For both 6-s and 30-s stimulus durations, total hemoglobin images provided smaller activation areas than oxy- or deoxy-hemoglobin images. In addition, analysis of regions of interest near the sagittal sinus vein show significantly greater contrast in both oxy- and deoxy-relative to total hemoglobin, suggesting that oximetric contrasts have larger draining vein contributions compared to total hemoglobin contrasts under the given stimulus conditions. These results indicate that total hemoglobin and cerebral blood volume may have advantages as hemodynamic mapping contrasts, particularly for large amplitude, longer duration stimulus paradigms. (C) 2005 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Culver, JP (reprint author), Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, 4525 Scott Ave, St Louis, MO 63110 USA. EM culverj@wustl.edu FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [K25-NS44339, R29-NS38842] NR 83 TC 51 Z9 51 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2005 VL 27 IS 4 BP 947 EP 959 DI 10.1016/j.neuroimage.2005.05.052 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 968DD UT WOS:000232141200023 PM 16084112 ER PT J AU Kang, PB Krishnamoorthy, KS Shapiro, FD Darras, BT AF Kang, PB Krishnamoorthy, KS Shapiro, FD Darras, BT TI Asymmetrical presentations of spinal muscular atrophy type III (Kugelberg Welander disease) SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 10th International Congress of the World-Muscle-Society CY SEP 28-OCT 10, 2005 CL Iguassu Falls, BRAZIL SP World Muscle Soc C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2005 VL 15 IS 9-10 BP 724 EP 724 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 969GJ UT WOS:000232221900193 ER PT J AU Yehuda, R Bryant, R Marmar, C Zohar, J AF Yehuda, R Bryant, R Marmar, C Zohar, J TI Pathological responses to terrorism SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE terrorism; posttraumatic stress disorder; risk factors; biological studies; prospective studies ID POSTTRAUMATIC-STRESS-DISORDER; MOTOR-VEHICLE ACCIDENTS; 2-YEAR PROSPECTIVE EVALUATION; AUDITORY STARTLE RESPONSE; TRAUMATIC BRAIN-INJURY; ROAD TRAFFIC ACCIDENTS; DELAYED-ONSET PTSD; NEW-YORK-CITY; PERITRAUMATIC DISSOCIATION; PREDICTING PTSD AB Many important gains have been made in understanding PTSD and other responses to trauma as a result of neuroscience- based observations. Yet there are many gaps in our knowledge that currently impede our ability to predict those who will develop pathologic responses. Such knowledge is essential for developing appropriate strategies for mounting a mental health response in the aftermath of terrorism and for facilitating the recovery of individuals and society. This paper reviews clinical and biological studies that have led to an identification of pathologic responses following psychological trauma, including terrorism, and highlights areas of future-research. It is important to not only determine risk factors for the development of short-and long-term mental health responses to terrorism, but also apply these risk factors to the prediction of such responses on an individual level. It is also critical to consider the full spectrum of responses to terrorism, as well as the interplay between biological and psychological variables that contribute to these responses. Finally, it is essential to remove the barriers to collecting data in the aftermath of trauma by creating a culture of education in which the academic community can communicate to the public what is and is not known so that survivors of trauma and terrorism will understand the value of their participation in research to the generation of useful knowledge, and by maintaining the acquisition of knowledge as a priority for the government and those involved in the immediate delivery of services in the aftermath of large-scale disaster or trauma. C1 Bronx Vet Affairs Med Ctr, Psychiat OOMH, Bronx, NY 10468 USA. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, Psychiat OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov OI Bryant, Richard/0000-0002-9607-819X NR 89 TC 18 Z9 18 U1 11 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2005 VL 30 IS 10 BP 1793 EP 1805 DI 10.1038/sj.npp.1300816 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 965VJ UT WOS:000231978200003 PM 16012535 ER PT J AU Herbert, MR AF Herbert, MR TI Large brains in autism: The challenge of pervasive abnormality SO NEUROSCIENTIST LA English DT Review DE autism; macrocephaly; connectivity; neuroinflammation; complex processing; brain ID DEVELOPMENTAL LANGUAGE DISORDER; CENTRAL-NERVOUS-SYSTEM; HIGH-FUNCTIONING AUTISM; MATTER VOLUME INCREASE; CEREBRAL WHITE-MATTER; CORPUS-CALLOSUM SIZE; HEAD CIRCUMFERENCE; SPECTRUM DISORDER; ASPERGER-SYNDROME; INFANTILE-AUTISM AB The most replicated finding in autism neuroanatomy-a tendency to unusually large brains-has seemed paradoxical in relation to the specificity of the abnormalities in three behavioral domains that define autism. We now know a range of things about this phenomenon, including that brains in autism have a growth spurt shortly after birth and then slow in growth a few short years afterward, that only younger but not older brains are larger in autism than in controls, that white matter contributes disproportionately to this volume increase and in a nonuniform pattern suggesting postnatal pathology, that functional connectivity among regions of autistic brains is diminished, and that neuroinflammation (including microgliosis and astrogliosis) appears to be present in autistic brain tissue from childhood through adulthood. Alongside these pervasive brain tissue and functional abnormalities, there have arisen theories of pervasive or widespread neural information processing or signal coordination abnormalities (such as weak central coherence, impaired complex processing, and underconnectivity), which are argued to underlie the specific observable behavioral features of autism. This convergence of findings and models suggests that a systems- and chronic disease-based reformulation of function and pathophysiology in autism needs to be considered, and it opens the possibility for new treatment targets. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal, Charlestown, MA 02129 USA. RP Herbert, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal, 149 13th St,Room 6012, Charlestown, MA 02129 USA. EM mherbert1@partners.org NR 125 TC 100 Z9 103 U1 18 U2 25 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2005 VL 11 IS 5 BP 417 EP 440 DI 10.1177/0091270005278866 PG 24 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966VX UT WOS:000232052000010 PM 16151044 ER PT J AU Wines-Samuelson, M Shen, J AF Wines-Samuelson, M Shen, J TI Presenilins in the developing, adult, and aging cerebral cortex SO NEUROSCIENTIST LA English DT Review DE Alzheimer disease; frontal temporal dementia; neural progenitor cells; Cajal-Retzius neuron; synaptic plasticity; neuronal survival; notch; NMDA receptor; CREB; CBP; cortical lamination; synapse; neurodegeneration ID FAMILIAL ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; CAJAL-RETZIUS NEURONS; CELL FATE SPECIFICATION; LONG-TERM POTENTIATION; RADIAL GLIAL-CELLS; CAENORHABDITIS-ELEGANS; SYNAPTIC PLASTICITY; TRANSGENIC MICE AB Mutations in presenilins are the major cause of familial Alzheimer disease. The involvement of presenilins in the pathogenesis of Alzheimer disease, therefore, has been the subject of intense investigation during the past decade. Genetic analysis of phenotypes associated with presenilin mutations in invertebrate and vertebrate systems has greatly advanced our understanding of the in vivo functions of presenilins. In this review, the authors will summarize the current understanding of presenilin function, with an emphasis on the mammalian cerebral cortex. During development, presenilins play crucial roles in the maintenance of neural progenitor cell proliferation, the temporal control of neuronal differentiation, the survival of Cajal-Retzius neurons, and proper neuronal migration in the developing cerebral cortex. Analysis of presenilin function in the adult cerebral cortex has revealed essential roles for presenilins in synaptic plasticity, long-term memory, and neuronal survival. The authors will also discuss the molecular mechanisms through which presenilins may mediate these functions, including the Notch, CREB, and NMDA receptor-mediated signaling pathways. These diverse functions of presenilins in cortical development and function and neuronal survival have important implications for the pathogenesis of neurodegenerative dementia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurol Dis,Program Neurosci, Boston, MA 02115 USA. RP Shen, J (reprint author), Harvard Univ, Sch Med, Ctr Neurol Dis, New Res Bldg 636E,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM jshen@rics.bwh.harvard.edu FU NINDS NIH HHS [NS42818, NS41783] NR 96 TC 44 Z9 48 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2005 VL 11 IS 5 BP 441 EP 451 DI 10.1177/1073858405278922 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966VX UT WOS:000232052000011 PM 16151045 ER PT J AU Rajadhyaksha, AM Kosofsky, BE AF Rajadhyaksha, AM Kosofsky, BE TI Psychostimulants, L-type calcium channels, kinases, and phosphatases SO NEUROSCIENTIST LA English DT Review DE drug addiction; Ca(v)1.2; Ca(v)1.3; ventral tegmental area; nucleus accumbens; striatum; phosphorylation ID VENTRAL TEGMENTAL AREA; DEPENDENT PROTEIN-KINASE; PDZ DOMAIN PROTEIN; CA2+ CHANNELS; BEHAVIORAL SENSITIZATION; SYNAPTIC PLASTICITY; CREB PHOSPHORYLATION; NUCLEUS-ACCUMBENS; GENE-EXPRESSION; CLASS-C AB There is growing evidence for the role of voltage-gated L-type Ca2+ channels in mediating aspects of the addictive properties of psychostimulants. L-type Ca2+ channels activate Ca2+ second-messenger pathways that regulate protein phosphorylation and thereby activation of target gene expression. Here the authors will review recent progress in our understanding of L-type Ca2+ channel-activated signal transduction pathways that contribute to molecular neuroadaptations evident following acute and chronic exposures to psychostimulants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol & Dev Neurosci Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. RP Rajadhyaksha, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol & Dev Neurosci Lab, Room 2415,CNY2, Charlestown, MA 02129 USA. EM rajadhan@helix.mgh.harvard.edu FU NIDA NIH HHS [K01 DA014057, K01 DA014057-05] NR 62 TC 20 Z9 20 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2005 VL 11 IS 5 BP 494 EP 502 DI 10.1177/1073858405278236 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966VX UT WOS:000232052000015 PM 16151049 ER PT J AU D'Ambrosio, AL Williams, SC Lignelli, A Salchow, DJ Spicer, G Libien, J Chin, SS Liebsch, NJ Kazim, M Bruce, JN Connolly, ES AF D'Ambrosio, AL Williams, SC Lignelli, A Salchow, DJ Spicer, G Libien, J Chin, SS Liebsch, NJ Kazim, M Bruce, JN Connolly, ES TI Clinicopathological review: Giant cell reparative granuloma of the orbit SO NEUROSURGERY LA English DT Review DE giant cell; granuloma; orbit; radiation therapy; surgery ID TEMPORAL BONE; ETHMOID SINUS; SKULL BASE; TUMOR; LESIONS; PROPTOSIS; SKELETON C1 Columbia Univ, Coll Phys & Surg, Dept Neurol Surg, New York, NY 10032 USA. New York Presbyterian Hosp, New York, NY USA. Columbia Univ, Dept Neurosurg, New York, NY 10032 USA. Columbia Univ, Dept Radiol, New York, NY 10032 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP D'Ambrosio, AL (reprint author), Columbia Univ, Coll Phys & Surg, Dept Neurol Surg, 710 W 168th St, New York, NY 10032 USA. EM ad504@columbia.edu NR 32 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2005 VL 57 IS 4 BP 773 EP 777 DI 10.1227/01.NEU.0000181346.81156.69 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 031CK UT WOS:000236681500046 PM 16239891 ER PT J AU Flaherty, AW Williams, ZM Amirnovin, R Kasper, E Rauch, SL Cosgrove, GR Eskandar, EN AF Flaherty, Alice W. Williams, Ziv M. Amirnovin, Ramin Kasper, Ekkehard Rauch, Scott L. Cosgrove, G. Rees Eskandar, Emad N. TI DEEP BRAIN STIMULATION OF THE ANTERIOR INTERNAL CAPSULE FOR THE TREATMENT OF TOURETTE SYNDROME: TECHNICAL CASE REPORT SO NEUROSURGERY LA English DT Article DE Deep brain stimulation; Internal capsule; Obsessive-compulsive disorder; Tourette syndrome; Ventral striatum AB OBJECTIVE AND IMPORTANCE: Medical treatment of Tourette syndrome is often ineffective or is accompanied by debilitating side effects, therefore prompting the need to evaluate surgical therapies. CLINICAL PRESENTATION: We present the case of a 37-year-old woman with severe Tourette syndrome since the age of 10 years. Her symptoms included frequent vocalizations and severe head and arm jerks that resulted in unilateral blindness. Trials of more than 40 medications and other therapies had failed to relieve the tics. INTERVENTION: We implanted bilateral electrodes in the anterior limb of the internal capsule, terminating in the vicinity of the nucleus accumbens. At 18-month follow-up, optimal stimulation continued to lower her tic frequency and severity significantly. CONCLUSION: Our findings suggest that stimulation of the anterior internal capsule may be a safe and effective procedure for the treatment of Tourette syndrome. C1 [Williams, Ziv M.; Amirnovin, Ramin; Kasper, Ekkehard; Cosgrove, G. Rees; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, Boston, MA 02114 USA. [Flaherty, Alice W.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Rauch, Scott L.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, 15 Parkman St,ACC 331, Boston, MA 02114 USA. EM eeskandar@partners.org FU Medtronic, Inc. FX SLR is engaged in research supported in part by Medtronic, Inc. NR 10 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2005 VL 57 IS 4 SU 4 AR ONS403 DI 10.1227/01.NEU.0000176854.24694.95 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA V21LL UT WOS:000208209000057 ER PT J AU Buckley, TC Kamholz, BW Mozley, SL Gulliver, SB Holohan, DR Helstrom, AW Walsh, K Morissette, SB Kassel, JD AF Buckley, TC Kamholz, BW Mozley, SL Gulliver, SB Holohan, DR Helstrom, AW Walsh, K Morissette, SB Kassel, JD TI A psychometric evaluation of the Smoking Consequences Questionnaire-Adult in smokers with psychiatric conditions SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID OUTCOME EXPECTANCIES; NICOTINE DEPENDENCE; PREVALENCE; CESSATION; VALIDITY; ALCOHOL AB Rates of smoking among individuals with psychiatric conditions are much greater than those seen in the general population, yet little is known about the psychometric properties of commonly used instruments that assess smoking-related variables among smokers with psychiatric conditions. The present study examined the factor structure and psychometric characteristics of the Smoking Consequences Questionnaire-Adult (SCQ-A; Copeland, Brandon, & Quinn, 1995, Psychological Assessment, 7, 484-494) among smokers with psychiatric conditions. A confirmatory factor analysis of the instrument indicated that the factor structure derived by the instrument's authors provided an adequate fit to the data. In addition, many of the 10 subscales of the SCQ-A demonstrated adequate internal consistency as assessed by Cronbach's alpha as well as adequate test-retest reliability over the course of I week. Based on the data derived from this sample, the SCQ-A has adequate psychometric properties for applications involving smokers with psychiatric conditions. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02131 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. VA Med Ctr, Salem, VA USA. Univ Illinois, Chicago, IL USA. RP Buckley, TC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02131 USA. EM todd.buckley@med.va.gov FU NIDA NIH HHS [DA16138, DA16273, DA15113] NR 20 TC 32 Z9 33 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD OCT PY 2005 VL 7 IS 5 BP 739 EP 745 DI 10.1080/14622200500259788 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 982CD UT WOS:000233134600005 PM 16191745 ER PT J AU Soteriades, ES Hauser, R Kawachi, I Liarokapis, D Christiani, DC Kales, SN AF Soteriades, ES Hauser, R Kawachi, I Liarokapis, D Christiani, DC Kales, SN TI Obesity and cardiovascular disease risk factors in firefighters: A prospective cohort study SO OBESITY RESEARCH LA English DT Article DE BMI; fitness; clustering; weight; cardiovascular disease ID BODY-MASS INDEX; UNITED-STATES; PHYSICAL-FITNESS; FIRE FIGHTERS; ECONOMIC COST; HEALTH-STATUS; US ADULTS; FOLLOW-UP; OVERWEIGHT; MORTALITY AB Objective: Obesity, despite being a significant determinant of fitness for duty, is reaching epidemic levels in the work-place. Firefighters' fitness is important to their health and to public safety. Research Methods and Procedures: We examined the distribution of BMI and its association with major cardiovascular disease (CVD) risk factors in Massachusetts firefighters who underwent baseline (1996) and annual medical examinations through a statewide medical surveillance program over 5 years of follow-up. We also evaluated firefighters' weight change over time. Results: The mean BMI among 332 firefighters increased from 29 at baseline to 30 at the follow-up examination (2001), and the prevalence of obesity increased from 35% to 40%, respectively (p < 0.0001). In addition, the proportion of firefighters with extreme obesity increased 4-fold at follow-up (from 0.6% to 2.4%, p < 0.0001). Obese firefighters were more likely to have hypertension (p = 0.03) and low high-density lipoprotein-cholesterol (p = 0.01) at follow-up. Firefighters with extreme obesity had an average of 2.1 CVD risk factors (excluding obesity) in contrast to 1.5 CVD risk factors for normal-weight firefighters (p = 0.02). Finally, on average, normal-weight firefighters gained 1.1 pounds, whereas firefighters with BMI >= 35 gained 1.9 pounds per year of active duty over 5 years of follow-up. Discussion: Obesity is a major concern among firefighters and shows worsening trends over time. Periodic medical evaluations coupled with exercise and dietary guidelines are needed to address this problem, which threatens firefighters' health and may jeopardize public safety. C1 Cambridge Hosp, Dept Med Employee & Ind Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Inst Educ Technol, Epirus, Greece. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02115 USA. RP Kales, SN (reprint author), Cambridge Hosp, Dept Med Employee & Ind Med, 1493 Cambridge St, Cambridge, MA 02139 USA. EM skales@challiance.org FU NIOSH CDC HHS [OH03729] NR 44 TC 58 Z9 59 U1 0 U2 9 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 OCT PY 2005 VL 13 IS 10 BP 1756 EP 1763 DI 10.1038/oby.2005.214 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 987GS UT WOS:000233507000013 PM 16286523 ER PT J AU Wexler, DJ Hu, FB Manson, JE Rifai, N Meigs, JB AF Wexler, DJ Hu, FB Manson, JE Rifai, N Meigs, JB TI Mediating effects of inflammatory biomarkers on insulin resistance associated with obesity SO OBESITY RESEARCH LA English DT Article DE type 2 diabetes; insulin resistance; endothelial dysfunction; inflammation; body composition ID NECROSIS-FACTOR-ALPHA; DEPENDENT DIABETES-MELLITUS; C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; SUBCUTANEOUS ADIPOSE-TISSUE; BODY-MASS INDEX; ANTHROPOMETRIC MEASUREMENTS; WAIST CIRCUMFERENCE; PHYSICAL-ACTIVITY; ABDOMINAL FAT AB Objective: Obesity is associated with elevated levels of biomarkers of inflammation and endothelial dysfunction [including C-reactive protein (CRP), E-selectin, and intercellular adhesion molecule-1], as well as insulin resistance (IR) and type 2 diabetes. We tested the hypothesis that these biomarkers mediate associations among obesity, IR, and risk of diabetes. Research Methods and Procedures: We stratified 5 10 initially non-diabetic women in the Nurses' Health Study cohort into four phenotypes above/below median BMI (27 kg/m(2)) and waist circumference (81 cm): low BMI-low waist (LBLW; N = 190), low BMI-high waist (LBHW; N = 74), high BMI-low waist (HBLW; N = 27), and high BMI-high waist (HBHW; N = 219). Results: In models assessing associations of weight phenotype with IR [fasting insulin (FI)], adjusted for age and diabetes risk factors, mean FI was higher comparing HBHW women (13.6 mu U/mL, p < 0.0001) and LBHW (11.5 mu U/mL, p = 0.02) with LBLW women (8.6 mu U/mL); HBLW and LBLW women were not significantly different. Differences in FI levels were most strongly attenuated after adjustment for E-selectin comparing LBHW with LBLW women (11.7 vs. 9.7 mu U/mL, p = 0.2). Discussion: In logistic regression models, LBHW predicted diabetes (risk factor-adjusted relative risk 2.06, 1.05 to 6.40), compared with LBLW, but was no longer significant after adjustment for E-selectin or CRP. After adjusting for CRP and E-selectin, only HBHW and E-selectin were significantly associated with risk of diabetes. In women with central adiposity and low BMI, endothelial dysfunction and inflammation may mediate the relationship among central fat, IR, and incident diabetes. C1 Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, 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. Childrens Hosp, Med Ctr, Dept Pathol, 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, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845, DK46519, DK36798] NR 65 TC 17 Z9 17 U1 0 U2 0 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 OCT PY 2005 VL 13 IS 10 BP 1772 EP 1783 DI 10.1038/oby.2005.216 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 987GS UT WOS:000233507000015 PM 16286525 ER PT J AU Tsai, AG Glick, HA Shera, D Stern, L Samaha, FF AF Tsai, AG Glick, HA Shera, D Stern, L Samaha, FF TI Cost-effectiveness of a low-carbohydrate diet and a standard diet in severe obesity SO OBESITY RESEARCH LA English DT Article; Proceedings Paper CT 10th Annual National Research Service Award Trainees Research Conference CY JUN 05, 2004 CL San Diego, CA ID LOW-FAT DIET; WEIGHT-LOSS; RANDOMIZED-TRIAL; FOLLOW-UP; LIFE; INTERVENTION; REDUCTION; METFORMIN; ADULTS; CARE AB Objective: Low-carbohydrate diets have become a popular alternative to standard diets for weight loss. Our aim was to compare the cost-effectiveness of these two diets. Research Methods and Procedures: The patient population included 129 severely obese subjects (BMI = 42.9) from a randomized trial; participants had a high prevalence of diabetes or metabolic syndrome. We compared within-trial costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (CER) for the two study groups. We imputed missing values for QALYs. The CER was bootstrapped to derive 95% confidence intervals and to define acceptability cut-offs. We took a societal perspective for our analysis. Results: Total costs during the one year of the trial were $6742 +/- 6675 and $6249 +/- 5100 for the low-carbohydrate and standard groups, respectively (p = 0.78). Participants experienced 0.64 +/- 0.02 and 0.61 +/- 0.02 QALYs during the one year of the study, respectively (p = 0.17 for difference). The point estimate of the incremental CER was $-1225/QALY (i.e., the low-carbohydrate diet dominated the standard diet). However, in the bootstrap analysis, the wide spread of CERs caused the 95% confidence interval to be undefined. The probabilities that the low-carbohydrate diet was acceptable, using cut-offs of $50,000/QALY, $100,000/QALY, and $150,000/QALY, were 72.4% 78.6%, and 79.8%, respectively. Discussion: The low-carbohydrate diet was not more cost-effective for weight loss than the Standard diet in the patient population studied. Larger studies are needed to better assess the cost-effectiveness of dietary therapies for weight loss. C1 Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Div Cardiovasc, Dept Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Biostat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Tsai, AG (reprint author), Univ Penn, Weight & Eating Disorders Program, 3535 Market St,3rd Floor, Philadelphia, PA 19104 USA. EM gildena@mail.med.upenn.edu FU PHS HHS [2-T32-HP-010026] NR 32 TC 13 Z9 13 U1 1 U2 6 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 OCT PY 2005 VL 13 IS 10 BP 1834 EP 1840 DI 10.1038/oby.2005.223 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 987GS UT WOS:000233507000022 PM 16286532 ER PT J AU Yu, EN Meniconi, ME Tufail, F Baltatzis, S Foster, CS Christen, WG AF Yu, EN Meniconi, ME Tufail, F Baltatzis, S Foster, CS Christen, WG TI Outcomes of treatment with immunomodulatory therapy in patients with corticosteroid-resistant juvenile idiopathic arthritis-associated chronic iridocyclitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE immunomodulatory therapy; iridocyclitis; juvenile idiopathic arthritis; uveitis ID RHEUMATOID-ARTHRITIS; METHOTREXATE THERAPY; OCULAR COMPLICATIONS; CONTROLLED TRIAL; CHRONIC UVEITIS; DOUBLE-BLIND; EPIDEMIOLOGY; CHILDHOOD; SEVERITY; EFFICACY AB Purpose: To describe the clinical outcome of patients with juvenile idiopathic arthritis (JIA)-associated chronic iridocyclitis unresponsive to conventional therapy, in whom inflammation was eventually controlled using immunomodulatory therapy (IMT), and to determine if patients treated early with IMT have better visual acuity outcomes than those treated with corticosteroid alone. Methods: Patients with JIA-associated chronic iridocyclitis receiving immunomodulatory therapy at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary between 1981 and 2001 were studied. Inclusion criteria: JIA with chronic corticosteroid-dependent uveitis; IMT for a minimum of one year; minimum follow-up of three years; inflammation eventually controlled for a minimum of six consecutive months by IMT. Results: At last visit, 51% of eyes (23 eyes) had acuity of 20/20 to 20/40, 16% (7 eyes) had 20/50 to 20/100, and 33% (15 eyes) had 20/200 or less. In patients whose chronic inflammation was eventually controlled within three years from onset of the uveitis, final bilateral vision was maintained within 20/20 to 20/30, except for a patient whose one eye had poor vision at initial consultation. When acuities at the end of the follow-up period of patients treated early with IMT were compared with acuities at the initial consultation of patients treated late with IMT, with duration of uveitis matched for each patient, visual acuities of those treated early were statistically significantly better than those treated late with IMT ( p < 0.005 right and left eyes pooled; p = 0.0075 best eyes; p = 0.0375 worst eyes). Conclusions: We noted improvement or maintenance of visual acuity (86%) during the course of follow-up of patients with treatment-resistant JIA-associated uveitis treated with effective IMT. However, only IMT given early in the disease course was noted to be associated with bilateral visual acuity of 20/30 or better. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. RP Foster, CS (reprint author), Massachusetts Eye Res & Surg Inst, 5 Cambridge Ctr,8th Floor, Cambridge, MA 02142 USA. EM fosters@uveitis.org NR 27 TC 19 Z9 19 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD OCT PY 2005 VL 13 IS 5 BP 353 EP 360 DI 10.1080/09273940590951061 PG 8 WC Ophthalmology SC Ophthalmology GA 972ZE UT WOS:000232491600003 PM 16419420 ER PT J AU Daoud, YJ Foster, CS Ahmed, AR AF Daoud, YJ Foster, CS Ahmed, AR TI Eyelid skin involvement in pemphigus foliaceus SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE eyelids; pemphigus foliaceus; intravenous immunoglobulin (IVIg) therapy; desmoglein 1 ID INTRAVENOUS IMMUNOGLOBULIN THERAPY; MUCOCUTANEOUS BLISTERING DISEASES; VULGARIS ANTIGENS; AUTOIMMUNE; DESMOGLEIN-1; EXPRESSION; NOSE AB Purpose: To report the involvement of eyelid skin in a patient with pemphigus foliaceus. Methods: Retrospective, interventional case report of a patient with pemphigus foliaceus involving both eyelids. The diagnosis of pemphigus foliaceus was based on histopathology and confirmed by direct immunofluorescence and immunoblot. Failure to respond to conventional immunosuppressive therapy, including high-dose corticosteroids, methotrexate, azathioprine, dapsone, and mycophenolate mofetil, necessitated the use of intravenous immunoglobulin (IVIg) therapy. Results: After successful treatment with IVIg, no change in visual acuity or other sequelae secondary to ocular pemphigus foliaceus were observed. Normal ocular architecture was maintained. Clinical remission was observed after successful therapy. Conclusions : Pemphigus foliaceus involves the skin of the eyelid and does not involve the conjunctiva. The patient did not respond to conventional immunosuppressive therapy. The use of IVIg as mono-therapy resulted in long-term clinical remission. C1 Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA USA. New England Baptist Hosp, Dept Med, Ctr Blistering Dis, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med, 188 Longwood Ave, Boston, MA 02115 USA. EM Razzaque_Ahmed@hsdm.harvard.edu NR 14 TC 6 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD OCT PY 2005 VL 13 IS 5 BP 389 EP 394 DI 10.1080/09273940590951025 PG 6 WC Ophthalmology SC Ophthalmology GA 972ZE UT WOS:000232491600008 PM 16419424 ER PT J AU Balaram, M Rashid, S Dana, R AF Balaram, M Rashid, S Dana, R TI Chronic ocular surface disease after allogeneic bone marrow transplantation SO OCULAR SURFACE LA English DT Article DE allogeneic bone marrow transplantation; graft-versus-host disease; ocular surface disease ID VERSUS-HOST-DISEASE; DRY EYE SYNDROME; KERATOCONJUNCTIVITIS SICCA; CELL TRANSPLANTATION; FUNCTIONAL STATUS; GRAFT; MANIFESTATIONS; SURVIVORS; CYCLOSPORINE; PROPHYLAXIS AB Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation (allo-BMT). Ocular surface disease (OSD) is one of the most common manifestations of chronic ocular GVHD, yet little is known about it. In this article, we review the available literature on this condition and present results from our study of the manifestations of OSD in the chronic phase (> 3 months duration) post allo-BMT. Our study consisted of a retrospective chart review of 62 allo-BMT patients with chronic OSD evaluated at our center between 1995 and 2002. The clinical features, systemic associations, treatment, and status of OSD at the last follow-up are presented and discussed in the context of other reports of OSD in GVHD. C1 Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu NR 38 TC 22 Z9 22 U1 0 U2 1 PU ETHIS COMMUNICATINS, INC PI NEW YORK PA 75 MAIDEN LANE, STE 408, NEW YORK, NY 10038 USA SN 1542-0124 J9 OCUL SURF JI Ocul. Surf. PD OCT PY 2005 VL 3 IS 4 BP 203 EP 210 PG 8 WC Ophthalmology SC Ophthalmology GA 974JV UT WOS:000232588600005 PM 17131029 ER PT J AU Dana, R AF Dana, R TI Corneal antigen presentation: Molecular regulation and functional implications SO OCULAR SURFACE LA English DT Article; Proceedings Paper CT Cullen Symposium on Corneal and Ocular Surface Inflammation CY JAN 21-22, 2005 CL Cullen Eye Inst Baylor Coll Med, Houston, TX HO Cullen Eye Inst Baylor Coll Med DE corneal antigen; inflammatory response ID DRAINING LYMPH-NODES; DENDRITIC CELLS; TRANSPLANTATION; SURVIVAL; LYMPHANGIOGENESIS; ALLOIMMUNITY; IMMUNOLOGY; EXPRESSION; REJECTION; HOSTS AB Presentation of corneal antigens for induction of adaptive immune responses is mediated by corneal antigen-presenting cells (APC), including those that infiltrate the cornea in response to inflammatory stimuli and, to a lesser extent, those that reside in the cornea and up-regulate activation markers in response to inflammation. Significant progress has been made in the last decade in dissecting the molecular mechanisms that mediate APC infiltration into the cornea. However, it has recently been determined that exit of APC out of the cornea is critical for induction of T cells that normally reside outside of the cornea in lymphoid reservoirs. Much less is understood about the molecular regulation of APC egress from the cornea, but our laboratory has recently discovered that APC access to afferent lymphatics and draining lymph nodes requires signaling mediated by VEGFR-3. We describe herein the functional implication of APC trafficking and the prospects for novel immunomodulatory strategies based on regulating APC migration. C1 Harvard Univ, Schepens Eye Res Inst, Dept Ophthalmol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cambridge, MA 02138 USA. RP Dana, R (reprint author), 20 Stanford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu NR 19 TC 9 Z9 9 U1 0 U2 0 PU ETHIS COMMUNICATINS, INC PI NEW YORK PA 75 MAIDEN LANE, STE 408, NEW YORK, NY 10038 USA SN 1542-0124 J9 OCUL SURF JI Ocul. Surf. PD OCT PY 2005 VL 3 IS 4 SU S BP S169 EP S172 PG 4 WC Ophthalmology SC Ophthalmology GA 975PD UT WOS:000232673500011 PM 17216112 ER PT J AU Penson, RT Seiden, MV AF Penson, RT Seiden, MV TI Topotecan: Weighing in when there are many options SO ONCOLOGIST LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; EPITHELIAL OVARIAN-CANCER; PHASE-II; CISPLATIN; RECURRENT; CARBOPLATIN; DOXORUBICIN; PACLITAXEL; MANAGEMENT; THERAPY AB The manuscript by Armstrong et al. in this issue of The Oncologist, reviewing the toxicity and efficacy of full-dose topotecan delivered as second-line therapy in individuals with small cell lung cancer or ovarian cancer, will likely serve as both the most comprehensive and the final review of this active agent delivered at the U.S. Food and Drug Administration-approved dosage and schedule. The review represents large, relatively homogeneous patient populations with prior platinum exposure and convincingly describes topotecan as an agent with activity that is comparable with those of all other approved drugs in this setting and a well-defined and relatively circumscribed set of toxicities. While the activity of topotecan in small cell carcinoma provides individuals with the hope for further palliation at the time of tumor recurrence, as discussed by Dr. Markman in this issue, the best use of this agent in the management of recurrent ovarian cancer is far from clear because, in part, of a growing list of approved active agents, most notably liposomal doxorubicin, gemcitabine, and weekly paclitaxel; a return to platinum; or a host of other agents such as vinorelbine, altretamine, irinotecan, docetaxel, etoposide, and others. The most pressing need is to accept that palliative therapies are designed to palliate and improve symptoms, and to move away from end points of radiologic and marker response to a focus on "clinical benefit" and clinically more meaningful end points. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Yawkey 9066,55 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 13 TC 2 Z9 2 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD OCT PY 2005 VL 10 IS 9 BP 698 EP 700 DI 10.1634/theoncologist.10-9-698 PG 3 WC Oncology SC Oncology GA 980DS UT WOS:000232994800004 PM 16249349 ER PT J AU Ligibel, J Winer, E AF Ligibel, J Winer, E TI Adjuvant hormonal therapy in early breast cancer - The Kumar/Leonard article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID RANDOMIZED-TRIAL; CYCLOPHOSPHAMIDE; FLUOROURACIL; METHOTREXATE; TAMOXIFEN; GOSERELIN; ABLATION C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Ligibel, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 11 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 OCT PY 2005 VL 19 IS 11 BP 1441 EP + PG 3 WC Oncology SC Oncology GA 052ER UT WOS:000238214800008 ER PT J AU Masciari, S Garber, JE AF Masciari, S Garber, JE TI Evaluation and management of women with BRCA1/2 mutations - The Peshkin/Isaacs article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID CONTRALATERAL BREAST-CANCER; BASAL EPITHELIAL PHENOTYPE; CARRIERS; RISK C1 Dana Farber Canc Inst, Canc Risk & Prevent Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 11 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 OCT PY 2005 VL 19 IS 11 BP 1468 EP + PG 2 WC Oncology SC Oncology GA 052ER UT WOS:000238214800012 ER PT J AU Pirl, WF AF Pirl, WF TI Psychiatric assessment and symptom management in elderly cancer patients - The Winell/Roth article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc, Psychiat Oncol Serv, Boston, MA 02114 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Psychiat Oncol Serv, Boston, MA 02114 USA. NR 3 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 OCT PY 2005 VL 19 IS 11 BP 1490 EP + PG 2 WC Oncology SC Oncology GA 052ER UT WOS:000238214800015 ER PT J AU Cremers, SL Lora, AN Ferrufino-Ponce, ZK AF Cremers, SL Lora, AN Ferrufino-Ponce, ZK TI Global Rating Assessment of Skills in Intraocular Surgery (GRASIS) SO OPHTHALMOLOGY LA English DT Article ID OBJECTIVE STRUCTURED ASSESSMENT; TECHNICAL SKILLS; OPHTHALMOLOGY RESIDENTS; SURGICAL COMPETENCE; LENS IMPLANTATION; CATARACT-SURGERY; AMERICAN BOARD; VITREOUS LOSS; PHACOEMULSIFICATION; EDUCATION AB Objective: The American Board of Ophthalmology in conjunction with the Accreditation Council for Graduate Medical Education has mandated the systematic assessment of surgical competence of ophthalmology residents at all residency programs. We present a tool complementary to the Objective Assessment of Skills in Intraocular Surgery (OASIS) to assess residents' surgical competence. Participants: Twenty experts in resident education, including the chiefs of all ophthalmology services and the chief resident at the Harvard Medical School Department of Ophthalmology. Methods: A 1-page subjective evaluation form was developed in conjunction with the Objective Assessment of Skills in Intraocular Surgery evaluation form to assess the surgical skills of residents. A panel of surgeons at the Harvard Medical School Department of Ophthalmology at the Massachusetts Eye and Ear Infirmary reviewed the form and provided constructive feedback. Results: Experts' comments were incorporated, establishing face and content validity. Conclusions: The Global Rating Assessment of Skills in Intraocular Surgery (GRASIS) has face and content validity. It can be used to assess a resident's surgical care of patients as well as a resident's surgical knowledge, preparedness, and interpersonal skills. Reliability and predictive validity will be determined at our institution. We believe the GRASIS evaluation form will be a valuable tool in conjunction with the OASIS evaluation form for assessing ophthalmology residents' surgical skills at other residency programs as well. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Comprehens Ophthalmol Serv, Boston, MA 02114 USA. Georgetown Univ, Sch Med, Washington, DC USA. RP Cremers, SL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Comprehens Ophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. EM Sandra_Cremers@meei.harvard.edu NR 25 TC 50 Z9 50 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2005 VL 112 IS 10 BP 1655 EP 1660 DI 10.1016/j.ophtha.2005.05.010 PG 6 WC Ophthalmology SC Ophthalmology GA 970IS UT WOS:000232299200003 PM 16102834 ER PT J AU Park, BH Pierce, MC Cense, B de Boer, JF AF Park, BH Pierce, MC Cense, B de Boer, JF TI Optic axis determination accuracy for fiber-based polarization-sensitive optical coherence tomography SO OPTICS LETTERS LA English DT Article ID RESOLVED MUELLER MATRIX; BIOLOGICAL TISSUE; BIREFRINGENCE; ORIENTATION; LIGHT; LAYER AB We present a generalized analysis of fiber-based polarization-sensitive optical coherence tomography with an emphasis on determination of sample optic axis orientation. The polarization properties of a fiber-based system can cause an overall rotation in a Poincare sphere representation such that the plane of possible measured sample optic axes for linear birefringence and diattenuation no longer lies in the QU-plane. The optic axis orientation can be recovered as an angle on this rotated plane, subject to an offset and overall indeterminacy in sign such that only the magnitude, but not the direction, of a change in orientation can be determined. We discuss the accuracy of optic axis determination due to a fundamental limit on the accuracy with which a polarization state can be determined as a function of signal-to-noise ratio. (c) 2005 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Park, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 50 Blossom St,BAR 7, Boston, MA 02114 USA. EM hylepark@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCRR NIH HHS [R01-RR019768] NR 25 TC 28 Z9 28 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 1 PY 2005 VL 30 IS 19 BP 2587 EP 2589 DI 10.1364/OL.30.002587 PG 3 WC Optics SC Optics GA 966UE UT WOS:000232046700021 PM 16208908 ER PT J AU Yun, SH AF Yun, SH TI Mode locking of a wavelength-swept laser SO OPTICS LETTERS LA English DT Article ID FREQUENCY-DOMAIN REFLECTOMETRY; FIBER LASER; SHIFTED FEEDBACK; FILTER AB Self-starting, stable mode-locked pulses can be generated from a wavelength-swept laser through the interplay between an intracavity scanning filter and self-phase modulation. From an Er3+-doped fiber laser employing a scanning Fabry-Perot filter, 100 ps optical pulses are obtained at a 12-MHz repetition rate with center wavelengths that are swept over 27 nm around 1.55 mu m in 1 ms. (c) 2005 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 718, Boston, MA 02114 USA. EM syun@hms.harvard.edu NR 12 TC 5 Z9 5 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 1 PY 2005 VL 30 IS 19 BP 2660 EP 2662 DI 10.1364/OL.30.002660 PG 3 WC Optics SC Optics GA 966UE UT WOS:000232046700046 PM 16208933 ER PT J AU Foschi, F Cavrini, F Montebugnoli, L Stashenko, P Sambri, V Prati, C AF Foschi, F Cavrini, F Montebugnoli, L Stashenko, P Sambri, V Prati, C TI Detection of bacteria in endodontic samples by polymerase chain reaction assays and association with defined clinical signs in Italian patients SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE clinical signs; endodontic pathogens; Enterococcus faecalis; polymerase chain reaction; Treponema denticola ID INFECTED ROOT CANALS; PORPHYROMONAS-GINGIVALIS; BACTEROIDES-FORSYTHUS; TREPONEMA-DENTICOLA; PERIAPICAL LESIONS; MOLECULAR-DETECTION; FILLED TEETH; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ANTIMICROBIAL SUSCEPTIBILITY; ANAEROBIC-BACTERIA AB Background/aims: The presence of selected bacteria (Enterococcus faecalis, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis, Treponema denticola) in infected root canals was studied using polymerase chain reaction (PCR) assays, and the association of bacteria with clinical signs of endodontic disease was assessed. The null hypothesis, that no difference could be observed between clinical signs of apical periodontitis and a specific bacterial strain, was tested. Methods: Microbial samples were obtained from 62 teeth in 54 patients with endodontic disease. For each tooth, clinical data including patient symptoms were collected. Teeth were categorized by diagnosis as having acute apical periodontitis (AAP, teeth with clinical symptoms but no periapical radiolucency, n = 22), chronic apical periodontitis (CAP, teeth with radiolucency but no clinical symptoms, n = 15) or exacerbated apical periodontitis (EAP, teeth with symptoms and radiolucency, n = 25). Seventy-one percent of cases were primary endodontic infections, and 29% were recurrent ('secondary') endodontic infections (failing cases). PCR assays were used to detect the presence of the selected bacteria. Results: T. denticola and E. faecalis were each detected in 15 of 62 samples (24%), P. gingivalis in 8 samples (13%), P. intermedia in 5 samples (8%), and T. forsythensis in 4 samples (7%). T. denticola was detected in 56% of teeth with EAP. E. faecalis was found in 60% of teeth with CAP and in 72% of teeth with secondary infection. Statistical analysis demonstrated an association of CAP and secondary endodontic infection with the presence of E. faecalis. (P < 0.01). EAP was associated with the presence of T. denticola (P < 0.01). Conclusion: T. denticola was associated with symptomatic endodontic disease in the presence of apical bone resorption. E. faecalis was associated with treatment failures. We suggest that these species may play critical roles in endodontic pathology. C1 Univ Bologna, Dept Dent Sci, Endodont Unit, I-40125 Bologna, Italy. Univ Bologna, Alma Mater Studiorum, Osped S Orsola, DMCSS,Sect Microbiol, Bologna, Italy. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Ctr Riferimento Reg Emilia Romagna Emergenza Micr, CRREM, Bologna, Italy. RP Foschi, F (reprint author), Univ Bologna, Dept Dent Sci, Endodont Unit, Via San Vitale 59, I-40125 Bologna, Italy. EM foschi@alma.unibo.it RI Foschi, Federico /E-7531-2012; OI Prati, Carlo/0000-0001-8163-8628 FU NIDCR NIH HHS [DE-11664] NR 55 TC 57 Z9 59 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD OCT PY 2005 VL 20 IS 5 BP 289 EP 295 DI 10.1111/j.1399-302X.2005.00227.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 954JS UT WOS:000231152000005 PM 16101964 ER PT J AU Ung, F Sindwani, R Metson, R AF Ung, F Sindwani, R Metson, R TI Endoscopic frontal sinus obliteration: A new technique for the treatment of chronic frontal sinusitis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 108th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 19-22, 2004 CL New York, NY SP Amer Acad Otolaryngol Head & Neck Surg ID SURGERY; OPERATIONS AB OBJECTIVES: Patients who fail endoscopic drainage procedures for chronic frontal sinusitis often require obliteration of the frontal sinus with abdominal fat. The purpose of this study was to evaluate an endoscopic technique for frontal sinus obliteration. STUDY DESIGN AND SETTING: Retrospective case-control. Thirty-five patients underwent frontal sinus obliteration using either an endoscopic (n=10) or conventional osteoplastic flap (n=25) technique from 1994 to 2004 at an academic medical center. RESULTS: Patients undergoing endoscopic obliteration had less blood loss (P = 0.006), decreased operative time (P = 0.016), and a shorter hospital stay (P = 0.003) compared to osteoplastic control subjects. All 3 surgical complications occurred in the control group. No patients required additional surgery for frontal sinusitis. CONCLUSIONS: The endoscopic approach to frontal sinus obliteration appears to reduce patient morbidity and should be considered in the surgical management of advanced frontal sinus disease. SIGNIFICANCE: This is the first report of a minimally-invasive technique for frontal sinus obliteration. (C) 2005 American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. St Louis Univ, Dept Otolaryngol, St Louis, MO 63103 USA. RP Metson, R (reprint author), 0 Emerson Pl, Boston, MA 02114 USA. EM ralph_metson@meei.harvard.edu NR 13 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2005 VL 133 IS 4 BP 551 EP 555 DI 10.1016/j.otohns.2005.06.014 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 972NR UT WOS:000232461000014 PM 16213928 ER PT J AU Young, MRI Lathers, DMR AF Young, MRI Lathers, DMR TI Combination docetaxel plus vitamin D-3 as an immune therapy in animals bearing squamous cell carcinomas SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID CD34(+) PROGENITOR CELLS; NECK-CANCER PATIENTS; PERIPHERAL-BLOOD; DENDRITIC CELLS; BREAST-CANCER; HEAD; DIFFERENTIATION; LYMPHOCYTES; SUPPRESSION; PROLIFERATION AB OBJECTIVE: Background tumor growth results in the mobilization of immune inhibitory CD34(+) progenitor cells. However, vitamin D, can differentiate the CD34(+) cells into immune stimulatory dendritic cells. This study determined if docetaxel treatment could increase the impact of the vitamin D, to generate dendritic cells. METHODS: The murine squamous cell carcinoma model, SCC VII/SF, which is often used as a head and neck cancer model, was used to determine the immunological effects of two cycles of docetaxel plus vitamin D,. RESULTS: Vitamin D, with or without docetaxel was similarly effective in reducing CD34(+) cell levels within the spleen, lymph nodes, and tumor. Dendritic cell levels were similarly enhanced in the lymph nodes by vitamin D, alone or combined with docetaxel. However, the combination treatment caused a prominent increase in intratumoral levels of active T cells, which was not observed by the individual treatments. CONCLUSION: Incorporating docetaxel treatment with vitamin D-3 differentiation-inducing treatment enhances intratumoral immune responsiveness. (C) 2005 American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. All rights reserved. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Res Serv 151, Dept Res Serv, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Res Serv 151, Dept Res Serv, 109 Bee St, Charleston, SC 29401 USA. EM rita.young@med.va.gov FU NCI NIH HHS [CA97813, CA85266] NR 21 TC 4 Z9 4 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2005 VL 133 IS 4 BP 611 EP 618 DI 10.1016/j.otohns.2005.05.658 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 972NR UT WOS:000232461000024 PM 16213938 ER PT J AU Cohen, DM AF Cohen, DM TI TRPV4 and the mammalian kidney SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review ID RECEPTOR POTENTIAL VANILLOID-4; HEAT-EVOKED ACTIVATION; CELL-VOLUME REGULATION; CATION CHANNEL TRPV4; ASCITES TUMOR-CELLS; TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE A(2); ION-CHANNEL; SRC KINASE; PROTEIN AB Transient receptor potential vanilloid 4 (TRPV4) was identified as the mammalian homologue of the Caenorhabditis elegans osmosensory channel protein, OSM-9. In mammals, TRPV4 is activated by a variety of stimuli including thermal stress, fatty acid metabolites, and hypotonicity. Two distinct mechanisms have been described through which TRPV4 may be activated by hypotonicity: one involves the Src family of nonreceptor protein tyrosine kinases, whereas a second is mediated via arachidonic acid metabolites. TRPV4 likely plays a role in systemic osmoregulation; accordingly, it is expressed in the blood-brain barrier-deficient osmosensory nuclei of the hypothalamus. TRPV4 is also abundantly expressed in the kidney, and its precisely demarcated distribution along the kidney tubule permits speculation about a physiological role in this tissue. TRPV4-expressing and TRPV4-negative tubule segments co-exist at all levels of the kidney, from the cortex through the inner medulla. It is conceivable that basolaterally expressed TRPV4 transmits signals arising in the interstitium (e.g, changing tonicity) to more-distal tubule segments where "fine-tuning" of the incipient urine takes place. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, 3314 SW US Vet Hosp Rd,Mailcode PP262, Portland, OR 97239 USA. EM cohend@ohsu.edu NR 54 TC 37 Z9 41 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 2005 VL 451 IS 1 BP 168 EP 175 DI 10.1007/s00424-005-1456-9 PG 8 WC Physiology SC Physiology GA 971GS UT WOS:000232372800020 PM 15988590 ER PT J AU O'Neil, RG Heller, S AF O'Neil, RG Heller, S TI The mechanosensitive nature of TRPV channels SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE TRPV channels; mechanosensory; osmosensory; touch; hearing; shear stress; pressure; calcium ID POLYCYSTIC KIDNEY-DISEASE; AORTIC BARORECEPTOR NEURONS; CORTICAL COLLECTING DUCT; HEAT-EVOKED ACTIVATION; CAENORHABDITIS-ELEGANS; ION CHANNELS; ENDOTHELIAL-CELLS; CATION CHANNEL; INSECT MECHANORECEPTOR; TRANSDUCTION CHANNEL AB Transient receptor potential vanilloid (TRPV) channels are widely expressed in both sensory and nonsensory cells. Whereas the channels display a broad diversity to activation by chemical and physical stimuli, activation by mechanical stimuli is common to many members of this group in both lower and higher organisms. Genetic screening in Caenorhabditis elegans has demonstrated an essential role for two TRPV channels in sensory neurons. OSM-9 and OCR-2, for example, are essential for both osmosensory and mechanosensory (nose-touch) behaviors. Likewise, two Drosophila TRPV channels, NAN and IAV, have been shown to be critical for hearing by the mechanosensitive chordotonal organs located in the fly's antennae. The mechanosensitive nature of the channels appears to be conserved in higher organisms for some TRPV channels. Two vertebrate channels, TRPV2 and TRPV4, are sensitive to hypotonic cell swelling, shear stress/fluid flow (TRPV4), and membrane stretch (TRPV2). In the osmosensing neurons of the hypothalamus (circumventricular organs), TRPV4 appears to function as an osmoreceptor, or part of an osmoreceptor complex, in control of vasopressin release, whereas in inner ear hair cells and vascular baroreceptors a mechanosensory role is suggestive, but not demonstrated. Finally, in many nonsensory cells expressing TRPV4, such as vascular endothelial cells and renal tubular epithelial cells, the channel exhibits well-developed local mechanosensory transduction processes where both cell swelling and shear stress/fluid flow lead to channel activation. Hence, many TRPV channels, or combinations of TRPV channels, display a mechanosensitive nature that underlies multiple mechanosensitive processes from worms to mammals. C1 Univ Texas, Hlth Sci Ctr, Sch Med, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP O'Neil, RG (reprint author), Univ Texas, Hlth Sci Ctr, Sch Med, Dept Integrat Biol & Pharmacol, 6431 Fannin St, Houston, TX 77030 USA. EM roger.g.oneil@uth.tmc.edu RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 96 TC 170 Z9 188 U1 1 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 2005 VL 451 IS 1 BP 193 EP 203 DI 10.1007/s00424-005-1424-4 PG 11 WC Physiology SC Physiology GA 971GS UT WOS:000232372800023 PM 15909178 ER PT J AU Montalbetti, N Li, Q Gonzalez-Perrett, S Semprine, J Chen, XZ Cantiello, HF AF Montalbetti, N Li, Q Gonzalez-Perrett, S Semprine, J Chen, XZ Cantiello, HF TI Effect of hydro-osmotic pressure on polycystin-2 channel function in the human syncytiotrophoblast SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE polycystin-2; TRP channels; non-selective cation channels; Ca(2+) channels; placenta; osmotic pressure; gel swelling equilibrium ID KIDNEY-DISEASE PROTEINS; SMOOTH-MUSCLE-CELLS; CATION CHANNEL; PRIMARY CILIUM; INACTIVATION; PKD2; MECHANOSENSATION; TISSUE; VILLI; ADPKD AB Polycystin-2 (PC2), one of the gene products whose mutations cause autosomal dominant polycystic kidney disease is a transient receptor potential (TRP)type (TRPP2) Ca(2+)- permeable, non-selective cation channel. PC2 is localized in the plasma membrane, the primary cilium, and other cellular organelles of renal epithelial and other cells. Recent studies indicate that PC2 is involved in signal transduction events associated with the transient increase in cytosolic Ca(2+). Proof of evidence now hinges on involvement of the PC2 channel in the transduction of environmental signals. PC2 is abundantly expressed in the apical membrane of human syncytiotrophoblast (hST), a highly intricate epithelial tissue, which is essential for the maternal - fetal transfer of solutes, including ions. Physical forces such as hydrostatic ( H) and osmotic ( P) pressure play important roles in placenta homeostasis. In this study, we provide new information on PC2 channel regulation in the hST by these environmental factors, and propose a model as to how they may trigger the activation of PC2. Using apical hST vesicles reconstituted in a lipid bilayer system, we found that a change in either H or P modified PC2 channel activity. This stimulatory effect was no longer observed in hST vesicles pre-treated with the actin cytoskeleton disrupter cytochalasin D. As shown by immunofluorescence analysis PC2 co-localized with actin. laments in the vicinity of the plasma membrane. This co-localization was disrupted by cytochalasin D. Taken together, our findings indicate that physical forces exerted on cells regulate PC2 channel activity by a sensory mechanism involving the actin cytoskeleton. C1 Massachusetts Gen Hosp East, Renal Unit, Charlestown, MA 02129 USA. Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisicoquim & Quim Analit, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Univ Alberta, Dept Physiol, Edmonton, AB T6G 2E1, Canada. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp East, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu OI Montalbetti, Nicolas/0000-0003-2897-9540 NR 37 TC 28 Z9 29 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 2005 VL 451 IS 1 BP 294 EP 303 DI 10.1007/s00424-005-1458-7 PG 10 WC Physiology SC Physiology GA 971GS UT WOS:000232372800034 PM 16025301 ER PT J AU Cantiello, HF Montalbetti, N Goldmann, WH Raychowdhury, MK Gonzalez-Perrett, S Timpanaro, GA Chasan, B AF Cantiello, HF Montalbetti, N Goldmann, WH Raychowdhury, MK Gonzalez-Perrett, S Timpanaro, GA Chasan, B TI Cation channel activity of mucolipin-1: the effect of calcium SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE mucolipidosis type IV; mucolipin-1; Trp channels; TrpML1; non-selective cation channel; polycystin-2; atomic force microscopy; pH regulation ID CAENORHABDITIS-ELEGANS; ABNORMAL TRANSPORT; LYSOSOMAL PATHWAY; MEMBRANE-PROTEIN; POTENTIAL ROLE; K+ CHANNELS; IV; GENE; PH; IDENTIFICATION AB Mucolipidosis type IV (MLIV) is a rare, neurogenetic disorder characterized by developmental abnormalities of the brain, and impaired neurological, ophthalmological, and gastric function. Considered a lysosomal disease, MLIV is characterized by the accumulation of large vacuoles in various cell types. Recent evidence indicates that MLIV is caused by mutations in MCOLN1, the gene that encodes mucolipin-1 (ML1), a 65-kDa protein showing sequence homology and topological similarities with polycystin-2 and other transient receptor potential (TRP) channels. In this report, our observations on the channel properties of ML1, and molecular pathophysiology of MLIV are reviewed and expanded. Our studies have shown that ML1 is a multiple sub-conductance, non-selective cation channel. MLIV-causing mutations result in functional differences in the channel protein. In particular, the V446L and Delta F408 mutations retain channel function but have interesting functional differences with regards to pH dependence and Ca2+ transport. While the wild-type protein is inhibited by Ca2+ transport, mutant ML1 is not. Atomic force microscopy imaging of ML1 channels shows that changes in pH modify the aggregation and size of the ML1 channels, which has an impact on vesicular fusogenesis. The new evidence provides support for a novel role of ML1 cation channels in vesicular acidification and normal endosomal function. C1 Massachusetts Gen Hosp East, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisicoquim & Quim Analit, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Boston Univ, Dept Phys, Boston, MA 02215 USA. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp East, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu RI Goldmann, Wolfgang/H-5572-2013; OI Montalbetti, Nicolas/0000-0003-2897-9540 NR 48 TC 42 Z9 42 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 2005 VL 451 IS 1 BP 304 EP 312 DI 10.1007/s00424-005-1448-9 PG 9 WC Physiology SC Physiology GA 971GS UT WOS:000232372800035 PM 16133264 ER PT J AU Saxon, AJ McCarty, D AF Saxon, AJ McCarty, D TI Challenges in the adoption of new pharmacotherapeutics for addiction to alcohol and other drugs SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE buprenorphine; pharmacotherapy; adoption of innovations ID COCAINE-DEPENDENT OUTPATIENTS; PLACEBO-CONTROLLED TRIAL; FOLLOW-UP OUTCOMES; UNITED-STATES; METHADONE-MAINTENANCE; COST-EFFECTIVENESS; SUBSTANCE-ABUSE; NARCOTIC ADDICTION; FIELD EXPERIENCE; OPIATE ADDICTION AB The adoption of pharmacotherapies for the treatment of alcohol and drug use disorders has progressed slowly despite the approval of new and effective medications. This paper begins with overviews of the prevalence of alcohol and drug abuse and dependence, the costs of addiction to the nation, and the value of treatment services. The role of pharmacotherapy in the treatment of addictive diseases is examined, and factors that affect the adoption and use of medications for alcohol and drug treatment are identified and discussed. Investigations that tested the effectiveness of buprenorphine for treatment of opioid dependence in new settings illustrate physician and counselor training and mentorship strategies that may promote the adoption of medications in the treatment of alcohol and drug use disorders. The paper concludes with a discussion of barriers and ways to surmount the barriers and to foster greater use of medications in alcohol and drug treatment. (c) 2005 Published by Elsevier Inc. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. RP Saxon, AJ (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM andrew.saxon@med.va.gov NR 77 TC 34 Z9 34 U1 7 U2 10 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 OCT PY 2005 VL 108 IS 1 BP 119 EP 128 DI 10.1016/j.pharmthera.2005.06.014 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 974KB UT WOS:000232589200010 PM 16055196 ER PT J AU John, TE Hallisey, RK AF John, TE Hallisey, RK TI Argatroban and lepirudin requirements in a 6-year-old patient with heparin-induced thrombocytopenia SO PHARMACOTHERAPY LA English DT Article DE argatroban; lepirudin; heparin-induced thrombocytopenia; pediatric ID PEDIATRIC-PATIENTS; DRUG DISPOSITION; THERAPY; CHILDHOOD; CHILDREN; ACETAMINOPHEN; MATURATION; DIAGNOSIS; INFANCY; ADULTS AB A 6-year-old girl required argatroban at dosages up to 18 mu g/kg/minute for treatment of heparin-induced thrombocytopenia (HIT) type 2; however, her activated partial thromboplastin time (aPTT) values remained subtherapeutic. Treatment was converted to lepirudin, which resulted in therapeutic aPTT values, and later to long-term warfarin therapy; no further thromboembolic incidents occurred. The reporting of cases of HIT in prepubertal patients has generally been scarce. Argatroban and lepirudin dosing and pharmacokinetics have not yet been established for young children. The argatroban dosage for this patient exceeded the upper limit of the dose range for adults. Several possible explanations for why argatroban did not illustrate typical first-order pharmacokinetics in this patient are discussed, and the pharmacokinetics and pharmacodynamics of argatroban are compared with those of lepirudin, with special consideration given to the pediatric population. C1 Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. RP John, TE (reprint author), Massachusetts Gen Hosp, Dept Pharm, Room GRB 005,55 Fruit St, Boston, MA 02114 USA. EM tjohn@partners.org NR 33 TC 2 Z9 2 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 OCT PY 2005 VL 25 IS 10 BP 1383 EP 1388 DI 10.1592/phco.2005.25.10.1383 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 971BP UT WOS:000232356400013 PM 16185183 ER PT J AU McMaster, NL Tschirhart, SAJ Erwin, TC Linn, WD AF McMaster, NL Tschirhart, SAJ Erwin, TC Linn, WD TI Modifiable coronary heart disease risk factors: quality of care in an academic VA geriatrics clinic. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 23-26, 2005 CL San Francisco, CA SP Amer Coll Clin Pharmacy C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 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 OCT PY 2005 VL 25 IS 10 BP 1449 EP 1450 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 971BP UT WOS:000232356400087 ER PT J AU Castro, M Molina-Paris, C Deisboeck, TS AF Castro, M Molina-Paris, C Deisboeck, TS TI Tumor growth instability and the onset of invasion SO PHYSICAL REVIEW E LA English DT Article ID IMMUNE SYSTEM COMPETITION; MULTICELLULAR SPHEROIDS; THEORETICAL-ANALYSIS; CAPILLARY FORMATION; FACTOR EXPRESSION; CELL MOTILITY; HUMAN GLIOMAS; FIELD MODEL; IN-VITRO; ANGIOGENESIS AB Motivated by experimental observations, we develop a mathematical model of chemotactically directed tumor growth. We present an analytical study of the model as well as a numerical one. The mathematical analysis shows that: (i) tumor cell proliferation by itself cannot generate the invasive branching behavior observed experimentally, (ii) heterotype chemotaxis provides an instability mechanism that leads to the onset of tumor invasion, and (iii) homotype chemotaxis does not provide such an instability mechanism but enhances the mean speed of the tumor surface. The numerical results not only support the assumptions needed to perform the mathematical analysis but they also provide evidence of (i), (ii), and (iii). Finally, both the analytical study and the numerical work agree with the experimental phenomena. C1 Univ Pontif Comillas, ICAI, GISC, E-28015 Madrid, Spain. Univ Pontif Comillas, ICAI, DNL, E-28015 Madrid, Spain. Univ San Pablo, Fac Farm, Dept Matemat Fis Aplicada & Fis Quim, E-28660 Madrid, Spain. Univ Leeds, Dept Appl Math, Leeds LS2 9JT, W Yorkshire, England. Massachusetts Gen Hosp, Harvard MIT HST, Athinoula A Martinos Ctr Biomed Imaging, Complex Biosyst Modeling Lab, Charlestown, MA 02129 USA. RP Castro, M (reprint author), Univ Pontif Comillas, ICAI, GISC, E-28015 Madrid, Spain. RI Castro, Mario/A-3585-2009 OI Castro, Mario/0000-0003-3288-6144 FU NCI NIH HHS [CA 113004, CA 085139] NR 54 TC 13 Z9 14 U1 0 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD OCT PY 2005 VL 72 IS 4 AR 041907 DI 10.1103/PhysRevE.72.041907 PN 1 PG 12 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 979GO UT WOS:000232930600070 PM 16383420 ER PT J AU Frand, AR Russel, S Ruvkun, G AF Frand, AR Russel, S Ruvkun, G TI Functional genomic analysis of C-elegans molting SO PLOS BIOLOGY LA English DT Article ID ECDYSIS-TRIGGERING HORMONE; NEMATODE CAENORHABDITIS-ELEGANS; ANGIOTENSIN-CONVERTING ENZYME; BONE MORPHOGENETIC PROTEIN-1; SECRETORY-EXCRETORY SYSTEM; MESSENGER-RNA; EXTRACELLULAR-MATRIX; LARVAL DEVELOPMENT; POSITIVE-FEEDBACK; ECLOSION HORMONE AB Although the molting cycle is a hallmark of insects and nematodes, neither the endocrine control of molting via size, stage, and nutritional inputs nor the enzymatic mechanism for synthesis and release of the exoskeleton is well understood. Here, we identify endocrine and enzymatic regulators of molting in C. elegans through a genome-wide RNA-interference screen. Products of the 159 genes discovered include annotated transcription factors, secreted peptides, transmembrane proteins, and extracellular matrix enzymes essential for molting. Fusions between several genes and green fluorescent protein show a pulse of expression before each molt in epithelial cells that synthesize the exoskeleton, indicating that the corresponding proteins are made in the correct time and place to regulate molting. We show further that inactivation of particular genes abrogates expression of the green fluorescent protein reporter genes, revealing regulatory networks that might couple the expression of genes essential for molting to endocrine cues. Many molting genes are conserved in parasitic nematodes responsible for human disease, and thus represent attractive targets for pesticide and pharmaceutical development. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK070147] NR 86 TC 146 Z9 153 U1 3 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD OCT PY 2005 VL 3 IS 10 BP 1719 EP 1733 AR e312 DI 10.1371/journal.pbio.0030312 PG 15 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 971SJ UT WOS:000232404600007 PM 16122351 ER PT J AU Gressmann, H Linz, B Ghai, R Pleissner, KP Schlapbach, R Yamaoka, Y Kraft, C Suerbaum, S Meyer, TF Achtman, M AF Gressmann, H Linz, B Ghai, R Pleissner, KP Schlapbach, R Yamaoka, Y Kraft, C Suerbaum, S Meyer, TF Achtman, M TI Gain and loss of multiple genes during the evolution of Helicobacter pylori SO PLOS GENETICS LA English DT Article ID COMPLETE GENOME SEQUENCE; GASTRIC EPITHELIAL-CELLS; MYCOBACTERIUM-TUBERCULOSIS; YERSINIA-PESTIS; IV SECRETION; HUMAN HOST; DIVERSITY; STRAINS; CAGA; RECOMBINATION AB Sequence diversity and gene content distinguish most isolates of Helicobacter pylori. Even greater sequence differences differentiate distinct populations of H. pylori from different continents, but it was not clear whether these populations also differ in gene content. To address this question, we tested 56 globally representative strains of H. pylori and four strains of Helicobacter acinonychis with whole genome microarrays. Of the weighted average of 1,531 genes present in the two sequenced genomes, 25% are absent in at least one strain of H. pylori and 21% were absent or variable in H. acinonychis. We extrapolate that the core genome present in all isolates of H. pylori contains 11,1111 genes. Variable genes tend to be small and possess unusual GC content; many of them have probably been imported by horizontal gene transfer. Phylogenetic trees based on the microarray data differ from those based on sequences of seven genes from the core genome. These discrepancies are due to homoplasies resulting from independent gene loss by deletion or recombination in multiple strains, which distort phylogenetic patterns. The patterns of these discrepancies versus population structure allow a reconstruction of the timing of the acquisition of variable genes within this species. Variable genes that are located within the cog pathogenicity island were apparently first acquired en bloc after speciation. In contrast, most other variable genes are of unknown function or encode restriction/ modification enzymes, transposases, or outer membrane proteins. These seem to have been acquired prior to speciation of H. pylori and were subsequently lost by convergent evolution within individual strains. Thus, the use of microarrays can reveal patterns of gene gain or loss when examined within a phylogenetic context that is based on sequences of core genes. C1 Max Planck Inst Infektionsbiol, Dept Mol Biol, Berlin, Germany. Univ Giessen, Inst Med Microbiol, Giessen, Germany. Max Planck Inst Infektionsbiol, Core Facil Bioinformat, Berlin, Germany. Univ Zurich, ETH, Funct Genom Ctr, Zurich, Switzerland. ME DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Hannover Med Sch, Inst Med Mikrobiol & Krankenhaushyg, Hannover, Germany. RP Achtman, M (reprint author), Max Planck Inst Infektionsbiol, Dept Mol Biol, Berlin, Germany. EM achtman@mpiib-berlin.mpg.de RI Meyer, Thomas F./J-2485-2013; Ghai, Rohit/E-7086-2012; Schlapbach, Ralph/R-8234-2016 OI Meyer, Thomas F./0000-0002-6120-8679; NR 60 TC 132 Z9 137 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2005 VL 1 IS 4 BP 419 EP 428 AR e43 DI 10.1371/journal.pgen.0010043 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 003XE UT WOS:000234714800002 PM 16217547 ER PT J AU Ray, IB Heist, EK AF Ray, Indranill Basu Heist, E. Kevin TI Treating atrial fibrillation - What is the consensus now? SO POSTGRADUATE MEDICINE LA English DT Article AB Atrial fibrillation (AF) is a common cardiac arrhythmia, especially in elderly persons. Current recommendations outline pharmacologic and interventional therapies designed to minimize the risk of stroke and other morbidities that can accompany this condition. In this article, Drs Basu Ray and Heist review treatment options for cardioversion and control of rate and rhythm and make suggestions for best management in patients with chronic or intermittent AF. C1 Beth Israel Deaconess Med Ctr, Harvard Thorndike Electrophysiol Inst, Ctr Invas Cardiac Electrophysiol Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Ray, IB (reprint author), Beth Israel Deaconess Med Ctr, Harvard Thorndike Electrophysiol Inst, Ctr Invas Cardiac Electrophysiol Res, Room SL 418,330 Brookline Ave, Boston, MA 02215 USA. EM indranill_basuray@bidmc.harvard.edu RI Basu Ray, Indranill/D-3794-2011 NR 20 TC 3 Z9 3 U1 0 U2 2 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD OCT PY 2005 VL 118 IS 4 BP 47 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V44DP UT WOS:000202983700009 PM 16296263 ER PT J AU Montgomery, RB Bonham, M Nelson, PS Grim, J Makary, E Vessella, R Stahl, WL AF Montgomery, RB Bonham, M Nelson, PS Grim, J Makary, E Vessella, R Stahl, WL TI Estrogen effects on tubulin expression and taxane mediated cytotoxicity in prostate cancer cells SO PROSTATE LA English DT Article DE prostate cancer; tubulin; estrogen; paclitaxel; diethylstilbestrol ID ISOTYPE EXPRESSION; MICROTUBULE DYNAMICS; CARCINOMA-CELLS; PC-SPES; 2-METHOXYESTRADIOL; GROWTH; TAXOL; DIETHYLSTILBESTROL; POLYMERIZATION; CHEMOTHERAPY AB BACKGROUND. The present study was designed to determine if estrogens change microtubule polymerization and modulate cell cycle progression in vitro, related to modulation of tubulin expression and to determine if estrogens had antagonistic or synergistic effects with microtubule active agents. METHODS. cDNA array analysis of LNCaP cells treated with the estrogens, estradiol, estrone, diethylstilbestrol (DES), and 2-methoxyestradiol (2-ME) was carried out and the results confirmed by PCR and Western blotting. Microtubule arrays in cells treated with estrogens were assessed using indirect immunofluorescence. The effects of combining estrogens with taxane was assessed by MTT assay and flow cytometry for cell cycle kinetics. Human prostate cancer xenografts were treated with DES and docetaxel to assess the effects of combining estrogens and taxane in vivo. RESULTS. Treatment of LNCaP cells with DES and 2-ME suppressed transcripts and protein for beta-tubulin isotype lVa. This effect on tubulin synthesis was not blocked by estrogen or androgen receptor modulators. Other estrogens had no effect on beta-tubulin expression. 2-ME and DES decreased the density of microtubules. The administration of DES or 2-ME with paclitaxel enhanced cytotoxicity and G(2)-M arrest in vitro. DES enhanced tumor suppression in a human prostate cancer xenograft model when combined with the taxane docetaxel. CONCLUSION. The use of DES and 2-ME enhances the effects of taxanes and may be a novel and important means of increasing therapeutic efficacy of cytotoxic chemotherapy against prostate carcinoma. C1 VA Puget Sound HCS, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Oncol, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA USA. Univ Washington, Dept Physiol, Seattle, WA USA. Univ Washington, Dept Biophys, Seattle, WA USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. RP Montgomery, RB (reprint author), VA Puget Sound HCS, Mailstop 111ONC,1660 S Columbian Way, Seattle, WA 98108 USA. EM rbmontgo@u.washington.edu NR 34 TC 20 Z9 20 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD OCT 1 PY 2005 VL 65 IS 2 BP 141 EP 150 DI 10.1002/pros.20246 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 968DP UT WOS:000232142400006 PM 15924336 ER PT J AU Duan, XB Yarmush, D Berthiaume, F Jayaraman, A Yarmush, ML AF Duan, XB Yarmush, D Berthiaume, F Jayaraman, A Yarmush, ML TI Immunodepletion of albumin for two-dimensional gel detection of new mouse acute-phase protein and other plasma proteins SO PROTEOMICS LA English DT Article DE acute-phase proteins; albumin immunnodepletion; burn and infection; inter-alphatrypsin inhibitor heavy chain 4; mouse plasma 2-D gel map ID INTER-ALPHA-INHIBITOR; RAT SERUM; ACUTE-PANCREATITIS; HEAVY-CHAIN; INFLAMMATION; ELECTROPHORESIS; FAMILY; ALPHA-2-MACROGLOBULIN; RESPONSES; DISEASE AB immunodepletion of albumin to improve the 2-D gel resolution of human plasma proteins has recently been described. With the importance of mouse models in many studies in which serum or plasma is often analyzed, we have adopted this approach to immunoprecipitate mouse albumin and evaluated its effectiveness for 2-D separation of mouse plasma proteins. Purified polyclonal antibodies against mouse albumin were effective depleting intact albumin as well as its numerous fragments from mouse plasma samples. Removal of albumin resulted in better resolution of mouse plasma proteins. Three proteins, alpha(2)-macroglobulin, coagulation factor XII, and hemopexin, that were previously either undetectable or poorly resolved, were identified from albumin-depleted 2-D gels by peptide mass fingerprinting. Albumin depletion also led to partial loss of several other proteins such as clusterin and gelsolin. This loss can be attributed to the interaction with albumin itself because the specificity of the antibody was demonstrated by Western blot. When applying this method to the 2-D separation of plasma from inflamed mouse induced by cutaneous burn injury with superimposed Pseudomonas acruginosa infection, the upregulation of inter alpha-trypsin inhibitor heavy chain 4 (ITIH4) and hemopexin was unambiguously detected along with other mouse acute-phase proteins (APP), including haptoglobin and serum amyloid A. Based on the significant increase of ITIH4, we propose that this protein is a new member of mouse APP that are upregulated during the inflammatory response. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIGMS NIH HHS [5R01-GM-65474] NR 47 TC 26 Z9 27 U1 2 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD OCT PY 2005 VL 5 IS 15 BP 3991 EP 4000 DI 10.1002/pmic.200401257 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 978TN UT WOS:000232896000019 PM 16130172 ER PT J AU Beahrs, JO AF Beahrs, JO TI A social brain interpretation of psychotherapy SO PSYCHIATRIC ANNALS LA English DT Article; Proceedings Paper CT 155th Annual Meeting of the American-Psychiatric-Association CY MAY 18-23, 2002 CL PHILADELPHIA, PA SP Amer Psychiat Assoc ID MEMORY C1 Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Beahrs, JO (reprint author), 3318 NE Hancock St, Portland, OR 97212 USA. EM intarts@teleport.com NR 40 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 2005 VL 35 IS 10 BP 816 EP 822 PG 7 WC Psychiatry SC Psychiatry GA 974JC UT WOS:000232586600006 ER PT J AU Morrissey, JP Jackson, EW Ellis, AR Amaro, H Brown, VB Najavits, LM AF Morrissey, JP Jackson, EW Ellis, AR Amaro, H Brown, VB Najavits, LM TI Twelve-month outcomes of trauma-informed interventions for women with co-occurring disorders SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ADVERSE CHILDHOOD EXPERIENCES; SEVERE MENTAL-ILLNESS; SUBSTANCE-ABUSE; ALCOHOL-ABUSE; PROGRAM; HEALTH; SCHIZOPHRENIA; COMORBIDITY; DEPENDENCE AB Objective: Women with co-occurring mental health and substance use disorders frequently have a history of interpersonal violence, and past research has suggested that they are not served effectively by the current service system. The goal of the Women, Co-occurring Disorders, and Violence Study was to develop and test the effectiveness of new service approaches specifically designed for these women. Methods: A quasi-experimental treatment outcome study was conducted from 2001 to 2003 at nine sites. Although intervention specifics such as treatment length and modality varied across sites, each site used a comprehensive, integrated, trauma-informed, and consumer-involved approach to treatment. Substance use problem severity, mental health symptoms, and trauma symptoms were measured at baseline, and follow-up data were analyzed with prospective meta-analysis and hierarchical linear modeling. Results: A total of 2,026 women had data at the 12-month follow-up: 1,018 in the intervention group and 1,008 in the usual-care group. For substance use outcomes, no effect was found. The meta-analysis demonstrated small but statistically significant overall improvement in women's trauma and mental health symptoms in the intervention relative to the usual-care comparison condition. Analysis of key program elements demonstrated that integrating substance abuse, mental health, and trauma-related issues into counseling yielded greater improvement, whereas the delivery of numerous core services yielded less improvement relative to the comparison group. A few person-level characteristics were associated with increases or decreases in the intervention effect. These neither moderated nor supplanted the effects of integrated counseling. Conclusions: Outcomes for women with co-occurring disorders and a history of violence and trauma may improve with integrated treatment. C1 Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC 27599 USA. Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. Innovat Res & Training, Durham, NC USA. Northeastern Univ, Boston, MA 02115 USA. PROTOTYPES, Culver City, CA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dept Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Morrissey, JP (reprint author), Univ N Carolina, Dept Hlth Policy & Adm, 725 Martin Luther King Jr Blvd,Campus Box 7590, Chapel Hill, NC 27599 USA. EM joe_morrissey@unc.edu RI Amaro, Hortensia/G-8083-2011 FU CSAT SAMHSA HHS [TI-00-003] NR 40 TC 91 Z9 92 U1 4 U2 27 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2005 VL 56 IS 10 BP 1213 EP 1222 DI 10.1176/appi.ps.56.10.1213 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 972RE UT WOS:000232470100005 PM 16215186 ER PT J AU Roffman, JL Marci, CD Glick, DM Dougherty, DD Rauch, SL AF Roffman, JL Marci, CD Glick, DM Dougherty, DD Rauch, SL TI Neuroimaging and the functional neuroanatomy of psychotherapy SO PSYCHOLOGICAL MEDICINE LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; BRAIN METABOLIC-CHANGES; CEREBRAL-BLOOD-FLOW; COGNITIVE-BEHAVIORAL THERAPY; CONTROLLED CLINICAL-TRIALS; MAJOR DEPRESSION; SYMPTOM PROVOCATION; SPIDER PHOBIA; FEAR AB Background. Studies measuring the effects of psychotherapy on brain function are under-represented relative to analogous studies of medications, possibly reflecting historical biases. However, psychological constructs relevant to several modalities of psychotherapy have demonstrable neurobiological correlates, as indicated by functional neuroimaging studies in healthy subjects. This review examines initial attempts to measure directly the effects of psychotherapy on brain function in patients with depression or anxiety disorders. Method. Fourteen published, peer-reviewed functional neuroimaging investigations of psychotherapy were identified through a MEDLINE search and critically reviewed. Studies were compared for consistency of findings both within specific diagnostic categories, and between specific modalities of psychotherapy. Results were also compared to predicted neural models of psychotherapeutic interventions. Results. Behavioral therapy for anxiety disorders was consistently associated with attenuation of brain-imaging abnormalities in regions linked to the pathophysiology of anxiety, and with activation in regions related to positive reappraisal of anxiogenic stimuli. In studies of major depressive disorder, cognitive behavioral therapy and interpersonal therapy were associated with markedly similar changes in cortical-subcortical circuitry, but in unexpected directions. For any given psychiatric disorder, there was only partial overlap between the brain-imaging changes associated with pharmacotherapy and those associated with psychotherapy. Conclusions. Despite methodological limitations, initial neuroimaging Studies have revealed convergent and mechanistically sensible effects of psychotherapy on brain function across a range of psychiatric disorders. Further research in this area may take advantage of emerging neuroimaging techniques to explore a broader range of psychotherapies, with the ultimate goal of improving clinical decision-making and treatment. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jroffmann@partners.org NR 68 TC 102 Z9 104 U1 3 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2005 VL 35 IS 10 BP 1385 EP 1398 DI 10.1017/S0033291705005064 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 974JZ UT WOS:000232589000001 PM 16164763 ER PT J AU Lopez, MF Becker, HC AF Lopez, MF Becker, HC TI Effect of pattern and number of chronic ethanol exposures on subsequent voluntary ethanol intake in C57BL/6J mice SO PSYCHOPHARMACOLOGY LA English DT Article DE ethanol; withdrawal; self-administration; mice; relapse; limited access ID ALCOHOL-WITHDRAWAL; DEPENDENT RATS; ANIMAL-MODEL; DRINKING; DEPRIVATION; ALLOSTASIS; PREFERENCE; EPISODES; ANXIETY; ABSTINENCE AB Rationale: We previously demonstrated that chronic ethanol exposure and withdrawal experience significantly increased subsequent voluntary ethanol intake in C57BL/6J mice. This study was conducted to examine chronic ethanol conditions that optimize this enhanced ethanol-drinking behavior. Objectives: The purpose of this study was to examine whether the pattern and/or number of chronic ethanol exposures influence subsequent ethanol intake. Methods: C57BL/6J mice were trained to drink ethanol (15% v/v) in a limited access situation (2 h/day) until stable intake was achieved. In experiment 1, mice received two cycles of chronic ethanol exposure delivered either in an intermittent [multiple withdrawal (MW)] or continuous [continuous exposure (CE)] pattern. One week of daily drinking sessions followed each exposure. In experiment 2, mice received either two or four cycles of chronic intermittent ethanol exposure (MW), each followed by a week of testing sessions. Three additional weeks of ethanol intake testing followed the last ethanol (or air) exposure. Results: Experiment 1: Only the MW group evidenced a significant increase in ethanol intake compared to controls after the first chronic ethanol exposure. Both MW and CE groups consumed more ethanol than controls after the second ethanol-exposure period. Experiment 2: Ethanol intake in MW mice compared to controls significantly increased after two or four cycles of chronic ethanol exposure/withdrawal, and this heightened ethanol intake lasted longer in mice that received four cycles of chronic intermittent ethanol exposure. Conclusions: Increased voluntary ethanol intake after chronic ethanol exposure and withdrawal experience may be accelerated by intermittent (as opposed to continuous) ethanol exposure, and the effect may last longer with increased number of such experiences. C1 Med Univ S Carolina, Charles Alcohol Res Ctr, Ctr Drug & Alcohol Programs, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Lopez, MF (reprint author), Med Univ S Carolina, Charles Alcohol Res Ctr, Ctr Drug & Alcohol Programs, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. EM lopezm@musc.edu FU NIAAA NIH HHS [AA013885, AA014095, P50-AA10761] NR 41 TC 120 Z9 120 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2005 VL 181 IS 4 BP 688 EP 696 DI 10.1007/s00213-005-0026-3 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 975KL UT WOS:000232661300006 PM 16001125 ER PT J AU Thrall, JH AF Thrall, JH TI Reinventing radiology in the digital age Part II. New directions and new stakeholder value SO RADIOLOGY LA English DT Editorial Material ID TELERADIOLOGY; DUTY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM jthrall@partners.org NR 15 TC 16 Z9 16 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2005 VL 237 IS 1 BP 15 EP 18 DI 10.1148/radiol.2371050258 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 965RM UT WOS:000231968000005 PM 16183921 ER PT J AU Soto, JA Barish, MA Yee, J AF Soto, JA Barish, MA Yee, J TI Reader training in CT colonography: How much is enough? SO RADIOLOGY LA English DT Editorial Material ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; COLORECTAL NEOPLASIA; CONVENTIONAL COLONOSCOPY; POLYPS; PERFORMANCE C1 Boston Univ, Med Ctr, Dept Radiol, Boston, MA 02118 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. San Francisco Vet Adm Med Ctr, Dept Radiol, San Francisco, CA USA. RP Soto, JA (reprint author), Boston Univ, Med Ctr, Dept Radiol, 88 E Newton St, Boston, MA 02118 USA. EM jorge.Soto@bmc.org OI Soto, Jorge/0000-0003-2533-3015 NR 18 TC 35 Z9 37 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2005 VL 237 IS 1 BP 26 EP 27 DI 10.1148/radiol.2371050003 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 965RM UT WOS:000231968000007 PM 16183923 ER PT J AU Bluemke, DA Sahani, D Amendola, M Balzer, T Breuer, J Brown, JJ Casalino, DD Davis, PL Francis, IR Krinsky, G Lee, FT Lu, D Paulson, EK Schwartz, LH Siegelman, ES AF Bluemke, DA Sahani, D Amendola, M Balzer, T Breuer, J Brown, JJ Casalino, DD Davis, PL Francis, IR Krinsky, G Lee, FT Lu, D Paulson, EK Schwartz, LH Siegelman, ES TI Efficacy and safety of MR imaging with liver-specific contrast agent: US Multicenter Phase III study SO RADIOLOGY LA English DT Article ID GD-EOB-DTPA; HELICAL COMPUTED-TOMOGRAPHY; I CLINICAL-EVALUATION; ENHANCED MR; INTRAOPERATIVE ULTRASONOGRAPHY; HEPATOCELLULAR-CARCINOMA; PREOPERATIVE DETECTION; COLORECTAL-CANCER; GADOPENTETATE DIMEGLUMINE; HEPATIC-LESIONS AB PURPOSE: To assess prospectively the efficacy and safety of postcontrast magnetic resonance (MR) imaging with gadolinium,ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) compared with that of precontrast MR imaging in patients who are known to have or are suspected of having liver lesions and who are scheduled for hepatic surgery. MATERIALS AND METHODS: Investigational review board approval and written informed consent were obtained. HIPAA went into effect after data collection. A total of 172 patients were enrolled. After precontrast MR imaging, 169 patients (94 men, 75 women; mean age, 61 years; age range, 19-84 years) received an intravenous bolus of 25 mu mol/kg Gd-EOB-DTPA and Underwent dynamic gradient-recalled-echo and delayed MR imaging' 20 minutes after injection. Arterial and portal phase computed tomography (CT) were performed within 6 weeks of MR imaging. The standard of reference was surgery with intraoperative ultrasonography (US) and biopsy and/or pathologic evaluation of resected liver segments and/or 3-month follow-up of nonresected segments if intraoperative US was not available. Three blinded reviewers and unblinded site investigators identified liver lesions on segment maps. The Wilcoxon signed rank test was used to compare differences in per-patient sensitivity of precontrast, and postcontrast MR images. Adverse events were recorded, and patient monitoring and laboratory assay were performed at time of injection and up to 24 hours after contrast material administration. RESULTS: At MR imaging, 316 lesions were identified in 131 patients. In 77% (P.012), 72% (P =.15), and 71% (P =.027) of patients for readers 1, 2, and 3, respectively, more lesions were seen at precontrast and postcontrast MR imaging combined than at precontrast MR imaging alone. Sensitivity values for blinded readings were significantly greater at postcontrast MR imaging than at precontrast MR imaging for two of three blinded readers. For all blinded readers, combined precontrast and postcontrast MR images showed no difference in sensitivity compared with helical CT scans. The use of MR imaging, however, yielded fewer patients with at least one false-positive lesion (37%, 31 %, and 34% of patients for readers 1, 2, and 3, respectively) than did helical CT (45%, 36%, and 43% of patients for readers 1, 2, and 3, respectively). CONCLUSION: Compared with precontrast MR imaging, postcontrast MR imaging with Gd-EOB-DTPA demonstrated improved sensitivity for lesion detection in the majority of blinded readers, with no substantial adverse events. (c) RSNA, 2005. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. Berlex Labs Inc, Montville, NJ USA. Schering AG, D-1000 Berlin, Germany. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Univ Chicago Hosp, Chicago, IL 60637 USA. Presbyterian Univ Hosp, Pittsburgh, PA 15213 USA. Univ Michigan, Hlth Syst, Ann Arbor, MI 48109 USA. NYU, Med Ctr, New York, NY 10016 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Duke Univ, Med Ctr, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Univ Alabama, Birmingham, AL USA. RP Bluemke, DA (reprint author), Johns Hopkins Univ, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA. OI Bluemke, David/0000-0002-8323-8086 NR 30 TC 142 Z9 150 U1 2 U2 8 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 OCT PY 2005 VL 237 IS 1 BP 89 EP 98 DI 10.1148/radiol.2371031842 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 965RM UT WOS:000231968000015 PM 16126918 ER PT J AU Kalra, MK Rizzo, S Maher, MM Halpern, EF Toth, TL Shepard, JAO Aquino, SL AF Kalra, MK Rizzo, S Maher, MM Halpern, EF Toth, TL Shepard, JAO Aquino, SL TI Chest CT performed with z-axis modulation: Scanning protocol and radiation dose SO RADIOLOGY LA English DT Article ID TUBE CURRENT MODULATION; COMPUTED-TOMOGRAPHY; IMAGE QUALITY; ONLINE MODULATION; REDUCTION; OPTIMIZATION; EXPOSURE; CHILDREN; ABDOMEN; PELVIS AB Institutional review board approval of the study protocol and waiver of informed consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. The purpose of this study was to retrospectively assess the scanning protocol and radiation dose associated with z-axis automatic tube current modulation in multi-detector row CT scanning of the chest. Fifty-three patients (mean age, 54 years; age range, 26-77 years; 25 men, 28 women) underwent 116-detector row chest CT with z-axis modulation and noise indexes of 10.0, 12.5, and 15.0 HU. Two radiologists independently compared images acquired with z-axis modulation and fixed tube current (1180-300 mA) techniques for image noise, diagnostic acceptability, and depiction of peripheral bronchovascular markings. Tube current-time product was calculated for each study. There was good interobserver agreement between the two readers (K = 0.72). Compared with the fixed tube current technique, z-axis modulation provides acceptable image noise for chest CT, with an 18% and 26% reduction in tube current-time product at 10.0- and 12.5-HU noise indexes, respectively. (c) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. GE Med Syst, Waukesha, WI USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM mannudeep_k_kalra@yahoo.com NR 18 TC 91 Z9 114 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 OCT PY 2005 VL 237 IS 1 BP 303 EP 308 DI 10.1148/radiol.2371041227 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 965RM UT WOS:000231968000042 PM 16183938 ER PT J AU Rizzo, SMR Kalra, MK Schmidt, B Raupach, R Maher, MM Blake, MA Saini, S AF Rizzo, SMR Kalra, MK Schmidt, B Raupach, R Maher, MM Blake, MA Saini, S TI CT images of abdomen and pelvis: Effect of nonlinear three-dimensional optimized reconstruction algorithm on image quality and lesion characteristics SO RADIOLOGY LA English DT Article ID NOISE-REDUCTION FILTERS; TOMOGRAPHY AB The purpose of this study was to retrospectively assess the effect of a post-processing nonlinear three-dimensional optimized reconstruction algorithm on image quality and lesion characteristics in abdominal and pelvic computed tomographic (CT) in ages. Institutional review board a proved the HIPAA-compliant stud protocol; informed consent was waived. Abdominal and pelvic CT images (40 patients; male-female ratio, 20:20; age range, 28-86 years) at 5-mm (n = 20) and 2-mm (n = 20) section thicknesses were post-processed with the algorithm at three noise reduction levels. Image noise at the level of porta hepatis and acetabulum was evaluated with a five-point scale (1, no or minimal noise; 5, unacceptable noise), and presence and number of lesions and conspicuity were assessed. Statistical analysis was performed (Wilcoxon signed rank test, analysis of variance). Significant noise reduction was noted at all three levels with the algorithm (P <.05). Reduction in image contrast was noted with only one noise reduction level (P <.0001). The algorithm improves image noise without affecting lesion conspicuity and detection on low-dose abdominal and pelvic CT images. (c) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Siemens Med Solut, Forchheim, Germany. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM mannudeepk_kalra@yahoo.com NR 9 TC 14 Z9 14 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2005 VL 237 IS 1 BP 309 EP 315 DI 10.1148/radiol.2371041879 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 965RM UT WOS:000231968000043 PM 16183939 ER PT J AU Jones, SE Wittram, C AF Jones, SE Wittram, C TI The indeterminate CT pulmonary angiogram: Imaging characteristics and patient clinical outcome SO RADIOLOGY LA English DT Article ID VENTILATION-PERFUSION SCAN; HELICAL CT; THIN-COLLIMATION; EMBOLISM; DIAGNOSIS; AGREEMENT; RADIOLOGY AB PURPOSE: To retrospectively review imaging characteristics of indeterminate computed tomographic (CT) pulmonary angiograms for pulmonary embolism (PE) and patient outcome. MATERIALS AND METHODS: Investigational review board approval was obtained, informed consent was waived, and the study was HIPAA compliant. Retrospective review of 3612 CT pulmonary angiography reports created between July 1, 2001, and July 1, 2003, was performed with a keyword search for "indeterminate," "nondiagnostic," or "inadequate" (thereafter, all defined as "indeterminate") and yielded studies from 237 patients (mean age, 57 years; 117 men, 120 women). Randomly selected diagnostic studies were used to form a control group of 25 subjects (mean age, 64 years; eight men, 17 women). Electronic medical records were reviewed for follow-up imaging (repeat CT pulmonary angiography, conventional pulmonary angiography, ventilation-perfusion scintigraphy, or lower-extremity ultrasonography [US]), use of anticoagulation, placement of inferior vena cava (IVC) filters, clinical outcomes, and comments reqarding indeterminate reading of CT angiograms. Studies (in patients and control subjects) were reviewed for PE, contrast attenuation in the main pulmonary artery (MPA), motion artifacts, image noise, and flow artifacts. Findings were compared with two-sample t tests assuming unequal variance. RESULTS: The cause cited for indeterminism was most often motion (74%), followed by poor contrast enhancement (40%). Contrast attenuation in the MPA was 245 HU +/- 80 (standard deviation) in patients and 339 HU 88 in control subjects (P <.001). Only 46% of indeterminate studies met institutional criteria for adequate contrast attenuation in the MPA. Rereview of studies demonstrated five missed PEs. A total of 81 patients (33%) underwent follow-up imaging within 5 days, with one positive pulmonary angiograrn and four positive lower-limb US scans. Reread or follow-up images depicted thromboembolic disease in 4.2% of patients. Nineteen patients (8%) with indeterminate final result were treated for thromboembolic disease with either anticoagulation or IVC filters. Reports on 22% of indeterminate studies contained recommendations for follow-up imaging, and those recommendations nonsignificantly increased the rate for those examinations from 13% to 19%. Review of discharge summaries showed 22% of studies are clinically interpreted as negative. CONCLUSION: The two major causes of indeterminism are motion artifacts and poor contrast enhancement.(c) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Jones, SE (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM sejones@partners.org NR 15 TC 89 Z9 92 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2005 VL 237 IS 1 BP 329 EP 337 DI 10.1148/radiol.2371041520 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 965RM UT WOS:000231968000046 PM 16183940 ER PT J AU Kwek, BH Wittram, C AF Kwek, BH Wittram, C TI Postpneumonectomy pulmonary artery stump thrombosis: CT features and imaging follow-up SO RADIOLOGY LA English DT Article AB PURPOSE: To retrospectively evaluate the computed tomographic (CT) features of pulmonary artery stump thrombosis at initial and follow-up CT. MATERIALS AND METHODS: The study was approved by institutional review board, which waived informed consent, and was, HIPPA compliant. All patients who had undergone pneumonectomy and CT from January 2001 to August 2003, as identified with data search system, were included. Eighty-nine patients (49 men, 40 women; mean age, 60 years) were studied. Thrombus identification, categorization (concave or convex), and stump and thrombus measurements were made by two radiologists in consensus. The use of anticoagulation therapy was determined from patients' charts. The t test was used. RESULTS: Initial CT scans were obtained 34,months, 67 (standard, deviation) after pneumonectomy; multiple CT scans were obtained in 58 patients during. follow-up of 25.1 months +/- 24.8. Eleven (12.4%),of 89 patients had stump thrombi with near equal frequency on either side. Five concave and six convex thrombi were 1 initially identified. Anticoagulation was not commenced for stump, thrombosis. The mean length of the right stump (31 mm 10) was greater than that of the left stump (13 mm 7) (P <.01). After a right and-left pneumonectomy, there was a, significant difference between the length of the stump in, patients with (right, 40. mm +/- 14; left, 21 mm +/- 11) and patients without thrombosis (right, 30 mm left, 12 mm +/- 6) (P =.027 and P <.01, respectively). Follow-up CT scans were not available in four cases. CT findings demonstrated a reduction in thrombus size in four patients (one received anticoagulation therapy for concomitant pulmonary embolism). Two patients had stable concave thrombi, one with an initial-concave thrombus developed convex thrombus and one with an initial convex thrombus developed developed concave thrombus. No thrombi propagated outside of the stump. CONCLUSION: There is a relationship between stump length and the development of in situ thrombosis. The data suggest a rather benign natural history. (c) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, Boston, MA 02114 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. EM cwittram@partners.org NR 8 TC 11 Z9 13 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2005 VL 237 IS 1 BP 338 EP 341 DI 10.1148/radiol.2371041686 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 965RM UT WOS:000231968000047 PM 16126932 ER PT J AU Green, MF Olivier, B Crawley, JN Penn, DL Silverstein, S AF Green, MF Olivier, B Crawley, JN Penn, DL Silverstein, S TI Social cognition in schizophrenia: Recommendations from the Measurement and Treatment Research to Improve Cognition in Schizophrenia New Approaches Conference SO SCHIZOPHRENIA BULLETIN LA English DT Article; Proceedings Paper CT 7th Biennial Sinai Conference on Cognitionn in Schizophrenia CY APR 02, 2005 CL Savannah, GA DE social cognition; schizophrenia; MATRICS; animal models ID EMOTION PERCEPTION; NEURAL BASIS; MICE LACKING; BEHAVIOR; RECOGNITION; IDENTIFICATION; NEUROBIOLOGY; NEUROSCIENCE; VASOPRESSIN; PERFORMANCE AB This article summarizes the discussion from a breakout group at the National Institute of Mental Health-Measurement and Treatment Research to Improve Cognition in Schizophrenia New Approaches Conference on social cognition in schizophrenia. During this discussion, the reasons for the recent growth of research on social cognition in schizophrenia were examined. The discussion group established consensus on several points, including the importance of viewing social cognition from interdisciplinary perspectives (including outcomes research, social psychology, cognitive psychology, cognitive neuroscience, and animal models) and the need for clearer definition of terms. There was also general agreement that social cognition is a valuable construct for understanding the nature and disability of schizophrenia. One of the objectives of this group was to generate recommendations for subsequent human and animal studies, and these research agendas are summarized in this report. C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, NPI, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Utrecht, Inst Pharmacol Sci, Dept Psychopharmacol, Utrecht, Netherlands. Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. RP Green, MF (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM mgreen@ucla.edu NR 60 TC 202 Z9 212 U1 10 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD OCT PY 2005 VL 31 IS 4 BP 882 EP 887 DI 10.1093/schbul/sbi049 PG 6 WC Psychiatry SC Psychiatry GA 971ZA UT WOS:000232422400013 PM 16135561 ER PT J AU Bromley, E AF Bromley, E TI A collaborative approach to targeted treatment development for schizophrenia: A qualitative evaluation of the NIMH-MATRICS project SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; cognition; psychotropic drugs; therapeutic use; diffusion of innovation; qualitative research ID CONSENSUS COGNITIVE BATTERY; NEUROCOGNITIVE DEFICITS; IMPROVE COGNITION; CLINICAL-PRACTICE; ENDOPHENOTYPE; SUPPORT; MEMORY; CARE; PERSPECTIVE; OUTCOMES AB Introduction: In 2002, the National Institute of Mental Health (NIMH) initiated a multistakeholder research process designed to stimulate the development and evaluation of medications targeting the cognitive deficits associated with schizophrenia. The first phase, Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), sought consensus on laboratory measures for cognition, clinical trial outcome measures, and drug registration requirements. MATRICS constitutes a unique drug development model because it targeted a specific endophenotype of schizophrenia and because it engaged academic, industry, and government stakeholders in a consensus-oriented process. This study offers a preliminary qualitative evaluation of the NIMH-MATRICS project. Method: Interview data are used to describe how MATRICS participants regard 3 aspects of the development of cognitive medications: the definition of the treatment target, stakeholders' role in the early development process, and anticipated dissemination complexities. Results: MATRICS participants describe the treatment target in highly varied ways and envision a wide range of public health benefits. MATRICS is perceived as inclusive, despite minimal representation from some end users. According to informants, clinical detection, documentation, and monitoring of cognition and functioning may prove problematic. More thoroughly than non-industry-employed informants, industry-employed MATRICS participants articulate strategies by which treatments can be integrated into clinical practice. Discussion: The MATRICS process did not produce a clinical concept of cognitive impairment in schizophrenia, and significant challenges remain to be addressed regarding the rational clinical use of novel pharmaceuticals for cognition. Broader inclusion of end users in translational science projects may streamline implementation and facilitate improvements in real-world outcomes. C1 Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Bromley, E (reprint author), Mail 911 Broxton Plaza,3rd Floor, Los Angeles, CA 90024 USA. EM ebromley@ucla.edu NR 59 TC 12 Z9 12 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD OCT PY 2005 VL 31 IS 4 BP 954 EP 961 DI 10.1093/schbul/sbi059 PG 8 WC Psychiatry SC Psychiatry GA 971ZA UT WOS:000232422400021 PM 16166607 ER PT J AU Manoach, DS White, N Lindgren, KA Heckers, S Coleman, MJ Dubal, S Goff, DC Holzman, PS AF Manoach, DS White, N Lindgren, KA Heckers, S Coleman, MJ Dubal, S Goff, DC Holzman, PS TI Intact hemispheric specialization for spatial and shape working memory in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE prefrontal cortex; schizophrenia; working memory; hemispheric specialization; functional neuroimaging; laterality ID EVENT-RELATED FMRI; PREFRONTAL CORTEX; LANGUAGE LATERALIZATION; CORTICAL CONTRIBUTIONS; FRONTAL-CORTEX; FUNCTIONAL MRI; HANDEDNESS; ORGANIZATION; SCALE; LOBES AB Objective: Using functional MRI, we investigated whether, like healthy subjects, patients with schizophrenia show a relative hemispheric specialization in ventrolateral prefrontal cortex (PFC) for spatial and shape working memory (WM). We hypothesized that reduced specialization in schizophrenia would reflect a failure to adopt optimal domain-specific strategies and would contribute to WM deficits. Methods: Twelve healthy subjects and 16 schizophrenia patients performed spatial and shape WM tasks and a non-WM control task. Direct comparisons of the spatial and shape WM tasks assessed specialization. Results: Despite deficient WM performance, both patients and controls showed a relative hemispheric specialization in ventrolateral PFC for spatial (right) and shape (left) WM and did riot differ in this regard. Conclusions: The finding of intact hemispheric specialization in ventrolateral PFC suggests that patients employ the same domain-specific strategies as healthy subjects during spatial and shape WM. Rather than reflecting a failure to adopt the optimal strategy, we hypothesize that WM deficits in schizophrenia reflect impairments of executive processes that are required for WM performance regardless of domain. These processes are associated with activity in the dorsolateral PFC, a region that has been repeatedly implicated in studies of WM. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. McLean Hosp, Psychol Res Lab, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp E, 36 1st Ave,Room 420, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [K23MH01829]; PHS HHS [P01 31154, R01 31340] NR 37 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT 1 PY 2005 VL 78 IS 1 BP 1 EP 12 DI 10.1016/j.schres.2005.06.017 PG 12 WC Psychiatry SC Psychiatry GA 962QZ UT WOS:000231748600001 PM 16076549 ER PT J AU Anderson, KC Prince, HM AF Anderson, KC Prince, HM TI Lenalidomide and thalidomide: An evolving paradigm for the management of multiple myeloma - Introduction SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med,Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Neoplasia, Boston, MA 02115 USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. RP Anderson, KC (reprint author), Harvard Univ, Sch Med,Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Neoplasia, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 0 TC 11 Z9 11 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2005 VL 42 IS 4 SU 4 BP S1 EP S2 DI 10.1053/j.seminhematol.2005.10.005 PG 2 WC Hematology SC Hematology GA 995XL UT WOS:000234138100001 PM 16344096 ER PT J AU Anderson, KC AF Anderson, KC TI Lenalidomide and thalidomide: Mechanisms of action - Similarities and differences SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT 10th International Myeloma Workshop CY APR, 2005 CL Sydney, AUSTRALIA ID MULTIPLE-MYELOMA CELLS; OVERCOMES DRUG-RESISTANCE; MARROW STROMAL CELLS; MOLECULAR-MECHANISMS; MM CELLS; ANALOGS; GROWTH; APOPTOSIS; ANGIOGENESIS; BORTEZOMIB C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Hematol Neoplasia, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Hematol Neoplasia, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 18 TC 133 Z9 140 U1 1 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2005 VL 42 IS 4 SU 4 BP S3 EP S8 DI 10.1053/j.seminhematol.2005.10.001 PG 6 WC Hematology SC Hematology GA 995XL UT WOS:000234138100002 PM 16344099 ER PT J AU Richardson, P AF Richardson, P TI Management of the relapsed/refractory myeloma patient: Strategies incorporating lenalidomide SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT 10th International Myeloma Workshop CY APR, 2005 CL Sydney, AUSTRALIA ID REFRACTORY MULTIPLE-MYELOMA; POTENT INHIBITORS; DRUG-RESISTANCE; TNF-ALPHA; THALIDOMIDE; ANALOGS; CC-5013; MM; THERAPY; CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Hematol Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Hematol Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St,D1B30, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 16 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2005 VL 42 IS 4 SU 4 BP S9 EP S15 DI 10.1053/j.seminhematol.2005.10.004 PG 7 WC Hematology SC Hematology GA 995XL UT WOS:000234138100003 PM 16344100 ER PT J AU Krieger, N Smith, K Naishadham, D Hartman, C Barbeau, EM AF Krieger, N Smith, K Naishadham, D Hartman, C Barbeau, EM TI Experiences of discrimination: Validity and reliability of a self-report measure for population health research on racism and health SO SOCIAL SCIENCE & MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Building Trust and Value in Health systems in Low- and Middle-Income Countries CY OCT, 2002 CL Johannesburg, SOUTH AFRICA SP Ctr Hlth Policy, Univ Witwatersrand, Hlth Econ & Financing Programme, London Sch Hygiene & Tropical Med, Social & Public Hlth Econ Res Grp, Curtin Univ DE racial discrimination; validity; reliability; psychometric; black; Latino; USA ID AFRICAN-AMERICAN; PERCEIVED DISCRIMINATION; BLOOD-PRESSURE; MENTAL-HEALTH; UNITED-STATES; ADULTS; RISK AB Population health research on racial discrimination is hampered by a paucity of psychometrically validated instruments that can be feasibly used in large-scale studies. We therefore sought to investigate the validity and reliability of a short self-report instrument, the "Experiences of Discrimination" (EOD) measure, based on a prior instrument used in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Study participants were drawn from a cohort of working class adults, age 25-64, based in the Greater Boston area, Massachusetts (USA). The main study analytic sample included 159 black, 249 Latino, and 208 white participants; the validation study included 98 African American and 110 Latino participants who completed a re-test survey two to four weeks after the initial survey. The main and validation survey instruments included the EOD and several single-item discrimination questions; the validation survey also included the Williams Major and Everyday discrimination measures. Key findings indicated the EOD can be validly and reliably employed. Scale reliability was high, as demonstrated by confirmatory factor analysis, Cronbach's alpha (0.74 or greater), and test-re-test reliability coefficients (0.70). Structural equation modeling demonstrated the EOD had the highest correlation (r = 0.79) with an underlying discrimination construct compared to other self-report discrimination measures employed. It was significantly associated with psychological distress and tended to be associated with cigarette smoking among blacks and Latinos, and it was not associated with social desirability in either group. By contrast, single-item measures were notably less reliable and had low correlations with the multi-item measures. These results underscore the need for using validated, multi-item measures of experiences of racial discrimination and suggest the EOD may be one such measure that can be validly employed with working class African Americans and Latino Americans. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02472 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Krieger, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM nkrieger@hsph.harvard.edu; kevinsmith@rti.org; dnaishadham@neri.org; cathy_hartman@dfci.harvard.edu; elizabeth_barbeau@dfci.harvard.edu FU NIOSH CDC HHS [1R01 OHO7366-01] NR 48 TC 399 Z9 401 U1 7 U2 62 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 OCT PY 2005 VL 61 IS 7 BP 1576 EP 1596 DI 10.1016/j.socscimed.2005.03.006 PG 21 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 952RY UT WOS:000231024400020 PM 16005789 ER PT J AU Goffaux, J Friesinger, GC Lambert, W Shroyer, LW Moritz, TE McCarthy, M Henderson, WG Hammermeister, KE AF Goffaux, J Friesinger, GC Lambert, W Shroyer, LW Moritz, TE McCarthy, M Henderson, WG Hammermeister, KE TI Biological age - A concept whose time has come: A preliminary study SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID MINI-MENTAL-STATE; ACUTE MYOCARDIAL-INFARCTION; BYPASS GRAFT-SURGERY; FUNCTIONAL STATUS; OLDER-ADULTS; CONTINUOUS IMPROVEMENT; CARDIOVASCULAR HEALTH; PHYSICAL PERFORMANCE; CALCULATING RISK; ELDERLY-PATIENTS AB Objective: Chronology poorly predicts biological age (BA) or physiologic reserve (PR). An objective approach to the heterogeneity of aging would greatly help clinical decision making in the elderly. Materials And Methods: The first pilot study evaluated 130 "healthy" volunteers, ages 70 to 95 years. A summary BA/PR index was developed, using measures of endurance, strength, flexibility, balance, cognition, depression, comorbidity, and exercise. The second study applied the BA/PR concept to prediction of death after a first elective coronary artery bypass graft, using a Veterans Administration database. Results: The BA/PR index was a better predictor of 3-year functional outcomes and death than was chronological age. In the coronary artery bypass graft Study, the inclusion of BA/PR variables significantly improved prediction of 6-month and long-term death for Veterans Administration patients. Conclusions: The usefulness of a biological age (BA/PR) approach in predicting outcomes in the elderly was supported. Needed research Should develop tools for routine "tracking" of the aging process. C1 Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN 37232 USA. Vanderbilt Univ, Inst Publ Policy Studies, Nashville, TN 37232 USA. Denver VA Med Ctr, Cardiol Sect 111B, Denver, CO USA. Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program, Coordinating Ctr, Chicago, IL USA. Northwestern Univ, Colorado Hlth Outcomes Program F 443, Chicago, IL 60611 USA. RP Friesinger, GC (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, 383 PRB,2220 Pierce Ave, Nashville, TN 37232 USA. EM Gottlieb.friesinger@vanderbilt.edu RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 89 TC 7 Z9 7 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD OCT PY 2005 VL 98 IS 10 BP 985 EP 993 DI 10.1097/01.smj.0000182178.22607.47 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 982RC UT WOS:000233178300008 PM 16295813 ER PT J AU Frisbie, JH Sharma, GVRK Brahma, P Hess, MJ Hayes, JA AF Frisbie, JH Sharma, GVRK Brahma, P Hess, MJ Hayes, JA TI Recurrent pulmonary embolism and pulmonary hypertension in chronic tetraplegia SO SPINAL CORD LA English DT Article DE pulmonary embolism; pulmonary hypertension; spinal cord injury; tetraplegia; quadriplegia; prostatic cancer ID SPINAL-CORD-INJURY; VENOUS THROMBOEMBOLISM; HYPOTENSION; MYELOPATHY; THROMBOSIS; CANCER AB Study design: Case report. Objective: To describe an unusual case of progressive pulmonary hypertension due to recurrent pulmonary embolism in a chronically paralyzed spinal cord injury patient. Setting: Veterans Administration Hospital, West Roxbury, MA, USA. Subject: A 57-year-old man, tetraplegic, sensory incomplete and motor complete for 30 years due to a diving accident, complained of lightheadedness and shortness of breath intermittently for 7 years. Examination during the latest episode revealed anxiety, confusion, respirations 28 per min, blood pressure 80/60 mmHg, and arterial pH 7.41, P-CO2 28 mmHg, P-O2 95 mmHg on 2 l of oxygen. A chest film 2 weeks earlier had revealed a right-sided cutoff of pulmonary vasculature; the current film showed right-sided pleural effusion. Review of EKGs showed a trend of increasing right axis deviation with recovery and recurrences during the previous 9 years and a current incomplete right bundle branch block with clockwise rotation and inverted T waves in V1 - 4. Computerized tomography with contrast material revealed small pulmonary emboli, but only in retrospect. The patient died shortly after scanning. Autopsy: The pulmonary arteries were free of thromboemboli on gross examination but medium and small-sized arteries were constricted or obliterated with thrombotic material microscopically. The estimated ages of the thromboemboli ranged from days to years. The right ventricle was hypertrophied; the coronary arteries were patent. Conclusion: Recurrent pulmonary emboli resulted in chronic pulmonary hypertension and eventual death in a patient with chronic tetraplegia. C1 Dept Vet Affairs Med Ctr, Spinal Cord Injury Serv, W Roxbury, MA 02492 USA. Dept Med Affairs Med Ctr, Med Serv, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Dept Med Affairs Med Ctr, Pathol Serv, W Roxbury, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Frisbie, JH (reprint author), Dept Vet Affairs Med Ctr, Spinal Cord Injury Serv 128, 1400 Vet Foreign Wars Pkwy, W Roxbury, MA 02492 USA. NR 32 TC 4 Z9 5 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD OCT PY 2005 VL 43 IS 10 BP 625 EP 630 DI 10.1038/sj.sc.3101745 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 971LQ UT WOS:000232386000009 PM 15852059 ER PT J AU Bellamy, SL Li, Y Lin, XH Ryan, LM AF Bellamy, SL Li, Y Lin, XH Ryan, LM TI Quantifying PQL bias in estimating cluster-level covariate effects in generalized linear mixed models for group-randomized trials SO STATISTICA SINICA LA English DT Article DE asymptotic bias; asymptotic variance; generalized linear mixed models; penalized quasilikelihood ID REGRESSION-MODELS; INFERENCE; DISPERSION AB We derive the asymptotic bias and variance of the penalized quasilikelihood (PQL) estimator of the cluster-level covariate effect in generalized linear mixed models for group-randomized trials where the number of clusters n is small and the cluster size m is large. We show that the asymptotic bias is of order O-p(1/m) and the asymptotic variance is of order Op(1/n) + Op{1/(nm)}. The practical implication of our results is that the PQL method works well in settings involving small numbers of large clusters which are typical in grouped randomized trials. We illustrate the results using simulation studies. C1 Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bellamy, SL (reprint author), Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. EM sbellamy@cceb.upenn.edu; yili@hsph.harvard.edu; xlin@hsph.harvard.edu; lryan@hsph.harvaxd.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 16 TC 6 Z9 6 U1 0 U2 2 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD OCT PY 2005 VL 15 IS 4 BP 1015 EP 1032 PG 18 WC Statistics & Probability SC Mathematics GA 012AY UT WOS:000235311800010 ER PT J AU Rodic, N Oka, M Hamazaki, T Murawski, MR Jorgensen, M Maatouk, DM Resnick, JL Li, E Terada, N AF Rodic, N Oka, M Hamazaki, T Murawski, MR Jorgensen, M Maatouk, DM Resnick, JL Li, E Terada, N TI DNA methylation is required for silencing of Ant4, an adenine nucleotide translocase selectively expressed in mouse embryonic stem cells and germ cells SO STEM CELLS LA English DT Article DE embryonic stem cell; DNA methylation; differentiation; germ cell; adenine nucleotide translocase; gene repression ID ADP ATP TRANSLOCASE; GENE-EXPRESSION; SOMATIC-CELLS; CYTOCHROME-C; IN-VITRO; ES CELLS; METHYLTRANSFERASES; DIFFERENTIATION; IDENTIFICATION; CHROMATIN AB The capacity for cellular differentiation is governed not only by the repertoire of available transcription factors but by the accessibility of cis-regulatory elements. Studying changes in epigenetic modifications during stem cell differentiation will help us understand how cells maintain or lose differentiation potential. We investigated changes in DNA methylation during the transition of pluripotent embryonic stem cells (ESCs) into differentiated cell types. Using a methylation-sensitive restriction fingerprinting method, we identified a novel adenine nucleotide (ADP/ATP) translocase gene, Ant4, that was selectively hypomethylated and expressed in undifferentiated mouse ESCs. In contrast to other pluripotent stem cell-specific genes such as Oct-4 and Nanog, the Ant4 gene was readily derepressed in differentiated cells after 5-aza-2'-deoxycytidine treatment. Moreover, expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b was essential for repression and DNA methylation of the Ant4 gene during ESC differentiation. Although the deduced amino acid sequence of Ant4 is highly homologous to the previously identified Ant isoforms, the expression of Ant4 was uniquely restricted to developing gametes in adult mice, and its promoter hypomethylation was observed only in testis. Additionally, Ant4 was expressed in primordial germ cells. These data indicate that Ant4 is a pluripotent stem cell- and germ cell-specific isoform of adenine nucleotide translocase in mouse and that DNA methylation plays a primary role in its transcriptional silencing in somatic cells. C1 Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Shands Canc Ctr, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Terada, N (reprint author), Univ Florida, Coll Med, Dept Pathol, 1600 SW Archer Rd, Gainesville, FL 32610 USA. EM terada@pathology.ufl.edu FU NCRR NIH HHS [RR17001]; NIDDK NIH HHS [DK59699] NR 41 TC 60 Z9 64 U1 0 U2 4 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD OCT PY 2005 VL 23 IS 9 BP 1314 EP 1323 DI 10.1634/stemcells.2005-0119 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 975OV UT WOS:000232672700011 PM 16051982 ER PT J AU Rikitake, Y Kim, HH Huang, ZH Seto, M Yano, K Asano, T Moskowitz, MA Liao, JK AF Rikitake, Y Kim, HH Huang, ZH Seto, M Yano, K Asano, T Moskowitz, MA Liao, JK TI Inhibition of rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection SO STROKE LA English DT Article DE cerebral blood flow; nitric oxide; stroke ID NITRIC-OXIDE SYNTHASE; REDUCTASE INHIBITORS; DOWN-REGULATION; L-ARGININE; ISCHEMIA; MICE; PATHOGENESIS; INVOLVEMENT; INFARCTION; VASOSPASM AB Background and Purpose - Endothelium-derived nitric oxide (NO) plays a pivotal role in vascular protection. The Rho kinase (ROCK) inhibitor, hydroxyfasudil, prevents the downregulation of endothelial NO synthase (eNOS) under hypoxic conditions. However, it is unknown whether inhibition of ROCK can attenuate ischemia- induced endothelial dysfunction and tissue damage in vivo. Methods - Human vascular endothelial cells were treated with increasing concentrations of hydroxyfasudil (0.1 to 100 mu mol/ L) and eNOS expression and activity were measured. To determine the physiological relevance of eNOS regulation by ROCK, we administered fasudil, which is metabolized to hydroxyfasudil in vivo, to mice for 2 days before subjecting them to middle cerebral artery occlusion. Cerebral blood flow, cerebral infarct size, and neurologic deficit were measured. Results - In a concentration-dependent manner, hydroxyfasudil increased eNOS mRNA and protein expression, resulting in a 1.9- and 1.6- fold increase, respectively, at 10 mu mol/ L (P < 0.05 for both). This correlated with a 1.5- and 2.3- fold increase in eNOS activity and NO production, respectively (P < 0.05 for both). Fasudil increased cerebral blood flow to both ischemic and nonischemic brain areas, reduced cerebral infarct size by 33%, and improved neurologic deficit score by 37% (P < 0.05). This correlated with inhibition of brain and vascular ROCK activity and increased eNOS expression and activity. Another ROCK inhibitor, Y-27632, also showed similar effects. The neuroprotective effects of fasudil were absent in eNOS-deficient mice. Conclusions - These findings indicate that the neuroprotective effect of ROCK inhibition is mediated by endothelium-derived NO and suggest that ROCK may be an important therapeutic target for ischemic stroke. C1 Brigham & Womens Hosp, Vasc Med Res Unit, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lab Stroke & Neurovasc Regulat, Boston, MA 02114 USA. Asahi Kasei Pharma Corp, Life Sci Res Inst, Fuji, Shizuoka, Japan. RP Liao, JK (reprint author), Brigham & Womens Hosp, Vasc Med Res Unit, Div Cardiovasc, 65 Landsdowne St,Rm 275, Cambridge, MA 02139 USA. EM jliao@rics.bwh.harvard.edu RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [HL52233, R01 HL052233, R01 HL052233-05, R01 HL052233-06, R01 HL052233-07, R01 HL070274, R01 HL070274-01, R01 HL070274-02, R01 HL070274-03]; NIDDK NIH HHS [R01 DK062729-01A1, R01 DK062729, R01 DK062729-02]; NINDS NIH HHS [F32 NS010828, NS10828, P01 NS010828, P01 NS010828-330036, P50 NS010828, P50 NS010828-290036] NR 26 TC 205 Z9 241 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2005 VL 36 IS 10 BP 2251 EP 2257 DI 10.1161/01.STR.0000181077.84981.11 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 968OV UT WOS:000232172700051 PM 16141422 ER PT J AU Mitchell, AM Kim, Y Prigerson, HG Mortimer, MK AF Mitchell, AM Kim, Y Prigerson, HG Mortimer, MK TI Complicated grief and suicidal ideation in adult survivors of suicide SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID TRAUMATIC GRIEF; MEASURING DEPRESSION; INVENTORY; RISK; VALIDATION; DISORDERS; CRITERIA AB While the prevalence of complicated grief has been demonstrated to be elevated in survivors of suicide, the association between complicated grief and suicidal ideation among adult suvivors of suicide has not been explored. The purpose of the present study is to examine the association between complicated grief and suicidal ideation in suicide survivors. The Inventory of Complicated Grief and the Beck Depression Inventory were administered to 60 adult survivors within 1 month of a death by suicide of a family member or significant other. Complicated grief was associated with a 9.68 (CI: 1.036, 90.417) times greater likelihood of suicidal ideation after controlling for depression, suggesting that syndromal complicated grief heightens vulnerability to suicidal ideation. Clinicians may provide more comprehensive assessments by recognizing the possibility of suicidal ideation in those with complicated grief. C1 Univ Pittsburgh, Sch Nursing, Hlth & Community Syst Dept, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Nursing, Ctr Nursing Res, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Franciscan Univ, Steubenville, OH USA. RP Mitchell, AM (reprint author), Univ Pittsburgh, Sch Nursing, Hlth & Community Syst Dept, 415 Victoria Bldg, Pittsburgh, PA 15261 USA. EM ammi@pitt.edu NR 27 TC 43 Z9 43 U1 2 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD OCT PY 2005 VL 35 IS 5 BP 498 EP 506 DI 10.1521/suli.2005.35.5.498 PG 9 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 981ES UT WOS:000233070800002 PM 16268767 ER PT J AU Brenner, BE Holmes, TM Mazal, B Camargo, CA AF Brenner, BE Holmes, TM Mazal, B Camargo, CA TI Relation between phase of the menstrual cycle and asthma presentations in the emergency department SO THORAX LA English DT Article ID AIRWAY RESPONSIVENESS; PREMENSTRUAL ASTHMA; BRONCHIAL-ASTHMA; SEX-DIFFERENCES; PREGNANCY; ESTROGEN; ADULTS; WOMEN; FLOW; AGE AB Background: The phase of the menstrual cycle is thought to influence the course of asthma in women. One recent study reported a large increase in exacerbations during the perimenstrual phase, while another found a preovulatory increase. A study was undertaken to determine the relation between phase of the menstrual cycle and acute asthma in patients presenting to the emergency department (ED). Methods: All women aged 18-54 years presenting with a diagnosis of acute asthma exacerbation were considered for enrolment in the study. Women who were pregnant, postmenopausal, following hysterectomy, with a >28 day menstrual cycle or incomplete reproductive history were excluded. The 792 eligible women were classified by menstrual phase based on both date of symptom onset and date of ED visit. Results: When classified by date of symptom onset, 28% were preovulatory (days 5 to 11), 25% were periovulatory (days 12 to 18), 21% were postovulatory (days 19 to 25), and 27% were perimenstrual (days 26 to 4; p = 0.03). When classified by date of ED visit, 28% were preovulatory, 22% were periovulatory, 22% were postovulatory, and 27% were perimenstrual (p = 0.004). Using either approach, there were no significant differences in demographic factors or in asthma severity of women in the various menstrual phase groups. Conclusion: Acute asthma exacerbations do not markedly increase during the perimenstrual phase. The results support the suggestion that both preovulatory and perimenstrual phases are actual triggers of asthma exacerbation in some women, or that these two phases serve as "co-factors'' that worsen other recognised triggers of acute asthma. C1 Univ Arkansas Med Sci, Univ Hosp, Dept Emergency Med, Little Rock, AR 72205 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. RP Brenner, BE (reprint author), Univ Arkansas Med Sci, Dept Emergency Med, Little Rock, AR 72205 USA. EM brennerbarry@uams.edu FU NIAID NIH HHS [AI-52338] NR 33 TC 25 Z9 25 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD OCT PY 2005 VL 60 IS 10 BP 806 EP 809 DI 10.1136/thx.2004.033928 PG 4 WC Respiratory System SC Respiratory System GA 968QS UT WOS:000232177800007 PM 16192365 ER PT J AU Siegel, M Albers, AB Cheng, DM Biener, L Rigotti, NA AF Siegel, M Albers, AB Cheng, DM Biener, L Rigotti, NA TI Effect of local restaurant smoking regulations on progression to established smoking among youths SO TOBACCO CONTROL LA English DT Article ID UNITED-STATES; ADOLESCENT SMOKING; REGRESSION-MODELS; MASSACHUSETTS; PROTECTION; TOWN AB Background: While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis. Objective: To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents. Design, setting, and subjects: A cohort of 2623 Massachusetts youths, ages 12-17 years at baseline, was interviewed via random digit dial telephone survey in 2001-2002 and followed up two years later. A generalised estimating equations (GEE) logistic regression analysis was used and controlled for potential individual, household, and town level confounding factors. Main outcome measure: Progression to established smoking during the two year follow up period (defined as having smoked 100 or more cigarettes in one's life). Results: Compared to youths living in towns with weak regulations, those living in towns with strong regulations (complete restaurant smoking bans) had less than half the odds of progression to established smoking (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.24 to 0.66). The association was stronger for youths in towns with strong regulations in effect for two or more years (OR 0.11, 95% CI 0.03 to 0.37), although it was still present for those in towns with strong regulations in effect for less than two years (OR 0.55, 95% CI 0.33 to 0.90). No relationship was found between living in a town with a medium restaurant smoking regulation (restriction of smoking to enclosed, separately ventilated areas) and rates of progression to established smoking. Conclusions: Local restaurant smoking bans may be an effective intervention to prevent youth smoking. C1 Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Siegel, M (reprint author), Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, 715 Albany St,TW2, Boston, MA 02118 USA. EM mbsiegel@bu.edu OI Biener, Lois/0000-0002-4130-8138 FU NCI NIH HHS [5 R01 CA86257-04, R01 CA086257] NR 37 TC 50 Z9 50 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD OCT PY 2005 VL 14 IS 5 BP 300 EP 306 DI 10.1136/tc.2005.012302 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 967CP UT WOS:000232069400012 PM 16183980 ER PT J AU Barbeau, EM Kelder, G Ahmed, S Mantuefel, V Balbach, ED AF Barbeau, EM Kelder, G Ahmed, S Mantuefel, V Balbach, ED TI From strange bedfellows to natural allies: the shifting allegiance of fire service organisations in the push for federal fire-safe cigarette legislation SO TOBACCO CONTROL LA English DT Article ID TOBACCO INDUSTRY DOCUMENTS; AIR-QUALITY; DEPOSITORY; SMOKE; LABOR AB Background: Cigarettes are the leading cause of fatal fires in the USA and are associated with one in four fire deaths. Although the technology needed to make fire-safe cigarettes has been available for many years, progress has been slow on legislative and regulatory fronts to require the tobacco industry to manufacture fire-safe cigarettes. Method and results: We conducted a case study, drawing on data from tobacco industry documents, archives, and key informant interviews to investigate tobacco industry strategies for thwarting fire-safe cigarette legislation in the US Congress. We apply a theoretical framework that posits that policymaking is the product of three sets of forces: interests, institutions, and ideas, to examine tobacco industry behaviour, with a special focus on their and others' attempts to court fire service organisations, including firefighters' unions as allies. We discuss the implications of our findings for future policy efforts related to fire-safe cigarettes and other tobacco control issues. Conclusions: Tobacco control advocates ought to: continue efforts to align key interest groups, including the firefighters unions; contest tobacco industry "diversionary'' science tactics; and pursue a state based legislative strategy for fire-safe cigarettes, building towards national legislation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, Medford, MA 02155 USA. RP Barbeau, EM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM elizabeth_barbeau@dfci.harvard.edu FU NCI NIH HHS [5R01CA95964-03] NR 62 TC 7 Z9 7 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD OCT PY 2005 VL 14 IS 5 BP 338 EP 345 DI 10.1136/tc.2004.010637 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 967CP UT WOS:000232069400017 PM 16183985 ER PT J AU Rodriguez-Barbosa, JI Haller, GW Zhao, GL Sachs, DH Sykes, M AF Rodriguez-Barbosa, JI Haller, GW Zhao, GL Sachs, DH Sykes, M TI Host thymectomy and cyclosporine lead to unstable skin graft tolerance after class I mismatched allogeneic neonatal thymic transplantation in mice SO TRANSPLANT IMMUNOLOGY LA English DT Article DE tolerance; allogeneic thymus transplantation; class I MHC mismatched ID MAJOR HISTOCOMPATIBILITY BARRIER; MINIATURE SWINE; POSITIVE SELECTION; RENAL-ALLOGRAFTS; T-CELLS; PERIPHERAL TOLERANCE; NEGATIVE SELECTION; AUTOIMMUNE-DISEASE; STABLE INDUCTION; DENDRITIC CELLS AB Background: Our laboratory has demonstrated that xenogeneic porcine thymus tissue grafted in thymectomized (ATX) and T cell-depleted mice induces donor-specific tolerance. Recipient thymectomy is essential for the success of tolerance induction. In contrast, studies in pigs grafted with non-vascularized allogeneic class I mismatched thymus tissue under the cover of CyA have shown that removal of host thymus is detrimental to thymic graft survival. To determine the requirements for nonvascularized allogeneic class I-mismatched thymic engraftment in mice, we performed thymic allotransplantation under the cover of CyA. Materials and methods: Euthymic and ATX B10.MBR mice received class I mismatched B10.AKM neonatal mouse thymus (NMTHY) tissue under the kidney Capsule with or without a short course of CyA. The grafts were allowed to engraft for two and a half months before exploratory laparotomy was performed to evaluate them. Three months after the thymic transplant, mice were challenged with donor-specific skin grafts to assess tolerance. One month after donor-specific skin grafting, they received third party B10.BR skin grafts. Cellular anti-donor immune responses were studied at the time of euthanasia. Results: CyA-treated ATX and euthymic control mice showed good engraftment of the allogeneic thymic tissue at the time of exploratory laparotomy, whereas non-CyA-treated ATX and euthymic controls had rejected the grafts. The CyA-treated ATX B10.MBR mice accepted donor-specific skin grafts, but rejected them following a challenge with third party B10.BR skin grafts. Untreated ATX and euthymic mice and 6 of 7 CyA-treated euthymic mice rejected donor skin within 15 days. Mixed lymphocyte reactions did not show an increased anti-donor response, but CML clearly showed sensitization and increased killing activity against donor-type targets in these mice. Conclusion: Allogeneic thymic transplantation across a class I MHC barrier under the cover of CyA induces a metastable state of tolerance in mice. To achieve this state, ATX of the recipient is required. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011; OI Rodriguez-Barbosa, Jose-Ignacio/0000-0001-7427-5654 FU NIAID NIH HHS [P01AI39755] NR 46 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD OCT PY 2005 VL 15 IS 1 BP 25 EP 33 DI 10.1016/j.trim.2005.04.004 PG 9 WC Immunology; Transplantation SC Immunology; Transplantation GA 982SG UT WOS:000233181300004 PM 16223670 ER PT J AU Papas, KK Avgoustiniatos, ES Tempelman, LA Weir, GC Colton, CK Pisania, A Rappel, MJ Friberg, AS Bauer, AC Hering, BJ AF Papas, KK Avgoustiniatos, ES Tempelman, LA Weir, GC Colton, CK Pisania, A Rappel, MJ Friberg, AS Bauer, AC Hering, BJ TI High-density culture of human islets on top of silicone rubber membranes SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 10th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA) CY MAY 04-07, 2005 CL Geneva, SWITZERLAND ID TRANSPLANTATION; LANGERHANS AB Islet culture has emerged as a standard practice prior to clinical transplantation. However, culturing large numbers of islets requires low islet density (number of islets per unit surface area) and, consequently, 20 to 30 flasks per pancreas in order to avoid hypoxia-induced death (HID). There is a need for a simple, practical, small-footprint culture vessel that will accommodate aseptic maintenance of entire human islet isolations while avoiding HID. In this communication, we examine the hypothesis that by improving oxygen transfer through culture of islets on silicone rubber membranes (SRM), we may increase islet surface coverage and reduce the number of flasks required while avoiding HID. Our results demonstrate that islets cultured for up to 48 hours in vessels with SRM bottoms at 2000 to 4000 islet equivalents (IE)/cm(2), a surface coverage 10- to 20-fold higher than the standard culture protocol, displayed no significant loss of viability. In contrast, islets cultured for 48 hours at 4000 IE/cm(2) in flasks with gas-impermeable bottoms suffered a 60% to 70% reduction in viability. The data suggest that it is possible to culture all islets isolated from a human pancreas on SRM in a single, standard-sized vessel while maintaining the same viability as with the current, standard culture protocols that require 20 to 30 flasks. This approach may lead to substantial improvements in islet culture for research and clinical transplantation. C1 Univ Minnesota, Sch Med, Diabet Inst Immunol & Transplantat, Dept Surg, Minneapolis, MN 55455 USA. Giner Inc, Newton, MA USA. Harvard Univ, Sch Med, Islet Transplantat, Joslin Diabet Ctr, Boston, MA USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Papas, KK (reprint author), Univ Minnesota, Sch Med, Diabet Inst Immunol & Transplantat, Dept Surg, Mayo Mail Code 280,420 Delaware St SE, Minneapolis, MN 55455 USA. EM papas006@umn.edu RI Bauer, Andrea/F-5891-2015; Bauer, Andrea/I-7813-2015 OI Bauer, Andrea/0000-0002-5041-4792 FU NCRR NIH HHS [U42 RR 016598-01]; NIDDK NIH HHS [N44 DK 32535] NR 12 TC 28 Z9 29 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD OCT PY 2005 VL 37 IS 8 BP 3412 EP 3414 DI 10.1016/j.transproceed.2005.09.086 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 986KV UT WOS:000233449400053 PM 16298611 ER PT J AU Bloch, KD Janssens, S AF Bloch, KD Janssens, S TI Cardiomyocyte-specific overexpression of nitric oxide synthase 3: Impact on left ventricular function and myocardial infarction SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID MYOCYTE-SPECIFIC OVEREXPRESSION; ISCHEMIA-REPERFUSION INJURY; HEART-FAILURE; CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; KNOCKOUT MICE; INHIBITION; GENE; RAT; NO AB Identification of all three nitric oxide (NO) synthase (NOS) isoforms in cardiac myocytes and the recognition of the importance of their subcellular localization have greatly advanced the understanding of the critical role of NO signaling in myocardial function. Targeted deletion of endothelial NOS (NOS3) has revealed a fundamental role for this NOS isoform in the structural and functional responses of the heart to pressure and volume overload. The recent generation of transgenic models with overexpression of NOS3 restricted to the cardiac myocyte has enabled a unique appreciation of the ability of NO to modulate cardiac muscle, independent of changes in cardiac loading conditions. Consistent with the targeting of overexpressed NOS3 to caveolae in the vicinity of cholinergic and adrenergic receptors, these studies have highlighted the importance of NOS3-derived NO in the modulation of autonomic cardiac stimulation. In vivo models of myocardial infarction suggest that NOS3 overexpression can limit compensatory hypertrophy in the remote myocardium and preserve left ventricular performance. Development of therapeutic strategies designed to enhance NO signaling in cardiac myocytes may target maladaptive left ventricular remodeling and improve functional recovery after myocardial infarction. (c) 2005, Elsevier Inc. C1 Harvard Univ, Cardiovasc Res Ctr, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Katholieke Univ Leuven, Ctr Transgene Technol & Gene Therapy, Fanders Interuniv Inst Biotechnol, Louvain, Belgium. Katholieke Univ Leuven, Cardiac Unit, Louvain, Belgium. RP Bloch, KD (reprint author), Harvard Univ, Cardiovasc Res Ctr, Sch Med, Massachusetts Gen Hosp, CBY4,149 13th St, Charlestown, MA 02129 USA. EM kdbloch@partners.org FU NHLBI NIH HHS [HL 070896] NR 31 TC 9 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD OCT PY 2005 VL 15 IS 7 BP 249 EP 253 AR PII S1050-1738(05)00125-8 DI 10.1016/j.tcm.2005.07.005 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 981PH UT WOS:000233100000003 PM 16226679 ER PT J AU Letai, A AF Letai, A TI BCL-2: found bound and drugged! SO TRENDS IN MOLECULAR MEDICINE LA English DT Article AB The BCL-2 gene was first cloned in 1985 from the t(14;18) chromosomal translocation found in nearly all follicular lymphomas. BCL-2 is understood to have a central role in inhibiting apoptosis. Now, Oltersdorf et al. report the development of a high-affinity, mechanistically validated small-molecule antagonist of BCL-2 that kills cancer in mouse xenograft models and primary human cancer cells in vitro. The two decades spanning these two achievements provide an interesting case study of rational drug development. The investigation of antiapoptotic protein antagonists holds new promise for selectively inducing programmed cell death in cancer cells. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 530 B,44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu FU NCI NIH HHS [CA 10254] NR 18 TC 32 Z9 32 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD OCT PY 2005 VL 11 IS 10 BP 442 EP 444 DI 10.1016/j.molmed.2005.08.007 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 980ZU UT WOS:000233057500002 PM 16150641 ER PT J AU Kawase, Y Hoshino, K Yoneyama, R McGregor, J Hajjar, RJ Jang, IK Hayase, M AF Kawase, Y Hoshino, K Yoneyama, R McGregor, J Hajjar, RJ Jang, IK Hayase, M TI In vivo volumetric analysis of coronary stent using optical coherence tomography with a novel balloon occlusion-flushing catheter: A comparison with intravascular ultrasound SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE new modality; imaging; catheterization; IVUS; OCT; stent ID ATHEROSCLEROTIC PLAQUES; VISUALIZATION; ARTERIES AB Optical coherence tomography (OCT) is limited as an intravascular imaging tool because of interference with blood. This study tested a new balloon occlusion-flushing catheter for OCT scanning of stented coronary arteries and compared stent measurements between OCT and intravascular ultrasound (IVUS). Motorized pullback with OCT and IVUS was examined in coronary stents deployed in swine. Quantitative measurements were obtained and compared between both groups. In addition, stent strut thickness was compared among OCT, IVUS and actual measurement. The occlusion catheter successfully provided motorized pullback OCT images in the stented coronary arteries without any complications. There were no differences in calculated lumen volume. However, stent volumes were significantly smaller with OCT than with IVUS (p < 0.05). OCT significantly underestimated the stent strut thickness compared with the actual measurement. Although OCT underestimates the stent strut thickness, motorized pullback OCT imaging with the occlusion catheter can provide appropriate in-stent images in the porcine coronary arteries. C1 Harvard Univ, Cardiol Lab Integrat Physiol & Imaging, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kawase, Y (reprint author), Harvard Univ, Cardiol Lab Integrat Physiol & Imaging, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 161, Boston, MA 02114 USA. EM ykawase@partners.org NR 18 TC 34 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD OCT PY 2005 VL 31 IS 10 BP 1343 EP 1349 DI 10.1016/j.ultrasmedbio.2005.05.010 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 974VC UT WOS:000232618500007 PM 16223637 ER PT J AU Ko, CY Maggard, M Agustin, M AF Ko, CY Maggard, M Agustin, M TI Quality in surgery: Current issues for the future SO WORLD JOURNAL OF SURGERY LA English DT Article ID 10-YEAR PROSPECTIVE COHORT; COLON-CANCER RESECTION; 8 COMMON OPERATIONS; HOSPITAL VOLUME; IMPROVEMENT PROGRAM; TECHNOLOGY-ASSESSMENT; HEALTH-CARE; RADICAL PROSTATECTOMY; PATIENT OUTCOMES; SURGICAL VOLUME C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Surg Outcomes & Qual, Dept Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Surg Outcomes & Qual, Dept Surg, 10833 Ave CHS Room 72-215, Los Angeles, CA 90095 USA. EM cko@mednet.ucla.edu NR 55 TC 19 Z9 19 U1 1 U2 1 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 OCT PY 2005 VL 29 IS 10 BP 1204 EP 1209 DI 10.1007/s00268-005-7990-y PG 6 WC Surgery SC Surgery GA 973AH UT WOS:000232494800002 PM 16136282 ER PT J AU Khuri, SF Henderson, WG AF Khuri, SF Henderson, WG TI The case against volume as a measure of quality of surgical care SO WORLD JOURNAL OF SURGERY LA English DT Article ID IMPROVEMENT PROGRAM; RISK-FACTORS; MORTALITY; OPERATIONS; STANDARDS AB Healthcare purchasers, represented by the Leapfrog Group, have attempted to set standards for "quality" of surgical care that include a minimum volume for each of five major surgical procedures, with the assumption that higher volumes in surgery bring better outcomes. The VA National Surgical Quality Improvement Program (NSQIP) is a validated, outcome-based program that prospectively collects clinical data on all major surgical operations in the VA, and builds validated risk-adjustment models that generate, for each hospital and each surgical specialty within a hospital, risk-adjusted outcomes expressed as O/E (observed to expected) ratios for 30-day mortality and morbidity. The O/E ratio has been validated as a reliable comparative measure of the quality of surgical care. Unlike retrospective studies that are based on administrative databases, NSQIP studies have failed to demonstrate a direct relationship between volume and risk-adjusted outcomes of surgery across various specialties. These studies have emphasized that the quality of systems of care was more important than volume in determining the overall quality of surgical care at an institution. High-volume hospitals could still deliver poor care in as much as low-volume hospitals could deliver good care. NSQIP studies have also underscored the major limitations of claims data and administrative databases in the provision of adequate risk-adjustment models that are crucial for volume-outcome studies. Therefore, volume should not be substituted for prospectively monitored and properly risk-adjusted outcomes as a comparative measure of the quality of surgical care. C1 Harvard Univ, Sch Med, Surg Serv, VA Boston Healthcare Syst,Brigham & Womens Hosp, Boston, MA 02132 USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO 80045 USA. RP Khuri, SF (reprint author), Harvard Univ, Sch Med, Surg Serv, VA Boston Healthcare Syst,Brigham & Womens Hosp, 1400 VFW Pkway, Boston, MA 02132 USA. EM shukri.khuri@med.va.gov NR 11 TC 89 Z9 89 U1 0 U2 1 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 OCT PY 2005 VL 29 IS 10 BP 1222 EP 1229 DI 10.1007/s00268-005-7987-6 PG 8 WC Surgery SC Surgery GA 973AH UT WOS:000232494800005 PM 16151664 ER PT J AU Sin, A Murthy, SK Revzin, A Tompkins, RG Toner, M AF Sin, A Murthy, SK Revzin, A Tompkins, RG Toner, M TI Enrichment using antibody-coated microfluidic chambers in shear flow: Model mixtures of human lymphocytes SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE cell affinity chromatography; microfluidic devices; blood cell separation; immobilized antibodies; dynamic cell adhesion ID COUNTERFLOW CENTRIFUGAL ELUTRIATION; CELL-SEPARATION; FRACTIONATION; DYNAMICS; ADHESION; BINDING; DESIGN; SORTER AB Isolation of phenotypically-pure cell subpopulations from heterogeneous cell mixtures such as blood is a difficult yet fundamentally important task. Current techniques such as fluorescent activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) require pre-incubation with antibodies which lead to processing times of at least 15-60 min. In this study, we explored the use of antibody-coated microfluidic chambers to negative deplete undesired cell types, thus obtaining an enriched cell subpopulation at the outlet. We used human lymphocyte cell lines, MOLT-3 and Raji, as a model system to examine the dynamic cell binding behavior on antibody coated surfaces under shear flow. Shear stress ranging between 0.75 and 1.0 dyn/cm(2) was found to provide most efficient separation. Cell adhesion was shown to follow pseudo-first order kinetics, and an anti-CD19 coated (Raji-depletion) device with similar to 2.6 min residence time was demonstrated to produce 100% pure MOLT-3 cells from 50-50 MOLT-3/Raji mixture. We have developed a mathematical model of the separation device based on the experimentally determined kinetic parameters that can be extended to design future separation modules for other cell mixtures. We conclude that we can design microfluidic devices that exploits the kinetics of dynamic cell adhesion to antibody coated surfaces to provide enriched cell subpopulations within minutes of total processing time. (c) 2005 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. FU NIBIB NIH HHS [P41 EB002503] NR 25 TC 59 Z9 60 U1 1 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD SEP 30 PY 2005 VL 91 IS 7 BP 816 EP 826 DI 10.1002/bit.20556 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 962CW UT WOS:000231709600005 PM 16037988 ER PT J AU Fischer, H Sandblom, J Gavazzeni, J Fransson, P Wright, CI Backman, L AF Fischer, H Sandblom, J Gavazzeni, J Fransson, P Wright, CI Backman, L TI Age-differential patterns of brain activation during perception of angry faces SO NEUROSCIENCE LETTERS LA English DT Article DE aging; amygdala; emotion; fMRI; hippocampus; insula cortex ID NEURAL SYSTEMS; EMOTION; AMYGDALA; RESPONSES; EXPRESSION; STIMULI; OLDER; FMRI AB Functional magnetic resonance imaging (fMRI) was used to study age-related differences in the neural circuitry involved in perception of negative facial affect. During scanning, 24 younger and 22 older adults viewed blocks of angry and neutral faces. The fMRI data analysis of the angry versus neutral faces contrast demonstrated greater activation in younger versus older individuals in the right amygdala/hippocampus region, whereas older adults demonstrated greater activation in the right anterior-ventral insula cortex. Hence, normal aging seems to affect specific nodes in the neural network involved in processing negative emotional face information. This age-related change from more subcortical to more cortical involvement could reflect functional compensation within the neural system involved in perception of facial affect, or the fact that older adults process emotional information in a different manner than do young adults. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Karolinska Inst, Neurotec, Div Geriatr Epidemiol, Aging Res Ctr, S-11382 Stockholm, Sweden. Karolinska Hosp, Dept Clin Neurosci, Clin Neurophysiol Sect, S-10401 Stockholm, Sweden. Univ Stockholm, Dept Psychol, S-10691 Stockholm, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Boston, MA USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Max Planck Inst Human Dev, Ctr Lifespan Psychol, Berlin, Germany. RP Fischer, H (reprint author), Karolinska Inst, Neurotec, Div Geriatr Epidemiol, Aging Res Ctr, Olivecronas Vag 4,Box 6401, S-11382 Stockholm, Sweden. EM hakan.fischer@neurotec.ki.se RI Fransson, Peter/M-5679-2014 OI Fransson, Peter/0000-0002-1305-9875 NR 32 TC 60 Z9 63 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 30 PY 2005 VL 386 IS 2 BP 99 EP 104 DI 10.1016/j.neulet.2005.06.002 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 955HG UT WOS:000231215900007 PM 15993537 ER PT J AU Falkowski, PG Katz, ME Milligan, AJ Fennel, K Cramer, BS Aubry, MP Berner, RA Novacek, MJ Zapol, WM AF Falkowski, PG Katz, ME Milligan, AJ Fennel, K Cramer, BS Aubry, MP Berner, RA Novacek, MJ Zapol, WM TI The rise of oxygen over the past 205 million years and the evolution of large placental mammals SO SCIENCE LA English DT Article ID ATMOSPHERIC OXYGEN; PHANEROZOIC TIME; CARBON-CYCLE; RADIATION; BOUNDARY; O-2 AB On the basis of a carbon isotopic record of both marine carbonates and organic matter from the Triassic-Jurassic boundary to the present, we modeled oxygen concentrations over the past 205 million years. Our analysis indicates that atmospheric oxygen approximately doubled over this period, with relatively rapid increases in the early Jurassic and the Eocene. We suggest that the overall increase in oxygen, mediated by the formation of passive continental margins along the Atlantic Ocean during the opening phase of the current Wilson cycle, was a critical factor in the evolution, radiation, and subsequent increase in average size of placental mammals. C1 Rutgers State Univ, Inst Marine & Coastal Sci, New Brunswick, NJ 08901 USA. Rutgers State Univ, Dept Geol Sci, Piscataway, NJ 08854 USA. Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA. Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Falkowski, PG (reprint author), Rutgers State Univ, Inst Marine & Coastal Sci, 71 Dudley Rd, New Brunswick, NJ 08901 USA. EM falko@imcs.rutgers.edu RI Cramer, Benjamin/A-5303-2008; Fennel, Katja/A-7470-2009 OI Fennel, Katja/0000-0003-3170-2331 NR 30 TC 137 Z9 158 U1 6 U2 59 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 SEP 30 PY 2005 VL 309 IS 5744 BP 2202 EP 2204 DI 10.1126/science.1116047 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 970NX UT WOS:000232318000039 PM 16195457 ER PT J AU Koch, M Frazier, J Sodroski, J Wyatt, R AF Koch, M Frazier, J Sodroski, J Wyatt, R TI Characterization of antibody responses to purified HIV-1 gp120 glycoproteins fused with the molecular adjuvant C3d SO VIROLOGY LA English DT Article DE HIV-1; glycoprotein; molecular adjuvant ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; PARTIAL DELETION; RECEPTOR; TRIMERS; IMMUNOGENICITY; FUSION; INFECTION; VACCINE AB The HIV-1 exterior envelope glycoprotein gp120 binds receptor (CD4) and co-receptors (CCR5/CXCR4) and is a major target for neutralizing antibodies. The two functionally conserved regions of gp120 involved in receptor binding are conformational in nature. It is likely that the elicitation of neutralizing antibodies to these targets will benefit by presentation of these sites to the humoral immune system under physiologic conditions. Initially, we investigated the ability of the molecular adjuvant C3d to enhance antibody responses to variant gp120 glycoproteins in phosphate-buffered saline (PBS). We utilized a gp120 variant glycoprotein deleted of N- and C-terminal sequences (gp120 Delta C1/C5) originally designed to eliminate immunodominant, non-neutralizing epitopes and characterized this protein when fused to two C3d elements (gp120 Delta C1/C5(C3d)2). In PBS, the gp120 Delta C1/C5(C3d)2 proteins are able to elicit gp120 binding antibodies more efficiently than gp120 lacking C3d moieties. We then asked if we could observe C3d-enhanced immunogenicity of gp120 in the presence of the classical oil-in-water adjuvant, Ribi. In the presence of the Ribi, which contains the TLR-4 agonist monophospholipid A (MPL), antibodies elicited by the gp120 Delta C1/C5(C3d)2 were of higher titer than those elicited by the identical protein in PBS. To determine if the elicited secondary response was due to a synergy between the C3d repeats and the Ribi, we then inoculated gp120 Delta C1/C5 protein in Ribi and observed that similar titers of anti-gp120 antibodies were elicited in comparison to the gp120 Delta C1/C5(C3d)2 protein also inoculated in Ribi adjuvant. In Ribi, there was a small but consistent increase in gp120-specific antibody titer of a gp120 Delta C1/C5(C3d)2 prime followed by two gp120 Delta C1/C5 boosts compared to three inoculations of either the gp120 Delta C1/C5 proteins or the-gp120 Delta C1/C5(C3d)2 proteins alone. We conclude that the molecular adjuvant C3d demonstrates utility in conditions where physiologic presentation of native protein structures is desired, but may have less benefit in the context of a relatively potent protein adjuvant such as Ribi. C1 NIAID, Vaccine Res Ctr, NIH, Struct Virol Sect, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany. RP Wyatt, R (reprint author), NIAID, Vaccine Res Ctr, NIH, Struct Virol Sect, 40 Convent Dr,Bldg 40, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov FU NIAID NIH HHS [AI42719-02] NR 36 TC 11 Z9 12 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 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2005 VL 340 IS 2 BP 277 EP 284 DI 10.1016/j.virol.2005.06.034 PG 8 WC Virology SC Virology GA 969FB UT WOS:000232217800011 PM 16051303 ER PT J AU Block, SD Billings, JA AF Block, SD Billings, JA TI Becoming a physician - Learning from dying SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Block, SD (reprint author), Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. NR 3 TC 21 Z9 21 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 29 PY 2005 VL 353 IS 13 BP 1313 EP 1315 DI 10.1056/NEJMp048171 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 968FB UT WOS:000232146200001 PM 16192474 ER PT J AU Koehler, JE Duncan, LM Harris, NL Basgoz, N AF Koehler, JE Duncan, LM Harris, NL Basgoz, N TI A 56-year-old man with fever and axillary lymphadenopathy - Bartonella henselae infection (cat scratch disease) in an immunocompromised host. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BACILLARY ANGIOMATOSIS; DOMESTIC CATS; RISK-FACTORS; EPIDEMIOLOGY; RECOMMENDATIONS; TRANSMISSION; PREVALENCE; RESERVOIR; PELIOSIS C1 Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Koehler, JE (reprint author), Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. NR 30 TC 15 Z9 15 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 SEP 29 PY 2005 VL 353 IS 13 BP 1387 EP 1394 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 968FB UT WOS:000232146200012 PM 16192484 ER PT J AU Carabello, BA AF Carabello, BA TI Vasodilators in aortic regurgitation - Where is the evidence of their effectiveness? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ASYMPTOMATIC PATIENTS; MITRAL REGURGITATION; VALVE-REPLACEMENT; NIFEDIPINE; INSUFFICIENCY; PERFORMANCE; THERAPY C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Carabello, BA (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 13 TC 11 Z9 11 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 SEP 29 PY 2005 VL 353 IS 13 BP 1400 EP 1402 DI 10.1056/NEJMe058213 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 968FB UT WOS:000232146200015 PM 16192487 ER PT J AU Oh, DH Yeh, K AF Oh, DH Yeh, K TI Differentiating human keratinocytes are deficient in p53 but retain global nucleotide excision repair following ultraviolet radiation SO DNA REPAIR LA English DT Article DE DNA repair; ultraviolet rays; thymine dimer; keratinocyte; differentiation ID CYCLOBUTANE PYRIMIDINE DIMERS; HUMAN-SKIN INVIVO; GROUP-C GENE; DNA-DAMAGE; GENOMIC REPAIR; UV-IRRADIATION; EPIDERMAL-KERATINOCYTES; HUMAN FIBROBLASTS; TUMOR-SUPPRESSOR; BINDING-FACTOR AB Terminally differentiating keratinocytes constitute the predominant cell type within the skin epidermis and play an important role in the overall photobiology of human skin following ultraviolet radiation. However, the DNA repair capacity of differentiating keratinocytes is unclear, and little is known regarding how such repair activity is regulated in these cells. We systematically compared the global genomic nucleotide excision repair response of cultured undifferentiated human keratinocytes to those that were allowed to differentiate in 1.2 mM Ca2+, in some cases supplemented with phorbol ester or Vitamin C. Differentiated cells ceased replication and expressed typical markers of differentiation. Following ultraviolet radiation, keratinocytes that were differentiated up to 12 days removed cyclobutane pyrimidine dimers and pyrimidine(6,4)pyrimidone photoproducts from the global genome as efficiently as undifferentiated cells. However, following the onset of calcium-induced differentiation, basal levels of p53 were nearly undetectable by 12 days of differentiation when global repair activity was unaffected. Following ultraviolet radiation, induction of p53 following ultraviolet radiation was abrogated by 6 days of calcium-induced differentiation. Basal levels of mRNA encoding the DNA damage recognition proteins, XPC and DDB2, were relatively insensitive to differentiation and p53 levels. However, following ultraviolet radiation, inductions of mRNA encoding the DNA damage recognition proteins, DDB2 and XPC, were differentially affected by differentiation. Rapid loss of DDB2 mRNA induction was associated with differentiation, while XPC mRNA induction diminished more slowly with differentiation. These results indicate that human keratinocytes preserve global nucleotide excision repair as well as expression of genes encoding key DNA damage recognition proteins well into the terminal differentiation process. perhaps using mechanisms other than p53. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Dermatol Serv 190, San Francisco, CA 94121 USA. RP Oh, DH (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. EM dennisoh@itsa.ucsf.edu NR 63 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 28 PY 2005 VL 4 IS 10 BP 1149 EP 1159 DI 10.1016/j.dnarep.2005.06.004 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 972BP UT WOS:000232429100011 PM 16043423 ER PT J AU Chen, IA Salehi-Ashtiani, K Szostak, JW AF Chen, IA Salehi-Ashtiani, K Szostak, JW TI RNA catalysis in model protocell vesicles SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID FATTY-ACID VESICLES; HAMMERHEAD RIBOZYME; GROUP SELECTION; MONOCARBOXYLIC ACIDS; ENERGY-TRANSFER; MAGNESIUM; EVOLUTION; MEMBRANES; GROWTH; LIFE AB We are engaged in a long-term effort to synthesize chemical systems capable of Darwinian evolution, based on the encapsulation of self-replicating nucleic acids in self-replicating membrane vesicles. Here, we address the issue of the compatibility of these two replicating systems. Fatty acids form vesicles that are able to grow and divide, but vesicles composed solely of fatty acids are incompatible with the folding and activity of most ribozymes, because low concentrations of divalent cations (e.g., Mg2+) cause fatty acids to precipitate. Furthermore, vesicles that grow and divide must be permeable to the cations and substrates required for internal metabolism. We used a mixture of myristoleic acid and its glycerol monoester to construct vesicles that were Mg2+-tolerant and found that Mg2+ cations can permeate the membrane and equilibrate within a few minutes. In vesicles encapsulating a hammerhead ribozyme, the addition of external Mg2+ led to the activation and self-cleavage of the ribozyme molecules. Vesicles composed of these amphiphiles grew spontaneously through osmotically driven competition between vesicles, and further modification of the membrane composition allowed growth following mixed micelle addition. Our results show that membranes made from simple amphiphiles can form vesicles that are stable enough to retain encapsulated RNAs in the presence of divalent cations, yet dynamic enough to grow spontaneously and allow the passage of Mg2+ and mononucleotides without specific macromolecular transporters. This combination of stability and dynamics is critical for building model protocells in the laboratory and may have been important for early cellular evolution. C1 Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243 FU NIGMS NIH HHS [T32 GM007753, T32 GM007753-21, T32 GM008313, T32 GM008313-11, T32-GM07753, T32-GM08313] NR 48 TC 98 Z9 102 U1 4 U2 41 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 28 PY 2005 VL 127 IS 38 BP 13213 EP 13219 DI 10.1021/ja051784p PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 968OC UT WOS:000232170800049 PM 16173749 ER PT J AU Nesta, F Leyne, M Yosefy, C Simpson, C Dai, D Marshall, JE Hung, J Slaugenhaupt, SA Levine, RA AF Nesta, F Leyne, M Yosefy, C Simpson, C Dai, D Marshall, JE Hung, J Slaugenhaupt, SA Levine, RA TI New locus for autosomal dominant mitral valve prolapse on chromosome 13 - Clinical insights from genetic studies SO CIRCULATION LA English DT Article; Proceedings Paper CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc DE echocardiography; genetics; mitral valve ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; MULTILOCUS LINKAGE ANALYSIS; GLYCOSAMINOGLYCAN CONTENT; SELECTIVE ELEVATION; CONNECTIVE-TISSUE; MARFAN-SYNDROME; COLLAGEN GENES; LOD SCORES; FOLLOW-UP; DIAGNOSIS AB Background - Mitral valve prolapse ( MVP) is a common disorder associated with mitral regurgitation, endocarditis, heart failure, and sudden death. To date, 2 MVP loci have been described, but the defective genes have yet to be discovered. In the present study, we analyzed a large family segregating MVP, and identified a new locus, MMVP3. This study and others have enabled us to explore mitral valve morphological variations of currently uncertain clinical significance. Methods and Results - Echocardiograms and blood samples were obtained from 43 individuals who were classified by the extent and pattern of displacement. Genotypic analyses were performed with polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 13q31.3- q32.1, with a peak nonparametric linkage score of 18.41 ( P < 0.0007). Multipoint parametric analysis gave a logarithm of odds score of 3.17 at marker D13S132. Of the 6 related individuals with mitral valve morphologies not meeting diagnostic criteria but resembling fully developed forms, 5 carried all or part of the haplotype linked to MVP. Conclusions - The mapping of a new MVP locus to chromosome 13 confirms the observed genetic heterogeneity and represents an important step toward gene identification. Furthermore, the genetic analysis provides clinical lessons with regard to previously nondiagnostic morphologies. In the familial context, these may represent early expression in gene carriers. Early recognition of gene carriers could potentially enhance the clinical evaluation of patients at risk of full expression, with the ultimate aim of developing interventions to reduce progression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Levine, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, 55 Fruit St YWK5068, Boston, MA 02114 USA. EM rlevine@partners.org FU NHLBI NIH HHS [R01-HL-38176, K24-HL-67434] NR 58 TC 67 Z9 69 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 27 PY 2005 VL 112 IS 13 BP 2022 EP 2030 DI 10.1161/CIRCULATIONAHA104.516930 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 967ST UT WOS:000232112200017 PM 16172273 ER PT J AU Mavrakis, AN Halpern, EF Barker, FG Gonzalez, RG Henson, JW AF Mavrakis, AN Halpern, EF Barker, FG Gonzalez, RG Henson, JW TI Diagnostic evaluation of patients with a brain mass as the presenting manifestation of cancer SO NEUROLOGY LA English DT Article ID PRIMARY TUMOR; CEREBRAL METASTASES; CHEST RADIOGRAPH; TOMOGRAPHY; ORIGIN AB Background: Patients with a newly detected brain mass and no history of cancer often undergo extensive diagnostic testing in search of a systemic primary neoplasm prior to selection of a biopsy site, potentially leading to unnecessary expense and delay. We sought patterns in the evaluation of these patients to allow rapid selection of a biopsy site. Methods: We compared the diagnostic evaluation of 176 patients with newly detected brain masses who were ultimately determined to have a metastatic or primary lesion. Results: In 88 patients presenting with brain metastasis, lung cancer was markedly overrepresented as a primary tumor, occurring in 82% of patients. Brain MRI and chest CT together identified the site for diagnostic biopsy in all except for two of the 176 patients. One-half of the patients with metastasis had brain biopsy as the primary diagnostic procedure, with 80% undergoing a craniotomy rather than needle biopsy. The initial management decision in the majority of metastasis patients was whether to perform a craniotomy for resection of tumor. Whereas patients with single and cerebellar lesions were most likely to undergo craniotomy, the extent of systemic disease did not affect the decision to recommend a neurosurgical procedure. The average time to biopsy for patients with metastatic and primary tumors was 4.7 days and 6.0 days. In this retrospective population, we estimated that evaluation with brain MRI and chest CT, followed by an early neurosurgical decision, could reduce the time to diagnosis by at least 10%. Conclusions: Chest CT and brain MRI, if used together as initial diagnostic studies, would have identified a biopsy site in 97% of patients with a newly detected brain mass. C1 Massachusetts Gen Hosp, Ctr Neuroonocl, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Ctr Neuroonocl, Yawkey 9 E,55 Fruit St, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 12 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 27 PY 2005 VL 65 IS 6 BP 908 EP 911 DI 10.1212/01.wnl.0000176059.21455.76 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 967RV UT WOS:000232109800026 PM 16186533 ER PT J AU Colleoni, M Li, SG Gelber, RD Price, KN Coates, AS Castiglione-Gertsch, M Goldhirsch, A AF Colleoni, M Li, SG Gelber, RD Price, KN Coates, AS Castiglione-Gertsch, M Goldhirsch, A CA Int Breast Canc Study Grp TI Relation between chemotherapy dose, oestrogen receptor expression, and body-mass index SO LANCET LA English DT Article ID BREAST-CANCER; OBESITY AB Clinicians often reduce chemotherapy doses when treating obese patients because of concerns about overdosing. We assessed dose-response according to body-mass index (BMI) and oestrogen receptor (ER) expression of the primary tumour in premenopausal patients with node-positive breast cancer treated with classical CMF (cyclophosphamide, methotrexate, and 5-fluorouracil). Obese patients were significantly more likely to receive a lower chemotherapy dose (<85% of expected dose) for the first course than were those with normal or intermediate BMI (39% vs 16%, p<0.0001). For obese patients and for the total population, reducing the dose of chemotherapy was associated with a significantly worse outcome for the ER-negative cohort (total population hazards ratio >= 85% vs <85% 0.68 [95% CI 0.54-0.86] for disease free survival; 0.72 [0.56-0.94] for overall survival) but not for the ER-positive cohort (1.16 [0.97-1.40] for disease-free survival; 1.16 [0.94-1.44] for overall survival) [interaction p values=0.0001 for disease-free survival and 0.0019 for overall survival]. Our findings suggest that for women with ER-absent or ER-low tumours, reduction in chemotherapy dose should be avoided. C1 European Inst Oncol, Div Med Oncol, I-20141 Milan, Italy. Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Tehcnol Res Fdn, Boston, MA USA. Univ Sydney, Sydney, NSW 2006, Australia. Canc Council Australia, Sydney, NSW, Australia. IBCSG Coordinating Ctr, Bern, Switzerland. Oncol Inst So Switzerland, Lugano, Switzerland. RP Colleoni, M (reprint author), European Inst Oncol, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM marco.colleoni@ieo.it FU NCI NIH HHS [CA-75362] NR 5 TC 72 Z9 72 U1 1 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 24 PY 2005 VL 366 IS 9491 BP 1108 EP 1110 DI 10.1016/S0140-6736(05)67110-3 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 967TL UT WOS:000232114000029 PM 16182899 ER PT J AU Yu, XG Lichterfeld, M Perkins, B Kalife, E Mui, S Chena, JP Cheng, M Kang, WZ Alter, G Brander, C Walker, BD Altfeld, M AF Yu, XG Lichterfeld, M Perkins, B Kalife, E Mui, S Chena, JP Cheng, M Kang, WZ Alter, G Brander, C Walker, BD Altfeld, M CA Boston HIV Study Grp TI High degree of inter-clade cross-reactivity of HIV-1-specific T cell responses at the single peptide level SO AIDS LA English DT Article DE HIV-1; CD8 T cell response; inter-clade cross-reactivity; entropy; inter-clade homology ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-RESPONSES; HIV-1 INFECTION; RECOGNITION; LYMPHOCYTES; VACCINE; EPITOPES; VIREMIA; DIVERSITY; REGIONS AB Objectives: To determine HIV-1-specific T cell responses in clade B infected individuals recognizing the clade A, Band C consensus sequences in order to assess the degree of inter-clade cross-reactivity of these immune responses at the single epitope level. Methods: HIV-1-specific T cell responses were assessed cross-sectionally in 27 chronically HIV-1-infected individuals from a population infected mainly with clade B viral strains, using an interferon-gamma Elispot assay with a total of 1230 overlapping peptides spanning the entire amino acid sequence of the clade A, B and C 2001 consensus sequences. Results: No significant difference was observed between the total magnitude or breadth of T cell responses recognizing either the clade A, B or C consensus sequences. However, at the single peptide level, 194 T cell responses were identified that recognized only one of the three different clade-specific peptide variants (A : B : C, 34 : 105 : 55), 125 T cell responses recognized two of the three peptide variants (AB : AC : BC, 71 : 15 : 39) and 166 T cell responses (34%) were cross-reactive with all three different peptide variants. Peptides recognized in all three consensus sequence variants had a significantly lower entropy (P < 0.0001) and a significantly higher inter-clade homology (P < 0.0001). Conclusions: Viral epitopes within regions of low HIV-1 clade B diversity and high inter-clade homology can be recognized in the clade A, B and C variants and indicate a wide degree of cross-isolate and cross-clade recognition by HIV-1-specific T cells. These regions may therefore be of particular relevance for the design of HIV-1 vaccines. (c) 2005 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Chinese Ctr Dis Control, Beijing, Peoples R China. Fourth Mil Med Univ, Xian, Peoples R China. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Yu, XG (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Rm 6624, Boston, MA 02129 USA. EM xyu@partners.org NR 26 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 23 PY 2005 VL 19 IS 14 BP 1449 EP 1456 DI 10.1097/01.aids.0000183126.32077.c8 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 970MN UT WOS:000232314400002 PM 16135897 ER PT J AU Orkin, SH AF Orkin, SH TI Chipping away at the embryonic stem cell network SO CELL LA English DT Editorial Material ID GENE-EXPRESSION AB Critical transcription factors, notably OCT4, SOX2, and NANOG, are necessary to maintain self-renewal and pluripotency, two properties characteristic of embryonic stem (ES) cells. By analyzing the genome-wide localization of these factors at promoter regions in human ES cells, Boyer et al. (2005) demonstrate frequent promoter cooccupancy at numerous target genes. As they discuss in this issue of Cell, their findings indicate the presence of a complex network of autoregulatory and feedforward loops in human ES cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 27 Z9 28 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 23 PY 2005 VL 122 IS 6 BP 828 EP 830 DI 10.1016/j.cell.2005.09.002 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 967ZL UT WOS:000232130200006 PM 16179251 ER PT J AU Oka, T Vasile, E Penman, M Novina, CD Dykxhoorn, DM Ungar, D Hughson, FM Krieger, M AF Oka, T Vasile, E Penman, M Novina, CD Dykxhoorn, DM Ungar, D Hughson, FM Krieger, M TI Genetic analysis of the subunit organization and function of the conserved oligomeric golgi (COG) complex - Studies of Cog5- and Cog7-deficient mammalian cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; HAMSTER-CELL MUTANTS; RECEPTOR-MEDIATED ENDOCYTOSIS; ENDOPLASMIC-RETICULUM; PROTEIN COMPLEX; SACCHAROMYCES-CEREVISIAE; RETROGRADE TRANSPORT; VESICLE DOCKING; COAT PROTEINS; SNARE TLG1P AB The conserved oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein involved in Golgi-associated membrane trafficking and glycoconjugate synthesis. We have analyzed the structure and function of COG using Cog1 or Cog2 null Chinese hamster ovary cell mutants, fibroblasts from a patient with Cog7-deficient congenital disorders of glycosylation, and stable Cog5-deficient HeLa cells generated by RNA interference. Although the dilation of some Golgi cisternae in Cog5-deficient cells resembled that observed in Cog1- or Cog2-deficient cells, their global glycosylation defects (less severe) and intracellular processing and function of low density lipoprotein receptors (essentially normal) differed from Cog1- and Cog2-deficient cells. Immunoblotting, gel filtration, and immunofluorescence microscopy analyses of the COG-deficient cells and cell extracts indicated that 1) Cog2-4 and Cog5-7 form stable subcomplexes, 2) Cog1 mediates Golgi association of a Cog2-4 plus Cog8 subcomplex, 3) Cog8 associates stably with both Cog5-7 and Cog1-4 subcomplexes, and thus 4) Cog8 helps assemble the Cog1-4 and Cog5-7 subcomplexes into the complete COG complex. This model of the subunit organization of COG is in excellent agreement with in vitro data presented in an accompanying paper (Ungar, D., Oka, T., Vasile, E., Krieger, M., and Hughson, F. M. (2005) J. Biol. Chem. 280, 32729-32735). Only one or two of the seven Cog1- or Cog2-dependent Golgi membrane proteins called GEARs are also sensitive to Cog5 or Cog7 deficiency, indicating that the COG subunits play distinctive roles in controlling Golgi structure and function. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 8128582, Japan. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Harvard Univ, Sch Med, Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Krieger, M (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA. EM krieger@mit.edu RI Ungar, Daniel/A-5302-2012; Dykxhoorn, Derek/D-1357-2015 FU NIGMS NIH HHS [GM59115] NR 58 TC 50 Z9 52 U1 1 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 23 PY 2005 VL 280 IS 38 BP 32736 EP 32745 DI 10.1077/jbc.M505558200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 964ZU UT WOS:000231920300024 PM 16051600 ER PT J AU Calautti, E Li, J Saoncella, S Brissette, JL Goetinck, PF AF Calautti, E Li, J Saoncella, S Brissette, JL Goetinck, PF TI Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus death SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CELL ADHESION; NF-KAPPA-B; GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; E-CADHERIN; TERMINAL DIFFERENTIATION; PATHWAY; EPIDERMIS; ACTIVATION; SURVIVAL AB Signaling pathways regulating the differentiation program of epidermal cells overlap widely with those activated during apoptosis. How differentiating cells remain protected from premature death, however, is still poorly defined. We show here that the phosphoinositide 3-kinase ( PI3K)/ Akt pathway is activated at early stages of mouse keratinocyte differentiation both in culture and in the intact epidermis in vivo. Expression of active Akt in keratinocytes promotes growth arrest and differentiation, whereas pharmacological blockade of PI3K inhibits the expression of "late" differentiation markers and leads to death of cells that would otherwise differentiate. Mechanistically, the activation of the PI3K/Akt pathway in keratinocyte differentiation depends on the activity of the epidermal growth factor receptor and Src families of tyrosine kinases and the engagement of E- cadherin- mediated adhesion. During this process, PI3K associates increasingly with cadherin- catenin protein complexes bearing tyrosine phosphorylated YXXM motifs. Thus, the PI3K signaling pathway regulates the choice between epidermal cell differentiation and death at the cross-talk between tyrosine kinases and cadherin- associated catenins. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Calautti, E (reprint author), Osped Civile Venezia, Epithelial Stem Cell Res Ctr, Veneto Eye Bank Fdn, Castello 6777, I-30122 Venice, Italy. EM enzo.calautti@cbrc2.mgh.harvard.edu OI CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NIAMS NIH HHS [AR454284]; NICHD NIH HHS [HD-37490]; Telethon [TCP06001] NR 41 TC 105 Z9 105 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 SEP 23 PY 2005 VL 280 IS 38 BP 32856 EP 32865 DI 10.1074/jbc.M506119200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 964ZU UT WOS:000231920300039 PM 16036919 ER PT J AU Peterfy, M Phan, J Reue, K AF Peterfy, M Phan, J Reue, K TI Alternatively spliced lipin isoforms exhibit distinct expression pattern, subcellular localization, and role in adipogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE-C-BETA; TRANSCRIPTION FACTOR; MESSENGER-RNA; INSULIN; GENE; PROTEIN; LIPODYSTROPHY; MUTATION; OBESITY; CELLS AB We recently identified mutations in the Lpin1 ( lipin) gene to be responsible for lipodystrophy in the fatty liver dystrophy (fld) mouse strain. Previous studies revealed that lipin plays a critical role in adipogenesis, explaining the adipose-deficient phenotype of the fld mouse. In the current study, we demonstrate that alternative mRNA splicing generates two lipin isoforms, lipin-alpha and lipin-beta, which are differentially expressed during adipocyte differentiation. Lipin-alpha expression peaks at day 2 of 3T3-L1 cell differentiation, after which its levels gradually decrease. In contrast, lipin-beta expression is transiently elevated at 10 h, followed by a drop to background levels at 20 h and a gradual increase between days 2 and 6 of differentiation. The two lipin isoforms also exhibit differences in subcellular localization. Lipin-alpha is predominantly nuclear, whereas lipin-beta is primarily located in the cytoplasm of 3T3-L1 adipocytes, suggesting distinct cellular functions. Using primary mouse embryonic fibroblasts expressing either lipin-alpha or lipin-alpha, we demonstrate functional differences between the two isoforms. Whereas effect of lipin-beta expression is the induction of lipogenic genes. In vivo, overexpression of lipin-beta specifically in mature adipocytes leads to elevated expression of lipogenic genes and adipocyte hypertrophy, confirming a role of lipin-beta in the regulation of lipogenesis. In conclusion, our data suggest that the two lipin isoforms have distinct, but complementary, functions in adipogenesis, with lipin-alpha playing a primary role in differentiation and lipin-beta being predominantly involved in lipogenesis. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Reue, K (reprint author), 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. EM reuek@ucla.edu FU NHLBI NIH HHS [HL24841]; NIGMS NIH HHS [GM08042] NR 30 TC 138 Z9 147 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 23 PY 2005 VL 280 IS 38 BP 32883 EP 32889 DI 10.1074/jbc.M503885200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 964ZU UT WOS:000231920300042 PM 16049017 ER PT J AU Wang, XJ Yu, JJ Sreekumar, A Varambally, S Shen, RL Giacherio, D Mehra, R Montie, JE Pienta, KJ Sanda, MG Kantoff, PW Rubin, MA Wei, JT Ghosh, D Chinnaiyan, AM AF Wang, XJ Yu, JJ Sreekumar, A Varambally, S Shen, RL Giacherio, D Mehra, R Montie, JE Pienta, KJ Sanda, MG Kantoff, PW Rubin, MA Wei, JT Ghosh, D Chinnaiyan, AM TI Autoantibody signatures in prostate cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENE-EXPRESSION ANALYSIS; HUMORAL IMMUNE-RESPONSE; METHYLACYL-COA RACEMASE; MOLECULAR-MARKER; ANTIBODIES; ANTIGENS; IDENTIFICATION; SERA AB BACKGROUND: New biomarkers, such as autoantibody signatures, may improve the early detection of prostate cancer. METHODS: With a phage-display library derived from prostate-cancer tissue, we developed and used phage protein microarrays to analyze serum samples from 119 patients with prostate cancer and 138 controls, with the samples equally divided into training and validation sets. A phage-peptide detector that was constructed from the training set was evaluated on an independent validation set of 128 serum samples (60 from patients with prostate cancer and 68 from controls). RESULTS: A 22-phage-peptide detector had 88.2 percent specificity (95 percent confidence interval, 0.78 to 0.95) and 81.6 percent sensitivity (95 percent confidence interval, 0.70 to 0.90) in discriminating between the group with prostate cancer and the control group. This panel of peptides performed better than did prostate-specific antigen (PSA) in distinguishing between the group with prostate cancer and the control group (area under the curve for the autoantibody signature, 0.93; 95 percent confidence interval, 0.88 to 0.97; area under the curve for PSA, 0.80; 95 percent confidence interval, 0.71 to 0.88). Logistic-regression analysis revealed that the phage-peptide panel provided additional discriminative power over PSA (P<0.001). Among the 22 phage peptides used as a detector, 4 were derived from in-frame, named coding sequences. The remaining phage peptides were generated from untranslated sequences. CONCLUSIONS: Autoantibodies against peptides derived from prostate-cancer tissue could be used as the basis for a screening test for prostate cancer. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Dept Pathol & Urol, 1301 Catherine St,MSI 4237, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012; Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [R01 CA8241901-A1, 5P30CA46592, P50 CA69568, UO1CA111275]; NIGMS NIH HHS [R01 GM072007, R01 GM072007-03, R01GM72007-01] NR 33 TC 383 Z9 414 U1 1 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 22 PY 2005 VL 353 IS 12 BP 1224 EP 1235 DI 10.1056/NEJMoa051931 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 966DS UT WOS:000232000400006 PM 16177248 ER PT J AU Crocker, JT Polisson, RP Mueller, PR Harris, NL Duncan, LM AF Crocker, JT Polisson, RP Mueller, PR Harris, NL Duncan, LM TI Case 29-2005: A 68-year-old man with periorbital swelling, rash, and weakness - Dermatomyositis, due to diffuse large-B-cell lymphoma of the spleen. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MALIGNANT-LYMPHOMA; POLYMYOSITIS; DISEASE; MYOPATHIES; DISORDERS; CANCER C1 Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Crocker, JT (reprint author), Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. NR 30 TC 6 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 22 PY 2005 VL 353 IS 12 BP 1275 EP 1284 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 966DS UT WOS:000232000400013 PM 16177254 ER PT J AU Richardson, PG Boral, AL Anderson, KC AF Richardson, PG Boral, AL Anderson, KC TI Bortezomib in multiple myeloma (vol 352, pg 2487, 2005) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Correction C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 22 PY 2005 VL 353 IS 12 BP 1297 EP 1298 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 966DS UT WOS:000232000400025 ER PT J AU Moses, H Dorsey, ER Matheson, DHM Thier, SO AF Moses, H Dorsey, ER Matheson, DHM Thier, SO TI Financial anatomy of biomedical research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CENTERS AB Context Public and private financial support of biomedical research have increased over the past decade. Few comprehensive analyses of the sources and uses of funds are available. This results in inadequate information on which to base investment decisions because not all sources allow equal latitude to explore hypotheses having scientific or clinical importance and creates a barrier to judging the value of research to society. Objective To quantify funding trends from 1994 to 2004 of basic, translational, and clinical biomedical research by principal sponsors based in the United States. Design Publicly available data were compiled for the federal, state, and local governments; foundations; charities; universities; and industry. Proprietary (by subscription but openly available) databases were used to supplement public sources. Main Outcome Measures Total actual research spending, growth rates, and type of research with inflation adjustment. Results Biomedical research funding increased from $37.1 billion in 1994 to $94.3 billion in 2003 and doubled when adjusted for inflation. Principal research sponsors in 2003 were industry (57%) and the National Institutes of Health (28%). Relative proportions from all public and private sources did not change. Industry sponsorship of clinical trials increased from $4.0 to $14.2 billion (in real terms) while federal proportions devoted to basic and applied research were unchanged. The United States spent an estimated 5.6% of its total health expenditures on biomedical research, more than any other country, but less than 0.1% for health services research. From an economic perspective, biotechnology and medical device companies were most productive, as measured by new diagnostic and therapeutic devices per dollar of research and development cost. Productivity declined for new pharmaceuticals. Conclusions Enhancing research productivity and evaluation of benefit are pressing challenges, requiring (1) more effective translation of basic scientific knowledge to clinical application; (2) critical appraisal of rapidly moving scientific areas to guide investment where clinical need is greatest, not only where commercial opportunity is currently perceived; and (3) more specific information about sources and uses of research funds than is generally available to allow informed investment decisions. Responsibility falls on industry, government, and foundations to bring these changes about with a longer-term view of research value. C1 Aler Inst, N Garden, VA 22959 USA. Boston Consulting Grp Inc, Bethesda, MD USA. Massachusetts Gen Hosp, Dept Med & Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Moses, H (reprint author), Aler Inst, POB 150, N Garden, VA 22959 USA. EM hm@alerion.us NR 46 TC 243 Z9 247 U1 2 U2 33 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 21 PY 2005 VL 294 IS 11 BP 1333 EP 1342 DI 10.1001/jama.294.11.1333 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 965YW UT WOS:000231987800006 PM 16174691 ER PT J AU Yeo, Y Bellas, E Firestone, W Langer, R Kohane, DS AF Yeo, Y Bellas, E Firestone, W Langer, R Kohane, DS TI Complex coacervates for thermally sensitive controlled release of flavor compounds SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE complex coacervation; gelatin-gum Arabic; flavor oil; frozen foods; heat-triggered release; controlled delivery ID MICROENCAPSULATION; OIL; PARTICLES AB To improve the appeal of frozen baked foods upon heating, we have encapsulated flavor oil in complex coacervate microcapsules using gelatin and gum Arabic. Variation of polyion concentrations and homogenization rate affected particle morphology, size distribution, and oil release upon heating. Release of the oil from formulations was determined by a simple spectroscopic method based on separation of oil labeled with a lipophilic dye from unaffected particles. When heated to 100 degrees C or higher, univesicular microcapsules (prepared with a lower homogenization rate) released almost all of the encapsulated oil, while multivesicular microcapsules (produced by high homogenization rates) resulted had lesser degrees of release. The oil remained encapsulated during 4 weeks of storage at 4 and -20 degrees C (freezing and thawing) but was released by exposure to 100 mM NaCl at room temperature. When particles were cooled after releasing their oil content, the oil was re-encapsulated. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. RP Kohane, DS (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM00684] NR 19 TC 90 Z9 94 U1 8 U2 53 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP 21 PY 2005 VL 53 IS 19 BP 7518 EP 7525 DI 10.1021/jf0507947 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 964QP UT WOS:000231895900024 PM 16159181 ER PT J AU Giovannucci, E Ogino, S AF Giovannucci, E Ogino, S TI DNA methylation, field effects, and colorectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PROMOTER HYPERMETHYLATION; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; BARRETTS-ESOPHAGUS; CLONAL EVOLUTION; TUMOR-SUPPRESSOR; SPORADIC COLON; DIETARY-FOLATE; RAS MUTATIONS; K-RAS; REPAIR C1 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,Dept Med, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Ctr, Canc Epidemiol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Bldg 11,Rm 331A,665 Huntington Ave, Boston, MA 02115 USA. EM egiovann@hsph.harvard.edu NR 27 TC 54 Z9 54 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 21 PY 2005 VL 97 IS 18 BP 1317 EP 1319 DI 10.1093/jnci/dji305 PG 3 WC Oncology SC Oncology GA 969YV UT WOS:000232273000001 PM 16174847 ER PT J AU Jiang, HY Wang, B Xu, XG Suit, HD Paganetti, H AF Jiang, HY Wang, B Xu, XG Suit, HD Paganetti, H TI Simulation of organ-specific patient effective dose due to secondary neutrons in proton radiation treatment SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MONTE-CARLO SIMULATIONS; MAN ANATOMICAL MODEL; VIP-MAN; CONVERSION COEFFICIENTS; THERAPY; DISTRIBUTIONS; TOOLKIT; GEANT4; CODE AB Cancer patients undergoing radiation treatment are exposed to high doses to the target (tumour), intermediate doses to adjacent tissues and low doses from scattered radiation to all parts of the body. In the case of proton therapy, secondary neutrons generated in the accelerator head and inside the patient reach many areas in the patient body. Due to the improved efficacy of management of cancer patients, the number of long term survivors post-radiation treatment is increasing substantially. This results in concern about the risk of radiation-induced cancer appearing at late post-treatment times. This paper presents a case study to determine the effective dose from secondary neutrons in patients undergoing proton treatment. A whole-body patient model, VIP-Man, was employed as the patient model. The geometry dataset generated from studies made on VIP-Man was implemented into the GEANT4 Monte Carlo code. Two proton treatment plans for tumours in the lung and paranasal sinus were simulated. The organ doses and ICRP-60 radiation and tissue weighting factors were used to calculate the effective dose. Results show whole body effective doses for the two proton plans of 0.162 Sv and 0.0266 Sv, respectively, to which the major contributor is due to neutrons from the proton treatment nozzle. There is a substantial difference among organs depending on the treatment site. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Rensselaer Polytech Inst, Troy, NY 12180 USA. RP Jiang, HY (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA 21239] NR 24 TC 84 Z9 85 U1 0 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2005 VL 50 IS 18 BP 4337 EP 4353 DI 10.1088/0031-9155/50/18/007 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 972BC UT WOS:000232427800007 PM 16148397 ER PT J AU Yu, LQ Haverty, PM Mariani, J Wang, YM Shen, HY Schwarzschild, MA Weng, ZP Chen, JF AF Yu, LQ Haverty, PM Mariani, J Wang, YM Shen, HY Schwarzschild, MA Weng, ZP Chen, JF TI Genetic and pharmacological inactivation of adenosine A(2A) receptor reveals an Egr-2-mediated transcriptional regulatory network in the mouse striatum SO PHYSIOLOGICAL GENOMICS LA English DT Article DE SCH-58261; microarray; A(2A) receptor antagonist; A(2A) receptor knockout; promotor analysis ID FACTOR-BINDING SITES; C-FOS EXPRESSION; PARKINSONS-DISEASE; DOPAMINE D-1; MICE LACKING; INDUCED EXCITOTOXICITY; DNA MICROARRAYS; BASAL GANGLIA; IDENTIFICATION; ANTAGONISTS AB The adenosine A(2A) receptor (A(2A)R) is highly expressed in the striatum, where it modulates motor and emotional behaviors. We used both microarray and bioinformatics analyses to compare gene expression profiles by genetic and pharmacological inactivation of A(2A)R and inferred an A(2A)R-controlled transcription network in the mouse striatum. A comparison between vehicle (VEH)-treated A(2A)R knockout (KO) mice (A(2A)R KO-VEH) and wild-type (WT) mice (WT-VEH) revealed 36 upregulated genes that were partially mimicked by treatment with SCH-58261 (SCH; an A(2A)R antagonist) and 54 downregulated genes that were not mimicked by SCH treatment. We validated the A(2A)R as a specific drug target for SCH by comparing A(2A)R KO-SCH and A(2A)R KO-VEH groups. The unique downregulation effect of A(2A)R KO was confirmed by comparing A(2A)R KO-SCH with WT-SCH gene groups. The distinct striatal gene expression profiles induced by A(2A)R KO and SCH should provide clues to the molecular mechanisms underlying the different phenotypes observed after genetic and pharmacological inactivation of A(2A)R. Furthermore, bioinformatics analysis discovered that Egr-2 binding sites were statistically overrepresented in the proximal promoters of A(2A)R KO-affected genes relative to the unaffected genes. This finding was further substantiated by the demonstration that the Egr-2 mRNA level increased in the striatum of both A(2A)R KO and SCH-treated mice and that striatal Egr-2 binding activity in the promoters of two A(2A)R KO-affected genes was enhanced in A(2A)R KO mice as assayed by chromatin immunoprecipitation. Taken together, these results strongly support the existence of an Egr-2-directed transcriptional regulatory network controlled by striatal A(2A)Rs. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Bioinformat Program, Boston, MA 02118 USA. Boston Univ, Dept Biomed Engn, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Weng, ZP (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,E301, Boston, MA 02118 USA. EM zhiping@bu.edu; chenjf@bu.edu FU NHGRI NIH HHS [HG-03110]; NIDA NIH HHS [DA-019362, DA-13508]; NIEHS NIH HHS [ES-10804]; NIGMS NIH HHS [GM-066401]; NINDS NIH HHS [NS-41083] NR 93 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD SEP 21 PY 2005 VL 23 IS 1 BP 89 EP 102 DI 10.1152/physiolgenomics.00068.2005 PG 14 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 967AZ UT WOS:000232065200011 PM 16046619 ER PT J AU Chodosh, J Morton, SC Mojica, W Maglione, M Suttorp, MJ Hilton, L Rhodes, S Shekelle, P AF Chodosh, J Morton, SC Mojica, W Maglione, M Suttorp, MJ Hilton, L Rhodes, S Shekelle, P TI Meta-analysis: Chronic disease self-management programs for older adults SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DEPENDENT DIABETES-MELLITUS; LIFE-STYLE MODIFICATION; BLOOD-PRESSURE; PRIMARY-CARE; CHRONIC ILLNESS; ESSENTIAL-HYPERTENSION; PATIENT EDUCATION; METABOLIC CONTROL; GLYCEMIC CONTROL AB Background: Although enthusiasm is growing for self-management programs for chronic conditions, there are conflicting data regarding their effectiveness and no agreement on their essential components. Purpose: To assess the effectiveness and essential components of self-management programs for hypertension, osteoarthritis, and diabetes mellitus. Data Sources: The authors searched multiple sources dated through September 2004, including the Cochrane Library, MEDLINE, PSycINFO, and Nursing and Allied Health databases, and bibliographies of 87 previous reviews. Study Selection: Randomized trials that compared outcomes of self-management interventions with a control or with usual care for diabetes mellitus, osteoarthritis, or hypertension; outcomes included hemoglobin A,c level, fasting blood glucose level, weight, blood pressure, pain, or function. Data Extraction: Two reviewers independently identified trials and extracted data regarding whether the intervention used tailored adjustments to meet individual patient needs, a group setting, feedback, and psychological services, and whether the intervention was provided by the patient's usual physician. Data Synthesis: Of 780 studies screened, 53 studies contributed data to the random-effects meta-analysis (26 diabetes studies, 14 osteoarthritis studies, and 13 hypertension studies). Self-management interventions led to a statistically and clinically significant pooled effect size of -0.36 (95% CI, -0.52 to -0.21) for hemoglobin A,c, equivalent to a reduction in hemoglobin A,, level of about 0.81%. Self-management interventions decreased systolic blood pressure by 5 mm Hg (effect size, -0.39 [CI, -0.51 to -0.28]) and decreased diastolic blood pressure by 4.3 mm Hg (effect size, -0.51 [CI, -0.73 to -0.30]). Pooled effects of self-management interventions were statistically significant but clinically trivial for pain and function outcomes for osteoarthritis. No consistent results supported any of the 5 characteristics examined as essential for program success. Limitations: Studies had variable quality, and possible publication bias was evident. Conclusions: Self-management programs for diabetes mellitus and hypertension probably produce clinically important benefits. The elements of the programs most responsible for benefits cannot be determined from existing data, and this inhibits specification of optimally effective or cost-effective programs. Osteoarthritis self-management programs do not appear to have clinically beneficial effects on pain or function. C1 Greater Los Angeles Vet Affairs Healthcare Syst, GRECC 11G, Los Angeles, CA 90073 USA. So Calif Evidence Based Practice Ctr, RAND Hlth Div, Santa Monica, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Chodosh, J (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, GRECC 11G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 88 TC 367 Z9 374 U1 8 U2 52 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 20 PY 2005 VL 143 IS 6 BP 427 EP 438 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 967OG UT WOS:000232099900004 PM 16172441 ER PT J AU Fang, MC Singer, DE Chang, YC Hylek, EM Henault, LE Jensvold, NG Go, AS AF Fang, MC Singer, DE Chang, YC Hylek, EM Henault, LE Jensvold, NG Go, AS TI Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation - The AnTicoagulation and risk factors in atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Article DE anticoagulants; atrial fibrillation; risk factors; stroke; women ID INTRACRANIAL HEMORRHAGE; ANTITHROMBOTIC THERAPY; PREDICTING STROKE; PARTICIPANTS; WARFARIN; HEALTH; TRIALS; DEATH; CLASSIFICATION; PREVENTION AB Background - Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation (AF). We examined data from a large contemporary cohort of AF patients to address this question. Methods and Results - We prospectively studied 13 559 adults with AF and recorded data on patients' clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke, peripheral embolism, and major hemorrhagic events through searching validated computerized databases and medical record review. We compared event rates by patient sex using multivariable log-linear regression, adjusting for clinical risk factors for stroke, and stratifying by warfarin use. We identified 394 ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin. After multivariable analysis, women had higher annual rates of thromboembolism off warfarin than did men (3.5% versus 1.8%; adjusted rate ratio [RR], 1.6; 95% CI, 1.3 to 1.9). There was no significant difference by sex in 30-day mortality after thromboembolism (23% for both). Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men (RR, 0.4; 95% CI, 0.3 to 0.5; and RR, 0.6; 95% CI, 0.5 to 0.8, respectively), with similar annual rates of major hemorrhage (1.0% and 1.1%, respectively). Conclusions - Women are at higher risk than men for AF-related thromboembolism off warfarin. Warfarin therapy appears be as effective in women, if not more so, than in men, with similar rates of major hemorrhage. Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF. C1 Univ Calif San Francisco, Hospitalist Grp, Dept Med, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Gen Internal Med & Clin Epidemiol Unit, Boston, MA 02215 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Fang, MC (reprint author), Univ Calif San Francisco, Hospitalist Grp, Dept Med, 533 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA. EM mfang@medicine.ucsf.edu FU NIA NIH HHS [K23 AG028978, AG15478, R01 AG015478] NR 31 TC 205 Z9 217 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 20 PY 2005 VL 112 IS 12 BP 1687 EP 1691 DI 10.1161/CIRCULATIONAHA.105.553438 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 965VP UT WOS:000231978800004 PM 16157766 ER PT J AU Arnlov, J Pencina, MJ Nam, BH Meigs, JB Fox, CS Levy, D D'Agostino, RB Vasan, RS AF Arnlov, J Pencina, MJ Nam, BH Meigs, JB Fox, CS Levy, D D'Agostino, RB Vasan, RS TI Relations of insulin sensitivity to longitudinal blood pressure tracking - Variations with baseline age, body mass index, and blood pressure SO CIRCULATION LA English DT Article DE blood pressure; epidemiology; hypertension; insulin; obesity ID SYMPATHETIC-NERVOUS-SYSTEM; GLUCOSE-TOLERANCE TEST; FASTING INSULIN; RESISTANCE ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; INCIDENT HYPERTENSION; NONDIABETIC SUBJECTS; PLASMA-INSULIN; RISK-FACTORS; MEN AB Background - The relations of insulin sensitivity ( IS) to hypertension incidence may vary according to baseline age, body mass index (BMI), and blood pressure ( BP). Methods and Results - We investigated the relations of IS (insulin sensitivity index, ISI0,120) to 4-year incidence of hypertension and BP progression in 1933 nonhypertensive Framingham Study participants ( median age, 51 years; 56% women). Analyses were stratified by age ( less than versus greater than or equal to median), BMI (< 25 [ normal], 25 to < 30 [overweight], >= 30 kg/m(2) [obese]), and BP category (systolic BP >= 130 or diastolic BP >= 85, "high normal" per the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP [JNC-VI] versus BP < 130/85 mm Hg). On follow-up, 41% of participants had BP progression ( >= 1 BP stage increase) and 18% had development of hypertension (systolic BP >= 140 or diastolic BP >= 90 mm Hg or antihypertensive medication use). In younger ( < 51 years) people with normal BMI and baseline BP < 130/ 85 mm Hg, the second-to-fourth ISI0,120 quartiles were associated with lower multivariable-adjusted odds for hypertension incidence (0.27; 95% CI, 0.09 to 0.83; P < 0.05) and BP progression (0.37; 95% CI, 0.18 to 0.77; P < 0.01) relative to the lowest ( most insulin resistant) quartile. IS was not related to BP progression or hypertension incidence in older individuals, in obese participants, or in people with BP >= 130/ 85 mm Hg. Conclusions - In our large community-based sample, reduced IS predicted BP tracking principally in younger people with normal BMI and BP < 130/85 mm Hg. Effect modification by age, BMI, and baseline BP may explain variation in the results of prior clinical investigations relating IS to hypertension incidence. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Cardiol Sect, Dept Med, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Uppsala Univ, Dept Publ Hlth & Caring Sci, Sect Geriatr, S-75105 Uppsala, Sweden. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Arnlov, Johan/N-9886-2013; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24 HL04334, N01-HC-25195] NR 48 TC 24 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 20 PY 2005 VL 112 IS 12 BP 1719 EP 1727 DI 10.1161/CIRCULATIONAHA.105.535039 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 965VP UT WOS:000231978800008 PM 16157770 ER PT J AU Kathiresan, S Gabriel, SB Yang, Q Lochner, AL Larson, MG Levy, D Tofler, GH Hirschhorn, JN O'Donnell, CJ AF Kathiresan, S Gabriel, SB Yang, Q Lochner, AL Larson, MG Levy, D Tofler, GH Hirschhorn, JN O'Donnell, CJ TI Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels SO CIRCULATION LA English DT Article DE plasminogen; epidemiology; genetics; genomics; fibrinolysis ID INSULIN-RESISTANCE ATHEROSCLEROSIS; ACUTE MYOCARDIAL-INFARCTION; LINKAGE DISEQUILIBRIUM; HUMAN GENOME; ASSOCIATION; DETERMINANTS; DISEASE; TESTS; RISK; IDENTIFICATION AB Background - Using a linkage disequilibrium (LD) - based approach, we sought to comprehensively define common genetic variation at the plasminogen activator inhibitor-1 ( PAI-1) locus and relate common single nucleotide polymorphisms ( SNPs) and haplotypes to plasma PAI-1 levels. Methods and Results - In reference pedigrees, we defined LD structure across a 50-kb genomic segment spanning the PAI-1 locus via a dense SNP map ( 1 SNP every 2 kb). Eighteen sequence variants that capture underlying common genetic variation were genotyped in 1328 unrelated Framingham Heart Study participants who had plasma PAI-1 antigen levels measured. Regression analyses were used to examine associations of individual SNPs and of inferred haplotypes with multivariable-adjusted PAI-1 levels. Two genetic variants, SNP rs2227631 and the 4G/5G polymorphism, were strongly associated ( P < 0.0001) with PAI-1 levels. SNP rs2227631 is in tight LD ( D' = 0.97, r(2) = 0.78) with the 4G/5G polymorphism, which makes it difficult to distinguish which of these 2 polymorphisms is responsible for the association with PAI-1 levels. In stepwise analysis considering all polymorphisms tested, 3 SNPs, rs2227631 ( or the correlated 4G/5G polymorphism), rs6465787,and rs2227674, each explained 2.5%, 1%, and 1%, respectively, of the residual variance in multivariable-adjusted PAI-1 levels ( stepwise P < 0.0001, P = 0.04, and P = 0.03, respectively). A single common haplotype, at 50% frequency among Framingham Heart Study participants, was strongly associated with higher PAI-1 levels ( haplotype-specific P = 0.00001). The susceptibility haplotype harbors the minor alleles of SNP rs2227631 and the 4G/5G polymorphism. Conclusions - Three sequence variants at the PAI-1 locus, in sum, explain approximate to 5% of the residual variance in multivariable-adjusted PAI-1 levels. For quantitative cardiovascular traits such as circulating biomarkers, defining LD structure in a candidate gene followed by association analyses with both SNPs and haplotypes is an effective approach to localize common susceptibility alleles. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Harvard Univ, Sch Med, Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014; OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [HL66582, N01-HC-25195] NR 37 TC 44 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 20 PY 2005 VL 112 IS 12 BP 1728 EP 1735 DI 10.1161/CIRCULATIONAHA.105.547836 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 965VP UT WOS:000231978800009 PM 16172282 ER PT J AU London, WB Castleberry, RP Matthay, KK Look, AT Seeger, RC Shimada, H Thorner, P Brodeur, G Maris, JM Reynolds, CP Cohn, SL AF London, WB Castleberry, RP Matthay, KK Look, AT Seeger, RC Shimada, H Thorner, P Brodeur, G Maris, JM Reynolds, CP Cohn, SL TI Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; NEURO-BLASTOMA; PROGNOSTIC FACTORS; N-MYC; GENE AMPLIFICATION; STAGE; SURVIVAL; THERAPY; CHEMOTHERAPY; ONCOGENE AB Purpose In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision. Methods To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321 p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected. Results Thirty-seven percent of patients were younger than 365 days, and 64% were ! 365 days old (4-year event-free survival [EFS] rate SE: 83% +/- 1% [n = 1,339] and 45% +/- 1 % [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were : 460 days old (4-year EFS rate +/- SE: 82% +/- 1 % [n = 1,589] and 42% +/- 1 % [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% +/- 3%; n = 135) fell into a lower risk group. Conclusion The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days. C1 Univ Florida, Dept Stat, Gainesville, FL 32601 USA. Univ Florida, Childrens Oncol Grp, Gainesville, FL 32601 USA. Univ Alabama, Childrens Hosp, Birmingham, AL USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NW Univ, Feinberg Sch Med, Chicago, IL USA. RP London, WB (reprint author), Univ Florida, Dept Stat, 104 N Main St,600, Gainesville, FL 32601 USA. EM wendy@cog.ufl.edu OI Reynolds, C. Patrick/0000-0002-2827-8536; Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [U10 CA13539, U10 CA29139, U10 CA98413-01] NR 38 TC 162 Z9 168 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2005 VL 23 IS 27 BP 6459 EP 6465 DI 10.1200/JCO.2005.05.571 PG 7 WC Oncology SC Oncology GA 969KN UT WOS:000232233100006 PM 16116153 ER PT J AU George, RE London, WB Cohn, SL Maris, JM Kretschmar, C Diller, L Brodeur, GM Castleberry, RP Look, AT AF George, RE London, WB Cohn, SL Maris, JM Kretschmar, C Diller, L Brodeur, GM Castleberry, RP Look, AT TI Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: A Pediatric Oncology Group Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HIGH-RISK NEUROBLASTOMA; IN-SITU HYBRIDIZATION; N-MYC; NEURO-BLASTOMA; GENE AMPLIFICATION; METASTATIC NEUROBLASTOMA; MULTIVARIATE-ANALYSIS; DNA PLOIDY AB Purpose To determine predictive strength of tumor cell ploidy and MYCN gene amplification on survival of children older than 12 months with disseminated neuroblastoma (NB). Patients and Methods Of 648 children with stage D NB enrolled onto the Pediatric Oncology Group NB Biology Study 9047 (1990-2000), 560 children were assessable for ploidy and MYCN amplification. Treatment of patients older than 12 months varied; most receiving high-dose chemotherapy with stem-cell rescue. Infants received standard chemotherapy, depending on MYCN status and ploidy. Results Among stage D MYCN-amplified patients, 4-year event-free survival (EFS) +/- SE had no prognostic significance for tumor cell ploidy for patients either younger than 12 months or >= 12 months old. However, among stage D nonamplified-MYCN patients, 4-year EFS for those with tumor hyperdiplody (DNA index [DI] > 1) was clearly superior to those with diploidy (DI <= 1): younger than 12 months, 83.7% +/- 4.4% (n = 87) versus 46.2% +/- 13.8% (n = 13; P = .0003); and for 12- to 24-month-old children, 72.7% +/- 10.2% (n = 22) versus 26.7% +/- 13.2% (n = 16; P = .0092). Further analysis suggested better prognoses in the 12- to 18-month-old subgroup with hyperdiploid tumors (4-year EFS, 92.9% +/- 7.2%) compared with the 19- to 24-month-old subgroup (4-year EFS, 37.5% +/- 21.0%; P = .0037). In children older than 24 months, outcome was dire (< 20% long-term survival), regardless of ploidy or MYCN status. Conclusion Children 12 to 18 months old with metastatic NB had favorable outcomes with high-dose therapy if their tumors were hyperdiploid and lacked MYCN amplification. This subgroup may respond well to contemporary chemotherapy, and could be spared intensive myeloablative therapy with stem-cell rescue. C1 Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston Floating Hosp Infants & Children, Boston, MA USA. Univ Florida, Childrens Oncol Grp, Gainesville, FL USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. Univ Alabama, Birmingham, AL USA. RP George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Dana 322,44 Binney St, Boston, MA 02115 USA. EM rani_george@dfci.harvard.edu OI Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [U10 CA30969, CA-39771, CA25408, U10 CA29139]; NINDS NIH HHS [K08NS047983] NR 29 TC 77 Z9 81 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2005 VL 23 IS 27 BP 6466 EP 6473 DI 10.1200/JCO.2005.05.582 PG 8 WC Oncology SC Oncology GA 969KN UT WOS:000232233100007 PM 16116152 ER PT J AU Emmons, KM Puleo, E Park, E Gritz, ER Butterfield, RM Weeks, JC Mertens, A Li, FP AF Emmons, KM Puleo, E Park, E Gritz, ER Butterfield, RM Weeks, JC Mertens, A Li, FP TI Peer-delivered smoking counseling for Childhood Cancer Survivors increases rate of cessation: The Partnership for Health Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-Behavioral-Medicine CY MAR 19-22, 2003 CL Salt Lake City, UT SP Soc Behav Med ID SELF-HELP MATERIALS; COST-EFFECTIVENESS; RANDOMIZED TRIAL; TOBACCO USE; INTERVENTION; COHORT; PARTICIPANTS; PREDICTORS; DEPENDENCE; BEHAVIORS AB Purpose Cancer survivors smoke at rates that are only slightly lower than the general population. This article reports on the final outcomes of Partnership for Health, a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study (CCSS). Methods This study is a randomized control trial with follow-up at 8 and 12 months that involved smokers (n = 796) enrolled onto the CCSS cohort. Participants were randomly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor, tailored and targeted materials, and free nicotine replacement therapy. The intervention was delivered by telephone and postal service mail. Results The quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month (16.8% v 8.5%; P < .01) and 12-month follow-ups (15% v 9%; P <= .01). Controlling for baseline self-efficacy and readiness to change, the intervention group was twice as likely to quit smoking, compared with the self-help group. Smoking cessation rate increased with an increase in the number of counseling calls. The cost of delivering the intervention was approximately $300 per participant. The incremental cost-effectiveness of the intervention compared with controls was $5,371 per additional quit. Conclusion Interventions to prevent future illnesses are of critical importance to childhood cancer survivors. The Partnership for Health intervention resulted in a doubling of smoking cessation quit rates. Because of the seriousness of smoking among childhood cancer survivors, this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Univ Massachusetts, Amherst, MA 01003 USA. Univ Minnesota, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Karen_M_Emmons@dfci.harvard.edu FU NCI NIH HHS [U24-CA55727, R01-CA77780] NR 42 TC 78 Z9 78 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2005 VL 23 IS 27 BP 6516 EP 6523 DI 10.1200/JCO.2005.07.048 PG 8 WC Oncology SC Oncology GA 969KN UT WOS:000232233100013 PM 16116148 ER PT J AU Stewart, AJ Scher, HI Chen, MH McLeod, DG Carroll, PR Moul, JW D'Amico, AV AF Stewart, AJ Scher, HI Chen, MH McLeod, DG Carroll, PR Moul, JW D'Amico, AV TI Prostate-specific antigen nadir and cancer-specific mortality following hormonal therapy for prostate-specific antigen failure SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; NATURAL-HISTORY; MITOXANTRONE; PREDNISONE; DOCETAXEL; DATABASE AB Purpose For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA), we evaluated whether a PSA nadir of more than 0.2 ng/mL was significantly associated with prostate cancer-specific mortality (PCSM). Patients and Methods The study cohort comprised 747 men with rising PSA and negative bone scan after surgery (n = 486) or radiation therapy (n = 261) who were treated with AST. Cox regression was used to evaluate whether a significant association existed between the PSA nadir level after 8 months of AST and the time to PCSM, controlling for treatment and known prognostic factors. Results The post-AST PSA nadir (p(Cox) < .0001), the pre-AST PSA doubling time (DT) (p(Cox) = .002), PSA level (P = .0001), and Gleason eight to 10 cancers (p(Cox) = .01) were significantly associated with time to PCSM. The adjusted hazard ratio for PCSM was 20 (95% Cl, 7 to 61; P-Cox < .0001), for men with a PSA nadir of more than 0.2 ng/mL as compared with all others. A PSA DT of less than 3 months was observed in 30% (224 of 747) of the study cohort. Of the 28 observed prostate cancer deaths, 21 (75%) occurred in men whose PSA nadir was more than 0.2 ng/mL and who had a PSA DT of less than 3 months. Conclusion A PSA nadir of more than 0.2 ng/mL after 8 months of AST given for postoperative or postradiation PSA failure is significantly associated with PCSM and is clinically significant because it accounted for 75% of the cancer deaths observed in this study. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Connecticut, Storrs, CT USA. Walter Reed Hosp, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Durham, NC USA. RP Stewart, AJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM ajsintheus@yahoo.co.uk FU NCI NIH HHS [R25 CA089017] NR 17 TC 66 Z9 67 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2005 VL 23 IS 27 BP 6556 EP 6560 DI 10.1200/JCO.2005.20.966 PG 5 WC Oncology SC Oncology GA 969KN UT WOS:000232233100018 PM 16170163 ER PT J AU Ayanian, JZ Zaslavsky, AM Guadagnoli, E Fuchs, CS Yost, KJ Creech, CM Cress, RD O'Connor, LC West, DW Wright, WE AF Ayanian, JZ Zaslavsky, AM Guadagnoli, E Fuchs, CS Yost, KJ Creech, CM Cress, RD O'Connor, LC West, DW Wright, WE TI Patients' perceptions of quality of care for colorectal cancer by race, ethnicity, and language SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTH-CARE; HOSPITAL-CARE; PERFORMANCE; RATINGS; SATISFACTION; OUTCOMES; THERAPY AB Purpose To identify opportunities for improving care, we evaluated patients' perceptions of the quality of their cancer care by race, ethnicity, and language. Patients and Methods We surveyed a population-based cohort of 1,067 patients with colorectal cancer in northern California approximately 9 months after diagnosis. Adjusting for clinical and demographic factors, mean problem scores were analyzed on a 100-point scale for six domains of care. Results Mean problem scores were highest for health information (47.8), followed by treatment information (32.3), psychosocial care (31.7), coordination of care (21.3), confidence in providers (13.1), and access to cancer care (12.7). In adjusted comparisons with white patients, African American patients reported more problems with coordination of care (difference, 9.8; P < .001), psychosocial care (difference, 7.2; P = .03), access to care (difference, 6.6; P = .03), and health information (difference, 12.5; P < .001). Asian/Pacific Islander patients reported more problems than did white patients with coordination of care (difference, 13.2; P < .001), access to care (difference, 15.5; P < .001), and health information (difference, 12.6; P = .004). Hispanic patients tended to report more problems with coordination of care (difference, 4.4; P = .06), access to care (difference, 5.8; P = .08), and treatment information (difference, 7.0; P = .06). Non-English-speaking white patients reported more problems than other white patients with coordination of care (difference, 21.9; P < .001), psychosocial care (difference, 16.1; P = .009), access to care (difference, 19.8; P = .003), and treatment information (difference, 17.8; P = .002). Non-English-speaking Hispanic patients reported more problems than other Hispanic patients with confidence in providers (difference, 16.9; P = .01). Conclusion Efforts to improve patients' experiences with cancer care should address disparities by race, ethnicity, and language, particularly in coordination of care, access to care, and the provision of relevant information. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med & Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Evanston NW Healthcare Res Inst, Ctr Outcomes Res & Educ, Evanston, IL USA. Canc Surveillance Program, Sacramento, CA USA. Inst Publ Hlth, Berkeley, CA USA. No Calif Canc Ctr, Union City, CA USA. Calif State Univ Sacramento, Canc Surveillance Sect, Dept Hlth Sci, Sacramento, CA 95819 USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM ayanian@hcp.med.harvard.edu FU AHRQ HHS [R01 HS09869]; NCI NIH HHS [U01 CA93324] NR 32 TC 108 Z9 108 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2005 VL 23 IS 27 BP 6576 EP 6586 DI 10.1200/JCO.2005.06.102 PG 11 WC Oncology SC Oncology GA 969KN UT WOS:000232233100021 PM 16116149 ER PT J AU Cloughesy, TF Kuhn, J Robins, HI Abrey, L Wen, P Fink, K Lieberman, FS Mehta, M Chang, S Yung, A DeAngelis, L Schiff, D Junck, L Groves, M Paquette, S Wright, J Lamborn, K Sebti, SM Prados, M AF Cloughesy, TF Kuhn, J Robins, HI Abrey, L Wen, P Fink, K Lieberman, FS Mehta, M Chang, S Yung, A DeAngelis, L Schiff, D Junck, L Groves, M Paquette, S Wright, J Lamborn, K Sebti, SM Prados, M TI Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: A North American brain tumor consortium study 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 TRANSFERASE INHIBITOR R115777; FARNESYLTRANSFERASE INHIBITORS; GLIOBLASTOMA-MULTIFORME; GUANOSINE TRIPHOSPHATE; THERAPEUTIC STRATEGY; ADVANCED CANCER; RAS; GROWTH; METABOLISM; PACLITAXEL AB Purpose: To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antielpileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. Patients and Methods: Recurrent malignant glioma patients were treated with tipifarnilb using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. Results: Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration-time curve (AUC)(0-12 hours) was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). Conclusion: Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12 hours), and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients. C1 Univ Calif Los Angeles, Henry E Singleton Brain Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Wisconsin, Madison, WI USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Univ S Florida, Drug Discovery Program, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. RP Cloughesy, TF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Neurooncol Program, 710 Westwood Plaza,Reed Bldg,Room 1-230, Los Angeles, CA 90095 USA. EM tcloughe@ucla.edu OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [U01CA62407-08, 5-U01CA62399-09, CA16672, CA62412, CA62426, CA62455-08, CA76292, U01CA62399, U01CA62405, U01CA62421-08, U01CA62422]; NCRR NIH HHS [M01 RR03186, M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR0865] NR 50 TC 37 Z9 38 U1 0 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 SEP 20 PY 2005 VL 23 IS 27 BP 6647 EP 6656 DI 10.1200/JCO.2005.10.068 PG 10 WC Oncology SC Oncology GA 969KN UT WOS:000232233100029 PM 16170172 ER PT J AU Livestro, DP Muzikansky, A Kaine, EM Flotte, TJ Sober, AJ Mihm, MC Michaelson, JS Cosimi, AB Tanabe, KK AF Livestro, DP Muzikansky, A Kaine, EM Flotte, TJ Sober, AJ Mihm, MC Michaelson, JS Cosimi, AB Tanabe, KK TI Biology of desmoplastic melanoma: A case-control comparison with other melanomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYMPH-NODE BIOPSY; MALIGNANT-MELANOMA; NEUROTROPIC MELANOMA; PROGNOSTIC-FACTORS; PATTERNS; RECURRENCE AB Purpose: Previous studies have established that patients with desmoplastic melanoma (DM) have thicker primary tumors. Consequently, comparisons with other forms of melanoma have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing DM with other forms of melanoma. Patients and Methods: From a database of 3,202 melanoma patients treated at one institution, 89 patients with DM and 178 case-matched control patients (2:1) were identified by matching for tumor thickness, age, sex, and year of diagnosis. Clinical, pathologic, and outcome information was obtained from chart review. Results: Controls were matched successfully to patients for tumor thickness, age, sex, and year of diagnosis. Presentation with American Joint Committee on Cancer stage III or IV disease is less common in patients with DM compared to case-matched control patients (5% v 21%; P < .001). Re-excisions to obtain clear surgical margins are required more often in patients with DIM compared to case-matched control patients (21% v 6%; P < .001). Risk of positive sentinel nodes is lower in patients with DM compared to case-matched control patients (8% v 34%; P = .013). Despite these differences, survival rates of patients with DM are the same as case-matched control patients. Conclusion: Use of case-matched control patients matched for tumor thickness avoids biases introduced by the advanced Breslow stage of DMs. DMs are more locally aggressive than thickness-matched controls, and positive sentinel nodes are limited to patients with thick primary tumors. Importantly, patients with DM have survival rates similar to patients with other melanomas of similar thickness. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Utrecht, Med Ctr, Fac Med, Utrecht, Netherlands. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Cox Bldg,Rm 626,100 Blossom St, Boston, MA 02114 USA. EM ktanabe@partners.org NR 26 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2005 VL 23 IS 27 BP 6739 EP 6746 DI 10.1200/JCO.2005.04.515 PG 8 WC Oncology SC Oncology GA 969KN UT WOS:000232233100039 PM 16170181 ER PT J AU Mankin, HJ Hornicek, FJ Ortiz-Cruz, E Villafuerte, J Gebhardt, MC AF Mankin, HJ Hornicek, FJ Ortiz-Cruz, E Villafuerte, J Gebhardt, MC TI Aneurysmal bone cyst: A review of 150 patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID MALIGNANT TRANSFORMATION; CHILDREN; SECONDARY; INJECTION; LESIONS AB Purpose: We have reviewed a series of 150 aneurysmal bone cysts treated over the last 20 years. Patients and Methods: The lesions were principally located in the tibia, femur, pelvis, humerus, and spine and, in most cases, presented the imaging appearance originally described by Jaffe and Lichtenstein as a blowout with thin cortices. Results: Only one of the patients was believed to have an osteoblastoma of the spine with secondary development of an aneurysmal bone cyst, and none of the patients developed additional lesions. The patients were treated primarily with curettage and implantation of allograft chips or polymethylmethacrylate, but some patients were treated with insertion of autografts or allografts. The local recurrence rate was 20%, which is consistent with that reported by other centers. Conclusion: Aneurysmal bone cysts are enigmatic lesions of unknown cause and presentation and are difficult to distinguish from other lesions. Overall, the treatment is satisfactory, but it is possible that newer approaches, such as improved magnetic resonance imaging studies, may help diagnose the lesions and allow the physicians to plan for more effective treatment protocols. C1 Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA 02114 USA. EM hmankin@partners.org OI ORTIZ CRUZ, EDUARDO J./0000-0002-1405-0688 NR 45 TC 116 Z9 123 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2005 VL 23 IS 27 BP 6756 EP 6762 DI 10.1200/JCO.2005.15.255 PG 7 WC Oncology SC Oncology GA 969KN UT WOS:000232233100041 PM 16170183 ER PT J AU Massie, BM AF Massie, BM TI Aspirin use in chronic heart failure - What should we recommend to the practitioner? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONVERTING-ENZYME-INHIBITORS; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; RANDOMIZED TRIALS; ELDERLY-PATIENTS; DEATH; PREVENTION; ENALAPRIL; SURVIVAL; DISEASE AB There has been ongoing controversy as to whether aspirin should be used in patients with chronic heart failure (CHF). The argument for aspirin is that many patients have underlying coronary disease, and aspirin prevents reinfarction and other vascular events. Arguments against the routine use of aspirin are that many CHF patients do not have underlying coronary disease, and that the benefit of aspirin lessens after the first 6 to 12 months after infarction. Also, several analyses suggest that aspirin may actually worsen outcomes in CkF patients, possibly because it inhibits prostaglandins, with resulting adverse hemodynamic and renal effects. Two recent prospective randomized studies have found that aspirin is associated with more frequent hospitalizations for worsening heart failure, although it did not have an adverse effect on vascular events. These results suggest that aspirin should not be routinely used in CHF patients and be avoided in those with refractory CHF, but that it may be beneficial in patients with recent infarction or multiple vascular risk factors. C1 San Francisco VAMC, Div Cardiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Massie, BM (reprint author), San Francisco VAMC, Div Cardiol, 111C,4150 Clement St, San Francisco, CA 94121 USA. EM barry.massie@med.va.gov NR 28 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 SEP 20 PY 2005 VL 46 IS 6 BP 963 EP 966 DI 10.1016/j.jacc.2004.10.082 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 966AI UT WOS:000231991600003 PM 16168276 ER PT J AU Butler, J AF Butler, J TI More risk factors affecting heart failure outcomes! Time for hope or despair? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; METOPROLOL; CARVEDILOL; THERAPY C1 Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Butler, J (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 383 PRB,21st Ave, Nashville, TN 37232 USA. EM javed.butler@vanderbilt.edu NR 12 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 SEP 20 PY 2005 VL 46 IS 6 BP 1027 EP 1028 DI 10.1016/j.jacc.2005.06.015 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 966AI UT WOS:000231991600013 PM 16168286 ER PT J AU Sheppard, R Bedi, M Kubota, T Semigran, MJ Dec, W Holubkov, R Feldman, AM Rosenblum, WD McTiernan, CF McNamara, DM AF Sheppard, R Bedi, M Kubota, T Semigran, MJ Dec, W Holubkov, R Feldman, AM Rosenblum, WD McTiernan, CF McNamara, DM CA IMAC Invest TI Myocardial expression of Fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; INTRAVENOUS IMMUNE GLOBULIN; FAILING HUMAN HEART; SOLUBLE FAS; DILATED CARDIOMYOPATHY; PLASMA-LEVELS; APOPTOSIS; LIGAND; TESTOSTERONE; AUTOIMMUNE AB OBJECTIVES This study aimed to evaluate the role of gene expression for predicting myocardial recovery in recent-onset cardiomyopathy. BACKGROUND Apoptosis may limit ventricular recovery. We examined the myocardial expression of Fas, Fas ligand (FasL), tumor necrosis factor (TNF)-alpha, and TNF receptor 1 (TNFR1), and myocardial recovery in patients from the multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC) study. METHODS Endomyocardial biopsy samples were obtained in 20 patients with recent-onset (< 6 months) idiopathic dilated cardiomyopathy (left ventricular ejection fraction [LVEF] <= 0.40). The LVEF was assessed at baseline and at 6 and 12 months by nuclear scans. Myocardial expression was assessed by ribonuclease (RNase) protection, normalized to a constitutively active gene (glyceraldehydes 3-phosphate dehydrogenase [GAPDH]) and reported as percent GAPDH expression. The change in LVEF at 6 and 12 months was compared by tertiles of expression. RESULTS For all patients (14 men, 6 women; age 46.5 +/- 10.7 years), the mean LVEF was 0.28 +/- 0.05 at baseline and 0.40 +/- 0.14 at six months. Patients in the highest tertile of Fas expression had minimal improvement at six months (AEF = 0.03 +/- 0.05) when compared with the intermediate (Delta EF = 0.10 +/- 0.13) and lowest tertiles (Delta EF = 0.21 +/- 0.11, change in LVEF by tertile, p = 0.006). A similar relationship was seen with TNFR1 expression (highest tertile, Delta EF 0.06 +/- 0.07; lowest tertile, Delta EF = 0.21 +/- 0.11, p = 0.02). In contrast with Fas and TNFR1, expression of TNF-alpha and FasL did not predict recovery of LV function. CONCLUSIONS In cardiomyopathy of recent onset, increased expression of Fas and TNFR1 was associated with minimal recovery of LV function. Apoptosis limits myocardial recovery, and represents a potential target for therapeutic intervention. C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Heart Failure Transplantat Program, Pittsburgh, PA 15213 USA. McGill Univ, Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3A 2T5, Canada. Kyushu Univ, Fukuoka 812, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. New York Med Coll, Valhalla, NY 10595 USA. RP McNamara, DM (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Heart Failure Transplantat Program, 566 Scaife Hall,200 Lothrop St, Pittsburgh, PA 15213 USA. EM mcnamaradm@upmc.edu FU NHLBI NIH HHS [K24 HL69912, R01 HL75038] NR 23 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 20 PY 2005 VL 46 IS 6 BP 1036 EP 1042 DI 10.1016/j.jacc.2005.05.067 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 966AI UT WOS:000231991600015 PM 16168288 ER PT J AU Andersen, OM Reiche, J Schmidt, V Gotthardt, M Spoelgen, R Behlke, J von Arnim, CAF Breiderhoff, T Jansen, P Wu, X Bales, KR Cappai, R Masters, CL Gliemann, J Mufson, EJ Hyman, BT Paul, SM Nykjaer, A Willnow, TE AF Andersen, OM Reiche, J Schmidt, V Gotthardt, M Spoelgen, R Behlke, J von Arnim, CAF Breiderhoff, T Jansen, P Wu, X Bales, KR Cappai, R Masters, CL Gliemann, J Mufson, EJ Hyman, BT Paul, SM Nykjaer, A Willnow, TE TI Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE endocytic receptors; knockout mouse; neurodegeneration; Vps10p-domain receptors ID APOLIPOPROTEIN-E RECEPTOR; CYTOPLASMIC DOMAIN; ALZHEIMER-DISEASE; BETA; BINDING; TRANSPORT; TRAFFICKING; CLEAVAGE; FRAGMENT; PEPTIDE AB sorLA (sorting protein-related receptor) is a type-1 membrane protein of unknown function that is expressed in neurons. Its homology to sorting receptors that shuttle between the plasma membrane, endosomes, and the Golgi suggests a related function in neuronal trafficking processes. Because expression of sorLA is reduced in the brain of patients with Alzheimer's disease (AD), we tested involvement of this receptor in intracellular transport and processing of the amyloid precursor protein (APP) to the amyloid) beta-peptide (A beta), the principal component of senile plaques. We demonstrate that sorLA interacts with APP in vitro and in living cells and that both proteins colocalize in endosomal and Golgi compartments. Overexpression of sorLA in neurons causes redistribution of APP to the Golgi and decreased processing to A beta, whereas ablation of sorLA expression in knockout mice results in increased levels of A beta in the brain similar to the situation in AD patients. Thus, sorLA acts as a sorting receptor that protects APP from processing into A beta and thereby reduces the burden of amyloidogenic peptide formation. Consequently, reduced receptor expression in the human brain may increase A beta production and plaque formation and promote spontaneous AD. C1 Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Aarhus Univ, Inst Med Biochem, DK-8000 Aarhus, Denmark. Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. RP Willnow, TE (reprint author), Max Delbruck Ctr Mol Med, Robert Roessle Str 10, D-13125 Berlin, Germany. EM willnow@mdc-berlin.de RI Cappai, Roberto/B-3347-2010; OI Cappai, Roberto/0000-0002-9505-8496; Nykjaer, Anders/0000-0001-6422-6736; Gotthardt, Michael/0000-0003-1788-3172 NR 25 TC 325 Z9 341 U1 1 U2 21 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 20 PY 2005 VL 102 IS 38 BP 13461 EP 13466 DI 10.1073/pnas.0503689102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 967TW UT WOS:000232115100021 PM 16174740 ER PT J AU Finberg, KE Wagner, CA Bailey, MA Paunescu, TG Breton, S Brown, D Giebisch, G Geibel, JP Lifton, RP AF Finberg, KE Wagner, CA Bailey, MA Paunescu, TG Breton, S Brown, D Giebisch, G Geibel, JP Lifton, RP TI The B1-subunit of the H+ ATPase is required for maximal urinary acidification SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE collecting duct; intercalated cell; pH homeostasis; renal tubular acidosis; vacuolar H+ ATPase ID RENAL TUBULAR-ACIDOSIS; BASE-BALANCE; B1 SUBUNIT; KIDNEY; EXPRESSION; MUTATIONS; ISOFORM; CELLS; ALDOSTERONE; (H+)-ATPASE AB The multisubunit vacuolar-type H(+)ATPases mediate acidification of various intracellular organelles and in some tissues mediate H+ secretion across the plasma membrane. Mutations in the B1-subunit of the apical H(+)ATPase that secretes protons in the distal nephron cause distal renal tubular acidosis in humans, a condition characterized by metabolic acidosis with an inappropriately alkaline urine. To examine the detailed cellular and organismal physiology resulting from this mutation, we have genera ted mice deficient in the B1-subunit (Atp6v1b1(-/-) mice). Urine pH is more alkaline and metabolic acidosis is more severe in Atp6v1b1(-/-) mice after oral acid challenge, demonstrating a failure of normal urinary acidification. In Atp6v1b1(-/-) mice, the normal urinary acidification induced by a lumen-negative potential in response to furosemide infusion is abolished. After an acute intracellular acidification, Na+-independent pH recovery rates of individual Atp6v1b1(-/-) intercalated cells of the cortical collecting duct are markedly reduced and show no further decrease after treatment with the selective H(+)ATPase inhibitor concanamycin. Apical expression of the alternative B-subunit isoform, B2, is increased in Atp6v1b1(-/-) medulla and colocalizes with the H(+)ATPase E-subunit; however, the greater severity of metabolic acidosis in Atp6v1b1(-/-) mice after oral acid challenge indicates that the B2-subunit cannot fully functionally compensate for the loss of B1. Our results indicate that the B1 isoform is the major B-subunit isoform that incorporates into functional, plasma membrane H(+)ATPases in intercalated cells of the cortical collecting duct and is required for maximal urinary acidification. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Zurich, Inst Physiol, Zurich, Switzerland. Univ Edinburgh, Edinburgh, Midlothian, Scotland. RP Lifton, RP (reprint author), Yale Univ, Sch Med, 1 Gilbert St,TAC S341, New Haven, CT 06520 USA. EM richard.lifton@yale.edu FU Wellcome Trust NR 27 TC 78 Z9 80 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 20 PY 2005 VL 102 IS 38 BP 13616 EP 13621 DI 10.1073/pnas.0506769102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 967TW UT WOS:000232115100048 PM 16174750 ER PT J AU Bayram, M De Luca, L Massie, MB Gheorghiade, M AF Bayram, M De Luca, L Massie, MB Gheorghiade, M TI Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL OXYGEN-CONSUMPTION; RANDOMIZED CONTROLLED TRIAL; NATIONAL REGISTRY ADHERE; BETA-BLOCKER THERAPY; DILATED CARDIOMYOPATHY; HIBERNATING MYOCARDIUM; INTRAVENOUS MILRINONE; HOSPITALIZED-PATIENTS; INOTROPIC THERAPY; DOUBLE-BLIND AB The appropriate role of intravenous inodilator therapy (inotropic agents with vasodilator properties) in the management of acute heart failure syndromes (AHFS) has long been a subject of controversy, mainly because of the lack of prospective, placebo-controlled trials and a lack of alternative therapies. The use of intravenous inodilator,infusions, however, remains common, but highly variable. As new options emerge for the treatment of AHFS, the available information should be reviewed to determine which approaches are supported by evidence, which are used empirically without evidence, and which should be considered inappropriate. For these purposes, we reviewed data available from randomized controlled trials on short-term, intermittent, and long-term use of intravenous inodilator agents (dobutamine, dopamine, and milrinone) in AHFS. Randomized controlled trials failed to show benefits with current medications and suggested that acute, intermittent, or continuous use of inodilator infusions may increase morbidity and mortality in patients with AHFS. Their use should be restricted to patients who are hypotensive as a result of low cardiac output despite a high left ventricular filling pressure. (c) 2005 Elsevier Inc. C1 Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. Univ Michigan, Dept Med, Residency Training Program, Ann Arbor, MI 48109 USA. Univ Roma La Sapienza, Dept Cardiovasc & Resp Sci, Rome, Italy. San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. Univ San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Bayram, M (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, Galter 10-240,201 E Huron St, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu NR 79 TC 65 Z9 76 U1 0 U2 1 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 SEP 19 PY 2005 VL 96 IS 6A SU S BP 47G EP 58G DI 10.1016/j.amjcard.2005.07.021 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 969BR UT WOS:000232208900008 PM 16181823 ER PT J AU Teerlink, JR AF Teerlink, JR TI Overview of randomized clinical trials in acute heart failure syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; WORSENING RENAL-FUNCTION; SOCIETY-OF-CARDIOLOGY; DOUBLE-BLIND; RECEPTOR ANTAGONIST; NATRIURETIC PEPTIDE; INTRAVENOUS LEVOSIMENDAN; PULMONARY-EDEMA; BG9719 CVT-124 AB Acute heart failure syndromes (AHFS) are among the most frequent causes of hospitalizations in the United States. and Europe. Despite current therapies, patients with AHFS have high readmission and mortality rates. The randomized, controlled clinical trial is the standard by which contemporary therapies are evaluated, yet this tool of clinical science only recently has been rigorously applied to the development of novel therapies for patients with AHFS. This review briefly discusses some of the challenges presented in designing a clinical trial of therapies for AHFS and to describe some of the recent trials with respect to these issues in established drugs (such as milrinone, dobutamine, nitroglycerin, nitroprusside, and nesiritide) that have been approved by the US Food and Drug Administration (FDA). Recent trials of current investigational agents, such as levosimendan (the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy Versus Placebo in the Short-Term Treatment of Decompensated Heart Failure [REVIVE], the Calcium Sensitizer or Inotrope or None in Low-Output Heart Failure [CASINO] study, and the Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support [SURVIVE] trial), tezosentan (the Randomized Intravenous Tezosentan [RITZ] study and the Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Studies [VERITAS]), and tolvaptan (the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure [ACTIV-CHF] study), are also discussed. (c) 2005 Elsevier Inc. C1 San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Teerlink, JR (reprint author), San Francisco Vet Affairs Med Ctr, Cardiol Sect, 111C,4150 Clement St, San Francisco, CA 94121 USA. EM johnt@itsa.ucsf.edu RI Teerlink, John/D-2986-2012 NR 55 TC 23 Z9 23 U1 0 U2 3 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 SEP 19 PY 2005 VL 96 IS 6A SU S BP 59G EP 67G DI 10.1016/j.amjcard.2005.07.022 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 969BR UT WOS:000232208900009 PM 16181824 ER PT J AU Gheorghiade, M Teerlink, JR Mebazaa, A AF Gheorghiade, M Teerlink, JR Mebazaa, A TI Pharmacology of new agents for acute heart failure syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC TROPONIN-C; CALCIUM-SENSITIZING DRUG; GUINEA-PIG HEART; ENDOTHELIN RECEPTOR ANTAGONIST; PLASMA ARGININE VASOPRESSIN; FAILING HUMAN MYOCARDIUM; K-ATP CHANNELS; LEVOSIMENDAN IMPROVES; CONTINUOUS-INFUSION; HEALTHY-VOLUNTEERS AB Current therapies for acute heart failure syndromes (AHFS) target hemodynamics by decreasing congestion or increasing myocardial contraction. Several new agents for AHFS use novel mechanisms of action that focus on new treatment targets, such as those providing anti-ischemic and antistunning effects, blocking vasopressin receptors, or blocking endothelin-1 receptors. For example, levosimendan acts as a calcium, sensitizer and adenosine triphosphate-dependent potassium (K-ATP) channel opener that increases contraction, causes vasodilation, and provides cardioprotective effects. This is accomplished by its dual mechanism of action. Levosimendan binds to cardiac troponin C, thereby enhancing calcium myofilament responsiveness and increasing myocardial contraction without increasing intracellular calcium levels. Thus, contraction is increased with no significant increase in myocardial oxygen consumption. The opening of K-ATP channels by levosimendan causes vasodilation and exerts anti-ischemic and antistunning effects on the myocardium. Other new agents target neurohormonal pathways. Tezosentan is an antagonist of endothelin-1 receptors A and B. By inhibiting endothelin-1 receptors, tezosentan may counteract the activities of endothelin-1, which include vasoconstriction, proarrhythmic activities, potentiation of other neurohormones, and mediation of increased vascular permeability. Tolvaptan is a vasopressin V-2-receptor antagonist that functions as an aquaretic (ie, it increases urine volume and serum sodium with little or no sodium loss). Therefore, by using novel mechanisms of action, these agents may provide new opportunities for helping patients with AHFS. (c) 2005 Elsevier Inc. C1 Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Hop Lariboisiere, Dept Anesthesiol & Crit Care Med, F-75475 Paris, France. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, Galter 10-240,201 E Huron St, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Teerlink, John/D-2986-2012 NR 84 TC 23 Z9 31 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 SEP 19 PY 2005 VL 96 IS 6A SU S BP 68G EP 73G DI 10.1016/j.amjcard.2005.07.023 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 969BR UT WOS:000232208900010 PM 16181825 ER PT J AU Jiang, WY Anderson, MS Bronson, R Mathis, D Benoist, C AF Jiang, WY Anderson, MS Bronson, R Mathis, D Benoist, C TI Modifier loci condition autoimmunity provoked by Aire deficiency SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CANDIDIASIS-ECTODERMAL DYSTROPHY; POLYGLANDULAR SYNDROME TYPE-1; NONOBESE DIABETIC MICE; T-CELLS; NOD MICE; CENTRAL TOLERANCE; NEGATIVE SELECTION; DISEASE; SUSCEPTIBILITY; MHC AB Loss of function mutations in the autoimmune regulator (Aire) gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients and mutant mice lead to autoimmune manifestations that segregate as a monogenic trait, but with wide variation in the spectrum of organs targeted. To investigate the cause of this variability, the Aire knockout mutation was backcrossed to mice of diverse genetic backgrounds. The background loci strongly influenced the pattern of organs that were targeted (stomach, eye, pancreas, liver, ovary, thyroid, and salivary gland) and the severity of the targeting (particularly strong on the nonobese diabetic background, but very mild on the C57BL/6 background). Autoantibodies mimicked the disease pattern, with oligoclonal reactivity to a few antigens that varied between Aire- deficient strains. Congenic analysis and a whole genome scan showed that autoimmunity to each organ had a distinctive pattern of genetic control and identified several regions that controlled the pattern of targeting, including the major histocompatibility complex and regions of Chr1 and Chr3 previously identified in controlling type 1 diabetes. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Benoist, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, Boston, MA 02215 USA. EM dm@joslin.harvard.edu; cb@joslin.harvard.edu NR 46 TC 126 Z9 129 U1 0 U2 5 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 SEP 19 PY 2005 VL 202 IS 6 BP 805 EP 815 DI 10.1084/jcm.20050693 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 968MI UT WOS:000232166200009 PM 16172259 ER PT J AU Sweadner, KJ AF Sweadner, KJ TI Phospholemman - A new force in cardiac contractility SO CIRCULATION RESEARCH LA English DT Editorial Material DE digitalis; phospholemman; heart failure; Na,K-ATPase ID NA/K PUMP FUNCTION; NA,K-ATPASE; PHOSPHORYLATION; EXCHANGER; ATPASE; HEART C1 Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. EM sweadner@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL036271] NR 10 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 16 PY 2005 VL 97 IS 6 BP 510 EP 511 DI 10.1161/01.RES.0000184616.84960.7a PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 964QV UT WOS:000231896500002 PM 16166561 ER PT J AU Gesty-Palmer, D El Shewy, H Kohout, TA Luttrell, LM AF Gesty-Palmer, D El Shewy, H Kohout, TA Luttrell, LM TI beta-arrestin 2 expression determines the transcriptional response to lysophosphatidic acid stimulation in murine embryo fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; SIGNAL-REGULATED KINASE-1; BETA-ARRESTIN; ANGIOTENSIN-II; EGF RECEPTOR; ERK ACTIVATION; MAP KINASE; PATHWAYS; TRANSACTIVATION; ENDOCYTOSIS AB G protein-coupled receptors often employ novel signaling mechanisms, such as transactivation of epidermal growth factor (EGF) receptors or G protein-independent signals transmitted by beta-arrestins, to control the activity of extracellular signal-regulated kinases 1 and 2 (ERK1/2). In this study we investigated the role of beta-arrestins in lysophosphatidic acid (LPA) receptor-stimulated ERK1/ 2 activation using fibroblast lines derived from wild type, beta-arrestin 1, beta-arrestin 2, and beta-arrestin 1/2 knock-out mice. LPA stimulation produced robust ERK1/ 2 phosphorylation in all four backgrounds. In cells lacking beta-arrestin 2, > 80% of LPA-stimulated ERK1/ 2 phosphorylation was mediated by transactivated EGF receptors. In contrast, ERK1/ 2 activation in cells expressing beta-arrestin 2 was predominantly EGF receptor-independent. Introducing FLAG epitope-tagged beta-arrestin 2 into the beta-arrestin 1/2 null background restored EGF receptor-independent ERK1/ 2 activation, indicating that beta-arrestin 2 expression confers ERK1/ 2 activation via a distinct mechanism. To determine the contributions of beta-arrestin 2, transactivated EGF receptors, and ERK1/ 2 to LPA-stimulated transcriptional responses, we employed gene expression arrays containing cDNA markers for G protein-coupled receptor-mediated signaling. In the beta-arrestin 1/2 null background, 1 h of exposure to LPA significantly increased transcription of seven marker genes. Six of these responses were EGF receptor-dependent, and two required ERK1/ 2 activation. In beta-arrestin 2 expressing cells, three of the seven LPA-stimulated transcriptional responses observed in the beta-arrestin 1/2 null background were lost. The four residual responses were independent of EGF receptor transactivation, but all were ERK1/2-dependent. These data indicate that beta-arrestin 2 functions both to attenuate EGF receptor transactivation-dependent signaling and to promote a distinct subset of ERK1/2-mediated responses to LPA receptor activation. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Durham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. Neurocrine Biosci Inc, Dept Exploratory Discovery, San Diego, CA 92121 USA. Neurocrine Biosci Inc, Dept Mol Biol, San Diego, CA 92121 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,816 CSB,POB 250624, Charleston, SC 29425 USA. EM luttrell@musc.edu FU NIDDK NIH HHS [DK55524, DK64353] NR 43 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 16 PY 2005 VL 280 IS 37 BP 32157 EP 32167 DI 10.1074/jbc.M50746200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 963HM UT WOS:000231794800016 PM 16027114 ER PT J AU Kurosu, H Yamamoto, M Clark, JD Pastor, JV Nandi, A Gurnani, P McGuinness, OP Chikuda, H Yamaguchi, M Kawaguchi, H Shimomura, I Takayama, Y Herz, J Kahn, CR Rosenblatt, KP Kuro-o, M AF Kurosu, H Yamamoto, M Clark, JD Pastor, JV Nandi, A Gurnani, P McGuinness, OP Chikuda, H Yamaguchi, M Kawaguchi, H Shimomura, I Takayama, Y Herz, J Kahn, CR Rosenblatt, KP Kuro-o, M TI Suppression of aging in mice by the hormone Klotho SO SCIENCE LA English DT Article ID INSULIN-RECEPTOR; LIFE-SPAN; POSTMENOPAUSAL WOMEN; FUNCTIONAL VARIANT; BONE-DENSITY; GENE; ASSOCIATION; LONGEVITY; MUTANT; POLYMORPHISMS AB A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals. C1 Univ Texas, SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA. Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Univ Tokyo, Dept Sensory & Motor Syst Med, Bunkyo Ku, Tokyo 1138655, Japan. Osaka Univ, Dept Internal Med & Mol Sci, Suita, Osaka 5650871, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, Boston, MA 02215 USA. RP Kuro-o, M (reprint author), Univ Texas, SW Med Ctr Dallas, Dept Pathol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM makoto.kuro-o@utsouthwestern.edu RI Takayama, Yoshiharu/E-3662-2010 FU NHLBI NIH HHS [R37 HL063762]; NIA NIH HHS [R01 AG019712, R01 AG019712-05, R01 AG025326, R01 AG025326-03, R01AG19712, R01AG25326]; NIDDK NIH HHS [U24 DK059637] NR 27 TC 743 Z9 799 U1 6 U2 55 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 SEP 16 PY 2005 VL 309 IS 5742 BP 1829 EP 1833 DI 10.1126/science.1112766 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 965ZN UT WOS:000231989500041 PM 16123266 ER PT J AU Watson, FL Puttmann-Holgado, R Thomas, F Lamar, DL Hughes, M Kondo, M Rebel, VI Schmucker, D AF Watson, FL Puttmann-Holgado, R Thomas, F Lamar, DL Hughes, M Kondo, M Rebel, VI Schmucker, D TI Extensive diversity of Ig-superfamily proteins in the immune system of insects SO SCIENCE LA English DT Article ID GENOMIC ANALYSIS; DROSOPHILA; RECEPTOR; DSCAM; EXPRESSION; GENES; DIVERSIFICATION; HEMOCYTES; DEFENSE; PATTERN AB The extensive somatic diversification of immune receptors is a hallmark of higher vertebrates. However, whether molecular diversity contributes to immune protection in invertebrates is unknown. We present evidence that Drosophila immune-competent cells have the potential to express more than 18,000 isoforms of the immunoglobulin (Ig)-superfamily receptor Down syndrome cell adhesion molecule (Dscam). Secreted protein isoforms of Dscam were detected in the hemolymph, and hemocyte-specific loss of Dscam impaired the efficiency of phagocytic uptake of bacteria, possibly due to reduced bacteria[ binding. Importantly, the molecular diversity of Dscam transcripts generated through a mechanism of alternative splicing is highly conserved across major insect orders, suggesting an unsuspected molecular complexity of the innate immune system of insects. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Neurobiol, Boston, MA 02115 USA. RP Schmucker, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Neurobiol, Boston, MA 02115 USA. EM dietmar_schmucker@dfci.harvard.edu RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NINDS NIH HHS [1RO1-NS46747-01] NR 23 TC 369 Z9 380 U1 7 U2 55 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 SEP 16 PY 2005 VL 309 IS 5742 BP 1874 EP 1878 DI 10.1126/science.1116887 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 965ZN UT WOS:000231989500055 PM 16109846 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI Personal view: passing the buck and taking a free ride - a game-theoretical approach to evasive management strategies in gastroenterology SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DECISION-MAKING AB Background: 'Free-riding' physicians enjoy the status, prestige and income of their profession without fully contributing to its overall mission. By shifting the costs of potential medical complications and difficult patient encounters to other physicians, they reap the benefits of their profession without carrying its full weight. Aim: To describe this phenomenon in terms of decision analysis and characterize the parameters affecting its occurrence. Methods: The interaction between two physicians is modeled as a non-zero-sum game. Two strategies of either contributing to patient management or taking a free ride are available to both physicians. The four possible outcomes are arranged in a two-by-two game matrix. Results: Physicians practice medicine because their personal benefit exceeds their cost. High cost to the physician results in a high probability of taking a free ride and copping out from potentially risky management. Increasing the benefit decreases the probability of free riding. As the number of possible encounters with other physicians increases, the probability of free riding increases and the probability for effective management by each individual physician decreases. Conclusion: If individual gastroenterologists felt less threatened by administrative repercussions and medico-legal consequences of untoward events, each one of them would contribute more to effective patient management. C1 Oregon Hlth & Sci Univ, Dept Gastroenterol, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Dept Gastroenterol, Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 18 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD SEP 15 PY 2005 VL 22 IS 6 BP 513 EP 518 DI 10.1111/j.1365-2036.2005.02627.x PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 963RY UT WOS:000231824800002 PM 16167967 ER PT J AU Ilkhanoff, L O'Donnell, CJ Camargo, CA O'Halloran, TD Giugliano, RP Lloyd-Jones, DM AF Ilkhanoff, L O'Donnell, CJ Camargo, CA O'Halloran, TD Giugliano, RP Lloyd-Jones, DM TI Usefulness of the TIMI risk index in predicting short- and long-term mortality in patients with acute coronary syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; THROMBIN INHIBITION; UNSTABLE ANGINA; INTIME-II; THROMBOLYSIS; HOSPITALIZATION; PROGNOSIS; HIRUDIN; TRIAL AB In a cohort of 710 patients with acute coronary syndromes (ACSs), we demonstrated that the Thrombolysis In Myocardial Infarction Risk Index-a predictor of 30-day mortality in clinical trial patients with ST-elevation myocardial infarction (STEMI -is a strong predictor of short- and long-term mortality with good discrimination ability (c statistics 0.77 to 0.79) among all subtypes of ACSs (STEMI, non-STEMI, and unstable angina pectoris). These results verify the utility of the Risk Index in unselected patients with STEMI, broaden its application to other types of ACSs, and extend its utility to stratification of long-term mortality risk. (c) 2005 Elsevier Inc. All rights reserved. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Cardiol, Dept Med, Chicago, IL 60611 USA. Hosp Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Blood Inst, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009 NR 12 TC 9 Z9 9 U1 0 U2 1 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 SEP 15 PY 2005 VL 96 IS 6 BP 773 EP 777 DI 10.1016/j.amjcard.2005.04.059 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967NA UT WOS:000232096700009 PM 16169358 ER PT J AU Cury, RC Pomerantsev, EV Ferencik, M Hoffmann, U Nieman, K Moselewski, F Abbara, S Jang, IK Brady, TJ Achenbach, S AF Cury, RC Pomerantsev, EV Ferencik, M Hoffmann, U Nieman, K Moselewski, F Abbara, S Jang, IK Brady, TJ Achenbach, S TI Comparison of the degree of coronary stenoses by multidetector computed tomography versus by quantitative coronary angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; DIAGNOSTIC-ACCURACY; RADIATION-EXPOSURE; IMAGE QUALITY; ARTERY; CT; LESIONS AB Sixteen-slice multidetector computed tomography (MDCT) and quantitative coronary angiography (QCA) were performed in 29 patients. Quantification of the degree of luminal narrowing and lesion length measurements were performed independently on MDCT and QCA at 42 sites with sufficient computed tomographic image quality. The correlation between MDCT and QCA for quantifying the degree of stenosis was excellent (r(2) = 0.93), although a systematic overestimation was observed by MDCT (bias 4% +/- 8%). The correlation between MDCT and QCA was moderate with respect to lesion length (r(2) = 0.54). In the absence of severe calcifications or motion artifacts, MDCT permits noninvasive quantification of coronary stenosis. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, Erlangen, Germany. RP Cury, RC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM rcury@partners.org NR 20 TC 48 Z9 54 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 SEP 15 PY 2005 VL 96 IS 6 BP 784 EP 787 DI 10.1016/j.amjcard.2005.05.020 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967NA UT WOS:000232096700012 PM 16169361 ER PT J AU Das, SR Dries, DL Drazner, MH Yancy, CW Chae, CU AF Das, SR Dries, DL Drazner, MH Yancy, CW Chae, CU TI Relation of lower hematocrit to progression from asymptomatic left ventricular dysfunction to symptomatic heart failure (from the studies of left ventricular dysfunction prevention trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PROGNOSTIC IMPACT; DIABETES-MELLITUS; RISK-FACTORS; ANEMIA; MORTALITY; INSIGHTS; DISEASE; SOLVD AB The relation between hematocrit and progression from asymptomatic left ventricular (LV) systolic dysfunction to symptomatic heart failure (HF) was examined in 2,821 patients from the Studies of Left Ventricular Dysfunction Prevention trial. Patients in the lowest hematocrit quartile (hematocrit <= 40%) were at increased risk for the development of HF symptoms (hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.37 to 2.34), first HF hospitalization (HR 2.35, 95% CI 1.52 to 3.62), and death or the development of HF symptoms (HR 1.60, 95 % CI 1.28 to 1.99) compared with patients in the highest hematocrit quartile (hematocrit > 46%). (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Div Cardiol, Heart Failure Res Grp, Dallas, TX 75230 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Das, SR (reprint author), Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75230 USA. EM sandeep.das@utsouthwestern.edu FU NHLBI NIH HHS [K23-HL004455, K08-HL-04154] NR 18 TC 8 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 SEP 15 PY 2005 VL 96 IS 6 BP 827 EP 831 DI 10.1016/j.amjcard.2005.05.030 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 967NA UT WOS:000232096700022 PM 16169371 ER PT J AU Aujesky, D Fine, MJ AF Aujesky, D Fine, MJ TI Does guideline adherence for empiric antibiotic therapy reduce mortality in community-acquired pneumonia? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID ANTIMICROBIAL THERAPY; MEDICAL OUTCOMES; ELDERLY-PATIENTS; MANAGEMENT; ADULTS C1 Univ Lausanne, CH-1015 Lausanne, Switzerland. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Aujesky, D (reprint author), Univ Lausanne, CH-1015 Lausanne, Switzerland. NR 16 TC 12 Z9 12 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 SEP 15 PY 2005 VL 172 IS 6 BP 655 EP 656 DI 10.1164/rccm.2506009 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 965AC UT WOS:000231921100001 PM 16148192 ER PT J AU Didenko, VV Ngo, H Baskin, DS AF Didenko, VV Ngo, H Baskin, DS TI Polyethyleneimine as a transmembrane carrier of fluorescently labeled proteins and antibodies SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE polyethyleneimine; PEI; protein delivery; avidin; Alexa avidin conjugates; lamin; glial cells; fibroblasts; antibody delivery; protein carrier; fluorescent detection ID BIOLOGICALLY-ACTIVE PROTEINS; GENE DELIVERY; MAMMALIAN-CELLS AB Polyethyleneimine (PEI) has been used previously as a nonviral DNA transfer vector. In this article, we demonstrate its use as a vehicle for transmembrane delivery of proteins in cell culture conditions. Linking proteins to PEI required no other treatment beyond mixing them with PEI. The bond between PEI and protein combined at optimal ratios was maintained in electrophoresis, even in the presence of 2.5% sodium dodecyl sulfate (SIDS). The optimal time for delivery of proteins was determined to be 24 h. We have successfully delivered an Alexa 488-labeled avidin protein into human glioblastoma cells. A functional antibody against the nuclear protein lamin was delivered into human fibroblasts and reacted with lamin inside live cells. PEI-based delivery of antibodies and fluorescently labeled proteins can be used for fluorescent detection, tracking, and evaluation of cellular protein function in vivo. (C) 2005 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Methodist Neurol Inst, Houston, TX 77030 USA. RP Didenko, VV (reprint author), Baylor Coll Med, Houston, TX 77030 USA. EM vdidenko@bcm.tmc.edu FU NIA NIH HHS [R03 AG022664] NR 12 TC 24 Z9 26 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 15 PY 2005 VL 344 IS 2 BP 168 EP 173 DI 10.1016/j.ab.2005.06.011 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 962XP UT WOS:000231767000002 PM 16095551 ER PT J AU Shnayderman, M Mansfield, B Yip, P Clark, HA Krebs, MD Cohen, SJ Zeskind, JE Ryan, ET Dorkin, HL Callahan, MV Stair, TO Gelfand, JA Gill, CJ Hitt, B Davis, CE AF Shnayderman, M Mansfield, B Yip, P Clark, HA Krebs, MD Cohen, SJ Zeskind, JE Ryan, ET Dorkin, HL Callahan, MV Stair, TO Gelfand, JA Gill, CJ Hitt, B Davis, CE TI Species-specific bacteria identification using differential mobility spectrometry and bioinformatics pattern recognition SO ANALYTICAL CHEMISTRY LA English DT Article ID AUTOMATED HEADSPACE CONCENTRATION; GAS-CHROMATOGRAPHY; VOLATILE METABOLITES; BUILDING-MATERIALS; PSEUDOMONAS-AERUGINOSA; PROTEOMIC PATTERNS; PULMONARY-DISEASE; FIELD-DEPENDENCE; SYNTHETIC MEDIA; OVARIAN-CANCER AB As bacteria grow and proliferate, they release a variety of volatile compounds that can be profiled and used for speciation, providing an approach amenable to disease diagnosis through quick analysis of clinical cultures as well as patient breath analysis. As a practical alternative to mass spectrometry detection and whole cell pyrolysis approaches, we have developed methodology that involves detection via a sensitive, micromachined differential mobility spectrometer (microDMx), for sampling head-space gases produced by bacteria growing in liquid culture. We have applied pattern discovery/recognition algorithms (ProteomeQuest) to analyze headspace gas spectra generated by microDMx to reliably discern multiple species of bacteria in vitro: Escherichia colt, Bacillus subtilis, Bacillus thuringiensis, and Mycobacterium smegmatis. The overall accuracy for identifying volatile profiles of a species within the 95% confidence interval for the two highest accuracy models evolved was between 70.4 and 89.3% based upon the coordinated expression of between 5 and 11 features. These encouraging in vitro results suggest that the microDMx technology, coupled with bioinformatics data analysis, has potential for diagnosis of bacterial infections. C1 Charles Stark Draper Lab Inc, Mech & Instruments Div, Bioengn Grp, Cambridge, MA 02139 USA. Correl Syst Inc, Bethesda, MD 20817 USA. Massachusetts Gen Hosp, Trop & Geog Med Ctr, Dept Immunol & Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Ctr Int Hlth & Dev, Boston, MA 02118 USA. RP Davis, CE (reprint author), Charles Stark Draper Lab Inc, Mech & Instruments Div, Bioengn Grp, 555 Technol Sq,MS37, Cambridge, MA 02139 USA. EM cdavis@draper.com RI Davis, Cristina/C-4437-2008; Clark, Heather/D-5247-2013; Krebs, Melissa/L-4878-2015; OI Krebs, Melissa/0000-0002-5170-7116; Mansfield, Brian/0000-0002-8533-2789 NR 49 TC 52 Z9 53 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 15 PY 2005 VL 77 IS 18 BP 5930 EP 5937 DI 10.1021/ac050348i PG 8 WC Chemistry, Analytical SC Chemistry GA 964ZL UT WOS:000231919400019 PM 16159124 ER PT J AU Nakamura, M McCarley, RW Kubicki, M Dickey, CC Niznikiewicz, MA Voglmaier, MM Seidman, LJ Maier, SE Westin, CF Kikinis, R Shenton, ME AF Nakamura, M McCarley, RW Kubicki, M Dickey, CC Niznikiewicz, MA Voglmaier, MM Seidman, LJ Maier, SE Westin, CF Kikinis, R Shenton, ME TI Fronto-temporal disconnectivity in schizotypal personality disorder: A diffusion tensor imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE diffusion tensor imaging; schizotypal personality disorder; uncinate fasciculus; cingulum bundle; fronto-temporal connectivity; fractional anisotropy ID UNCINATE FASCICLE SECTION; TEMPORAL GYRUS VOLUME; REGIONAL WHITE-MATTER; NEUROPATHOLOGICAL ABNORMALITIES; FUNCTIONAL CONNECTIVITY; PREFRONTAL CORTEX; ANTERIOR CINGULUM; ECHO-PLANAR; HUMAN BRAIN; SCHIZOPHRENIA AB Background: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD). Methods. Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D-m)were used to quantify; water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman's rho, followed by post hoc hierarchical regression analyses. Results. We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D-m measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect. and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance. Conclusions: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia. C1 Harvard Univ, Sch Med, Boston VA Healthcare Syst, Brockton Div,Dept Psychiat 116A,Lab Neurosci,Clin, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Magnet Resonance Imaging Div,Surg Planning Lab,De, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge Hosp, Cambridge Hlth Alliance,Dept Psychiat, Cambridge, MA 02138 USA. RP Shenton, ME (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, Brockton Div,Dept Psychiat 116A,Lab Neurosci,Clin, 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 NCRR NIH HHS [P41 RR013218]; NIBIB NIH HHS [U54 EB005149]; NIMH NIH HHS [R01 MH040799, 0R01 MH 50747, K02 MH 01110, K02 MH001110, K02 MH001110-10, R01 MH 40799, R03 MH068464, R03 MH068464-01] NR 84 TC 75 Z9 75 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2005 VL 58 IS 6 BP 468 EP 478 DI 10.1016/j.biopsych.2005.04.016 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 970HN UT WOS:000232296000007 PM 15978550 ER PT J AU Freeman, L Hewison, M Hughes, SV Evans, KN Hardie, D Means, TK Chakraverty, R AF Freeman, L Hewison, M Hughes, SV Evans, KN Hardie, D Means, TK Chakraverty, R TI Expression of 11 beta-hydroxysteroid dehydrogenase type 1 permits regulation of glucocorticoid bioavailability by human dendritic cells SO BLOOD LA English DT Article ID HEXOSE-6-PHOSPHATE DEHYDROGENASE; IN-VIVO; DIFFERENTIATION; INHIBITION; RECEPTOR; ACTIVATION; MATURATION; IL-10; CORTICOSTEROIDS; MODULATION AB Glucocorticoids (GCs) exert powerful anti-inflammatory effects that may relate in part to their ability to restrict the differentiation and function of dendritic cells (DCs). Although these inhibitory effects are dependent upon GCs binding to nuclear glucocorticoid receptors (GRs), fine-tuning of GR signaling is achieved by prereceptor interconversion of cortisol that binds GRs with high affinity and cortisone that does not. We show for the first time that human monocyte-derived DCs are able to generate cortisol as a consequence of up-regulated expression of the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). Immature DCs demonstrate selective enhancement of 11 beta-HSD1 reductase activity, leading to increased conversion of inactive cortisone to active cortisol. Enhancement of GC bioavailability is maintained or increased upon terminal differentiation induced by signals associated with innate immune activation. In marked contrast, maturation induced by CD40 ligation leads to a sharp reduction in cortisol generation by DCs. The differentiation of DCs from monocyte precursors is inhibited at physiologic concentrations of inactive cortisone, an effect that requires activity of the 11 beta-HSD1 enzyme. In conclusion, prereceptor regulation of endogenous GCs appears to be an important determinant of DC function and represents a potential target for therapeutic manipulation. C1 Univ Birmingham, Dept Hematol, Birmingham, W Midlands, England. Univ Birmingham, Dept Med Sci, Birmingham, W Midlands, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. RP Chakraverty, R (reprint author), UCL Royal Free & Univ Coll Med Sch, Rowland Hill St, London NW3 2PF, England. EM r.chakraverty@medsch.ucl.ac.uk NR 42 TC 49 Z9 50 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 SEP 15 PY 2005 VL 106 IS 6 BP 2042 EP 2049 DI 10.1182/blood-2005-01-0186 PG 8 WC Hematology SC Hematology GA 963PX UT WOS:000231817400032 PM 15941907 ER PT J AU Maki, K Yamagata, T Asai, T Yamazaki, L Oda, H Hirai, H Mitani, K AF Maki, K Yamagata, T Asai, T Yamazaki, L Oda, H Hirai, H Mitani, K TI Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; FETAL LIVER HEMATOPOIESIS; TRANSCRIPTION FACTOR PU.1; COLONY-STIMULATING FACTOR; T(3/21) FUSION PRODUCT; BINDING-PROTEIN-ALPHA; STEM-CELLS; GENE-EXPRESSION AB The AML1/EVI1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal translocation seen in patients with leukemic transformation of myelodysplastic syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the AML1/EVI1 chimeric gene into mouse AmI1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/EVI1/(+) embryo showed defective hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a result of hemorrhage in the central nervous system. The peripheral blood had yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. Although E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors from E13.5 AML1/ EVI1/(+) fetal liver were highly capable of self-renewal compared with those from wild-type liver. Maintained expression of PU.1 gene and decreased expression of LMO2 and SCL genes may explain the aberrant hematopoiesis in AML1/EVI1/(+) fetal liver. C1 Dokkyo Univ, Sch Med, Dept Hematol, Mibu, Tochigi 3210293, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Tokyo, Japan. Inoue Mem Hosp, Dept Clin Lab & Pathol, Chiba, Japan. Tokyo Womens Med Univ, Dept Pathol, Tokyo, Japan. RP Mitani, K (reprint author), Dokkyo Univ, Sch Med, Dept Hematol, 880 Kitakobayashi, Mibu, Tochigi 3210293, Japan. EM kinukom-tky@umin.ac.jp NR 61 TC 10 Z9 11 U1 1 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 SEP 15 PY 2005 VL 106 IS 6 BP 2147 EP 2155 DI 10.1182/blood-2004-11-4330. PG 9 WC Hematology SC Hematology GA 963PX UT WOS:000231817400046 PM 15914564 ER PT J AU Chng, WJ Van Wier, SA Ahmann, GJ Winkler, JM Jalal, SM Bergsagel, PL Chesi, M Trendle, MC Oken, MM Blood, E Henderson, K Santana-Davila, R Kyle, RA Gertz, MA Lacy, MQ Dispenzieri, A Greipp, PR Fonseca, R AF Chng, WJ Van Wier, SA Ahmann, GJ Winkler, JM Jalal, SM Bergsagel, PL Chesi, M Trendle, MC Oken, MM Blood, E Henderson, K Santana-Davila, R Kyle, RA Gertz, MA Lacy, MQ Dispenzieri, A Greipp, PR Fonseca, R TI A validated FISH trisony index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS SO BLOOD LA English DT Article ID IN-SITU HYBRIDIZATION; PLASMA-CELL LEUKEMIA; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; CHROMOSOMAL-ABNORMALITIES; 14Q32 TRANSLOCATIONS; DISEASE PROGRESSION; DNA; GENE AB Two major genetic categories of multiple myeloma (MM) exist. Hyperdiploid MM (48 to 74 chromosomes, median 53 chromosomes) is associated with trisomies especially of chromosomes 3,7,9,11,15, and 19, whereas the nonhyperdiploid (< 48 chromosomes or more than 74 chromosomes) MM is associated with primary translocations such as t(11;14), t(4;14), and t(14;16). Whether this dichotomy exists in monoclonal gammopathy of undetermined significance (MGUS) is uncertain due to limitations of current methods in the study of ploidy. This is especially true in MGUS where the number of clonal plasma cells is small. In this study, we derived a fluorescent in situ hybridization (FISH)-based trisomy index from pooled cytogenetic data (karyotype analysis) from 2 large cohorts of patients with MM with abnormal karyotype, and then validated it in 2 independent cohorts of patients who had known ploidy status either by karyotyping or DNA content measurement using flow cytometry. Using the criteria of 2 or more trisomies from a 3-chromosome combination, hyperdiploid myeloma can be detected with high specificity. Applying this index on 28 patients with smoldering multiple myeloma (SMM) or MGUS (11 SMM, 17 MGUS) who had normal karyotype, 11 cases of hyperdiploid SMM/MGUS were detected. This percentage (40%) is remarkably similar to the percentage of hyperdiploid MM reported in the literature, suggesting that hyperdiploid MM may originate early during disease evolution. C1 Mayo Clin Scottsdale, Ctr Comprehens Canc, Scottsdale, AZ USA. Mayo Clin Scottsdale, Div Hematol & Oncol, Scottsdale, AZ USA. Natl Univ Singapore Hosp, Dept Haematol Oncol, Singapore 119074, Singapore. Mayo Clin Rochester, Div Hematol, Rochester, MN USA. Mayo Clin Rochester, Dept Lab Med & Pathol, Rochester, MN USA. Missouri Canc Associates, Columbia, MO USA. N Mem Canc Ctr, Robbinsdale, MN USA. ECOG, Ctr Stat, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fonseca, R (reprint author), 13 400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM fonseca.rafael@mayo.edu RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA21 115-25C, P01 CA62 242, P50 CA100 707-01, R01 CA83 724 01] NR 45 TC 71 Z9 74 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2005 VL 106 IS 6 BP 2156 EP 2161 DI 10.1182/blood-2005-02-0761. PG 6 WC Hematology SC Hematology GA 963PX UT WOS:000231817400047 PM 15920009 ER PT J AU Chen, W Arroyo, JD Timmons, JC Possemato, R Hahn, WC AF Chen, W Arroyo, JD Timmons, JC Possemato, R Hahn, WC TI Cancer-associated PP2A A alpha subunits induce functional haploinsufficiency and tumorigenicity SO CANCER RESEARCH LA English DT Article ID PROTEIN PHOSPHATASE 2A; SMALL-T-ANTIGEN; HUMAN CELL-TRANSFORMATION; SMALL TUMOR-ANTIGEN; REGULATORY SUBUNITS; PPP2R1B GENE; COLORECTAL CANCERS; REDUCED EXPRESSION; CATALYTIC SUBUNIT; SIMIAN VIRUS-40 AB The introduction of SV40 small t antigen or the suppression of PP2A B56 gamma subunit expression contributes to the experimental transformation of human cells. To investigate the role of cancer-associated PP2A A alpha subunit mutants in transformation, we introduced several PP2A A alpha mutants into immortalized but nontumorigenic human cells. These PP2A A alpha mutants exhibited defects in binding to other PP2A subunits and impaired phosphatase activity. Although overexpression of these mutants failed to render immortalized cells tumorigenic, partial suppression of endogenous PP2A A alpha expression activated the AKT pathway and permitted cells to form tumors in immunodeficient mice. These findings suggest that cancer-associated A alpha mutations contribute to cancer development by inducing functional haploinsufficiency, disturbing PP2A holoenzyme composition, and altering the enzymatic activity of PP2A. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Zhongshan Univ, Sch Publ Hlth, Dept Toxicol, Guangzhou, Peoples R China. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 710C, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu FU NCI NIH HHS [K01 CA94223, P01 CA50661] NR 49 TC 86 Z9 90 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2005 VL 65 IS 18 BP 8183 EP 8192 DI 10.1158/0008-5472.CAN-05-1103 PG 10 WC Oncology SC Oncology GA 964AQ UT WOS:000231848800018 PM 16166293 ER PT J AU Tang, Y Kim, M Carrasco, D Kung, AL Chin, L Weissleder, R AF Tang, Y Kim, M Carrasco, D Kung, AL Chin, L Weissleder, R TI In vivo assessment of RAS-dependent maintenance of tumor angiogenesis by real-time magnetic resonance imaging SO CANCER RESEARCH LA English DT Article ID CANCER; TUMORIGENESIS; MICROSCOPY; CONTRAST; MICE AB New blood vessel formation is a prominent feature of human cancers and tumor progression and is frequently accompanied by the acquisition of an angiogenic phenotype associated with a switch in the balance of proangiogenic and antiangiogenic molecules. This study was designed to investigate the role of activated H-RAS on the angiogenic phenotype of melanoma that arises in the inducible Tyr/Tet-RAS Ink4a/Arf(-/-) model using in vivo imaging with histopathologic correlation. We show that loss of RAS activity in fully established melanomas led to a reduction in tumor volume, which was preceded by impairment of vascular function as determined by in vivo magnetic resonance imaging. This correlated with activation of apoptosis in host-derived endothelial cells as well as in tumor cells. Thus, real-time in vivo imaging provided evidence that maintenance of tumor angiogenesis requires activated RAS in this model system, and that loss of vascular integrity upon inactivation of RAS is an active process rather than a consequence of loss of tumor cell viability. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M413, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu; weissleder@helix-mgh.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [P50 CA86355, R01 CA93947, R24 CA92782, U01 CA84313]; NIA NIH HHS [1K 08AG01031-02] NR 17 TC 27 Z9 28 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2005 VL 65 IS 18 BP 8324 EP 8330 DI 10.1158/0008-5472.CAN-05-0027 PG 7 WC Oncology SC Oncology GA 964AQ UT WOS:000231848800034 PM 16166309 ER PT J AU Chauhan, D Li, GL Podar, K Hideshima, T Neri, P He, DL Mitsiades, N Richardson, P Chang, Y Schindler, J Carver, B Anderson, KC AF Chauhan, D Li, GL Podar, K Hideshima, T Neri, P He, DL Mitsiades, N Richardson, P Chang, Y Schindler, J Carver, B Anderson, KC TI A novel carbohydrate-based therapeutic GCS-100 overcomes bortezomib resistance and enhances dexamethasone-induced apoptosis in multiple myeloma cells SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; INHIBITOR PS-341 RESISTANCE; MODIFIED CITRUS PECTIN; MARROW STROMAL CELLS; BONE-MARROW; OLIGONUCLEOTIDE ARRAYS; SIGNAL-TRANSDUCTION; LUNG COLONIZATION; DRUG-RESISTANCE; HUMAN CANCER AB Human multiple myeloma is a presently incurable hematologic malignancy, and novel biologically based therapies are urgently needed. GCS-100 is a polysaccharide derived from citrus pectin in clinical development for the treatment of cancer. Here we show that GCS-100 induces apoptosis in various multiple myeloma cell lines, including those resistant to dexamethasone, melphalan, or doxorubicin. Examination of purified patient multiple myeloma cells showed similar results. Specifically, GCS-100 decreases viability of bortezomib/PS-341 -resistant multiple myeloma patient cells. Importantly, GCS-100 inhibits multiple myeloma cell growth induced by adhesion to bone marrow stromal cells; overcome the growth advantage conferred by antiapoptotic protein Bcl-2, heat shock protein-27, and nuclear factor-kappa B; and blocks vascular endothelial growth factor-induced migration of multiple myeloma cells. GCS-100-induced apoptosis is associated with activation of caspase-8 and caspase-3 followed by proteolytic cleavage of poly(ADP-ribose) polymerase enzyme. Combined with dexamethasone, GCS-100 induces additive anti-multiple myeloma cytotoxicity associated with mitochondrial apoptotic signaling via release of cytochrome c and Smac followed by activation of caspase-3. Moreover, GCS-100 + dexamethasone-induced apoptosis in multiple myeloma cells is accompanied by a marked inhibition of an antiapoptotic protein Galectin-3, without significant alteration in Bcl-2 expression. Collectively, these findings provide the framework for clinical evaluation of GCS-100, either alone or in combination with dexamethasone, to inhibit tumor growth, overcome drug resistance, and improve outcome for patients with this universally fatal hematologic malignancy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. GlycoGenesys Inc, Boston, MA 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 [CA 50947, CA 78373, CA100707] NR 49 TC 73 Z9 83 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2005 VL 65 IS 18 BP 8350 EP 8358 DI 10.1158/0008-5472.CAN-05-0163 PG 9 WC Oncology SC Oncology GA 964AQ UT WOS:000231848800037 PM 16166312 ER PT J AU Zerbini, LF Libermann, TA AF Zerbini, LF Libermann, TA TI GADD45 deregulation in cancer: Frequently methylated tumor suppressors and potential therapeutic targets SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID DNA METHYLATION; CPG ISLANDS; HEPATOCELLULAR-CARCINOMA; EXPRESSION; GROWTH; GENES; BINDING; CELLS; IDENTIFICATION; INDUCTION C1 Beth Israel Deaconess Med Ctr, Genom Ctr, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr Canc Proteom Core, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Libermann, TA (reprint author), Beth Israel Deaconess Med Ctr, Genom Ctr, 4 Blackfan Circle, Boston, MA 02115 USA. EM tliberma@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; Zerbini, Luiz /B-7720-2015; OI Libermann, Towia/0000-0002-4006-8179 NR 25 TC 30 Z9 31 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 SEP 15 PY 2005 VL 11 IS 18 BP 6409 EP 6413 DI 10.1158/1078-0432.CCR-05-1475 PG 5 WC Oncology SC Oncology GA 966JN UT WOS:000232016100001 PM 16166414 ER PT J AU Ogino, S Meyerhardt, JA Cantor, M Brahmandam, M Clark, JW Namgyal, C Kawasaki, T Kinsella, K Michelini, AL Enzinger, PC Kulke, MH Ryan, DP Loda, M Fuchs, CS AF Ogino, S Meyerhardt, JA Cantor, M Brahmandam, M Clark, JW Namgyal, C Kawasaki, T Kinsella, K Michelini, AL Enzinger, PC Kulke, MH Ryan, DP Loda, M Fuchs, CS TI Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; PHASE-II TRIAL; ANTITUMOR-ACTIVITY; ZD1839 IRESSA; CYCLOOXYGENASE-2 INHIBITOR; SOMATIC MUTATIONS; CARCINOMA-CELLS; EGFR MUTATIONS AB Purpose: Recently, activating mutations of the epidermal, growth factor- receptor (EGFR) gene 9 I e discovered in, non -small cell lung- cancers sensitive to gefftinib, (ZD1839, an EGFR tyro-. sine kinase inhibitor) but I not in gefitinib-resistant cancers. Abnormalities of EGFR and related pathways may,have an effect on responsiveness of advanced,colorectal cancer to combination chemotherapy with gefitinib. Experimental- Design: We examined, patients with 'previously untreated metastatic colorectal cancer,who were enrolled into two phase I/II trials of combination chemotherapy (irinotecan, leucovorin, and 5-fluorouracil) and daily- oral gefitinib. We obtained paraffin tissue blocks of primary tumors from 31 patients, sequenced the,EGFR, KRAS and BRAF genes, and did immunohistochemistry for EGFR, phosphohorylated AKT1- p53, p21, and p27. Results: Twelve (39%) of the 31 patients experienced. a partial objective response to the therpy ) was identified in only one apy. A novel EGFR -mutation in exon 18 (c. 21760G>A, p,Gly724Ser) patient who did not experience an objective tumor response. EGFR immunohistochemistry Was not predictive. of responsiveness. In contrast,loss of p21 was associated with a higher 'response rate to therapy (P= 0.05). Moreover the response rate among patients whose tumors maintained p21 expression and possessed a mutation in p53 was' only 9% (1 of 11, P = 0.005). Overexpresssion of phosphorylated AKT1 also seemed to predict a trend towards resistance, to the therapy. Conclusions: p21 expression in colorectal cancer, especially in combination with p53 mutation, is a predictor of resistance to the combination chemotherapy with gefitinib. Activating EGFR to confer sensitivity to gefitinib and mutations are, rare. in colorectal cancer and do not seem chemotherapy. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Room D318,44 Binney St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075-13, P01 CA87969-03] NR 38 TC 106 Z9 111 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2005 VL 11 IS 18 BP 6650 EP 6656 DI 10.1158/1078-0432.CCR-05-0738 PG 7 WC Oncology SC Oncology GA 966JN UT WOS:000232016100031 PM 16166444 ER PT J AU Kramer-Zucker, AG Wiessner, S Jensen, AM Drummond, IA AF Kramer-Zucker, AG Wiessner, S Jensen, AM Drummond, IA TI Organization of the pronephric filtration apparatus in zebrafish requires Nephrin, Podocin and the FERM domain protein Mosaic eyes SO DEVELOPMENTAL BIOLOGY LA English DT Article DE kidney development; podocyte; pronephros; slit diaphragm; zebrafish ID CONGENITAL NEPHROTIC SYNDROME; SLIT DIAPHRAGM; MICE LACKING; CD2-ASSOCIATED PROTEIN; GLOMERULAR PODOCYTE; ACTIN CYTOSKELETON; JUNCTION FORMATION; ADHERENS JUNCTION; RENAL-DISEASE; P120 CATENIN AB Podocytes are specialized cells of the kidney that form the blood filtration barrier in the kidney glomerulus. The barrier function of podocytes depends upon the development of specialized cell-cell adhesion complexes called slit-diaphragms that form between podocyte foot processes surrounding glomerular blood vessels. Failure of the slit-diaphragm to form results in leakage of high molecular weight proteins into the blood filtrate and urine, a condition called proteinuria. In this work, we test whether the zebrafish pronephros can be used as an assay system for the development of glomerular function with the goal of identifying novel components of the slit-diaphragm. We first characterized the function of the zebrafish homolog of Nephrin, the disease gene associated with the congenital nephritic syndrome of the Finnish type, and Podocin, the gene mutated in autosomal recessive steroid-resistant nephrotic syndrome. Zebrafish nephrin and podocin were specifically expressed in pronephric podocytes and required for the development of pronephric podocyte cell structure. Ultrastructurally, disruption of nephrin or podocin expression resulted in a loss of slit-diaphragms at 72 and 96 h post-fertilization and failure to form normal podocyte foot processes. We also find that expression of the band 4.1/FERM domain gene mosaic eyes in podocytes is required for proper formation of slit-diaphragm cell-cell junctions. A functional assay of glomerular filtration barrier revealed that absence of normal nephrin, podocin or mosaic eyes expression results in loss of glomerular filtration discrimination and aberrant passage of high molecular weight substances into the glomerular filtrate. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149-8000,149 13th St, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NEI NIH HHS [R01 EY015420-02, R01 EY015420-04, R01 EY015420-01, R01 EY015420-03]; NICHD NIH HHS [R01 HD/DK53093]; NIDDK NIH HHS [R01 DK053093] NR 59 TC 101 Z9 106 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2005 VL 285 IS 2 BP 316 EP 329 DI 10.1016/j.ydbio.2005.06.038 PG 14 WC Developmental Biology SC Developmental Biology GA 974ES UT WOS:000232574700003 PM 16102746 ER PT J AU zur Wiesch, JS Lauer, GM Day, CL Kim, AY Ouchi, K Duncan, JE Wurcel, AG Timm, J Jones, AM Mothe, B Allen, TM McGovern, B Lewis-Ximenez, L Sidney, J Sette, A Chung, RT Walker, BD AF zur Wiesch, JS Lauer, GM Day, CL Kim, AY Ouchi, K Duncan, JE Wurcel, AG Timm, J Jones, AM Mothe, B Allen, TM McGovern, B Lewis-Ximenez, L Sidney, J Sette, A Chung, RT Walker, BD TI Broad repertoire of the CD4(+) th cell response in spontaneously controlled hepatitis C virus infection includes dominant and highly promiscuous epitopes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II TETRAMERS; CHRONIC VIRAL-INFECTIONS; EX-VIVO ANALYSIS; PRIMERS PCR-SSP; LYMPHOCYTE EPITOPES; HLA-B; NONSTRUCTURAL PROTEIN-3; COMPREHENSIVE ANALYSIS; IMMUNE-RESPONSES; PEPTIDE BINDING AB A vigorous hepatitis C virus (HCV)-specific Th cell response is regarded as essential to the immunological control of HCV viremia. The aim of this study was to comprehensively define the breadth and specificity of dominant HCV-specific CD4(+) T cell epitopes in large cohorts of subjects with chronic and spontaneously resolved HCV viremia. Following in vitro stimulation of PBMC, HCV-specific cell cultures from each subject were screened with an overlapping panel of synthetic 20-mer peptides spanning the entire HCV polyprotein. Of 22 subjects who spontaneously controlled HCV viremia, all recognized at least one of a group of six epitopes situated within the nonstructural (NS) proteins NS3, NS4, and NS5, each of which was detected by > 30% of subjects, but most subjects recognized additional, more heterogeneous specificities. In contrast, none of the most frequently targeted epitopes was detected by > 5% of persons with chronic infection. The most frequently recognized peptides showed promiscuous binding to multiple HLA-DR molecules in in vitro binding assays and were restricted by different HLA-DR molecules in functional assays in different persons. These data demonstrate that predominant CD4(+) T cell epitopes in persons with resolved HCV infection are preferentially located in the nonstructural proteins and are immunogenic in the context of multiple class 11 molecules. This comprehensive characterization of CD4(+) T cell epitopes in resolved HCV infection provides important information to facilitate studies of immunopathogenesis and HCV vaccine design and evaluation. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Calif State Univ, Dept Biol Sci, San Marcos, CA 92096 USA. Lemuel Shattuck Hosp, Jamaica Plain, MA 02108 USA. Inst Oswaldo Cruz, FIOCRUZ, Dept Virol, BR-20001 Rio De Janeiro, RJ, Brazil. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, 149 13th St,Room 5212D, Boston, MA 02129 USA. EM bwalker@partners.org RI Day, Cheryl/J-9844-2012; Allen, Todd/F-5473-2011 NR 58 TC 96 Z9 98 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 SEP 15 PY 2005 VL 175 IS 6 BP 3603 EP 3613 PG 11 WC Immunology SC Immunology GA 966HN UT WOS:000232010800022 ER PT J AU Matute-Bello, G Lee, JS Liles, WC Frevert, CW Mongovin, S Wong, V Ballman, K Sutlief, S Martin, TR AF Matute-Bello, G Lee, JS Liles, WC Frevert, CW Mongovin, S Wong, V Ballman, K Sutlief, S Martin, TR TI Fas-mediated acute lung injury requires Fas expression on nonmyeloid cells of the lung SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; FAS/FAS LIGAND SYSTEM; PROTEIN PERMEABILITY; PULMONARY-FIBROSIS; EPITHELIAL-CELLS; SOLUBLE FORM; APOPTOSIS; MICE; INDUCTION; HUMANS AB Fas (CD95) is a membrane surface receptor, which, in the lungs, is expressed in macrophages, neutrophils, and epithelial cells. In mice, Fas activation leads to a form of lung injury characterized by increased alveolar permeability. We investigated whether Fas-mediated lung injury occurs primarily as a result of Fas activation in myeloid cells (such as macrophages) or in nommyeloid cells (such as epithelial cells). Chimeric mice lacking Fas in either myeloid or nonmyeloid cells were generated by transplanting marrow cells from lpr mice (which lack Fas) into lethally irradiated C57BL/6 mice (MyFas(-) group) or vice versa (MyFas(+) group). Additional mice transplanted with marrow cells from their same strain served as controls (Fas(+) ctr and Fas(-) ctr groups). Sixty days after transplantation, the mice received intratracheal instillations of the Fas-activating mAb Jo2 (n = 10/group), or an isotype control Ab (n = 10/group), and were euthanized 24-h later. Only animals expressing Fas in nonmyeloid cells (Fas(+) ctr and MyFas-) showed significant increases in lung neutrophil content and in alveolar permeability. These same mice showed tissue evidence of lung injury and caspase-3 activation in cells of the alveolar walls. Despite differences in the neutrophilic response and lung injury, there was no statistical difference in the lung cytokine concentrations (KC and MIP-2) among groups. We conclude that Fas-mediated lung injury requires expression of Fas on nonmyeloid cells of the lungs. These findings suggest that the alveolar epithelium is the primary target of Fas-mediated acute lung injury, and demonstrate that apoptotic processes may be associated with neutrophilic inflammation. C1 Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA. Vet Affairs Puget Sound Healthcare Syst, Med Res Serv, Seattle, WA 98108 USA. Vet Affairs Puget Sound Healthcare Syst, Sect Radiat Oncol, Seattle, WA 98108 USA. RP Matute-Bello, G (reprint author), 1660 S Columbian Way,GMR 151-L, Seattle, WA 98108 USA. EM matuteb@u.washington.edu FU NHLBI NIH HHS [HL62995, HL70178, HL70840, HL73966] NR 33 TC 35 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2005 VL 175 IS 6 BP 4069 EP 4075 PG 7 WC Immunology SC Immunology GA 966HN UT WOS:000232010800074 PM 16148156 ER PT J AU Offner, H Subramanian, S Wang, CH Afentoulis, M Vandenbark, AA Huan, JY Burrows, GG AF Offner, H Subramanian, S Wang, CH Afentoulis, M Vandenbark, AA Huan, JY Burrows, GG TI Treatment of passive experimental autoimmune encephalomyelitis in SJL mice with a recombinant TCR ligand induces IL-13 and prevents axonal injury SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-II; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ENCEPHALITOGENIC T-CELLS; BOUND SINGLE PEPTIDES; MULTIPLE-SCLEROSIS; MYASTHENIA-GRAVIS; RECEPTOR LIGANDS; TH1 CELLS; COMPLEXES; ACTIVATION AB The major goal of this study was to evaluate the efficacy and mechanism of a rTCR ligand (RTL) construct (I-A(S)/proteolipid protein (PLP)-139-151 peptide = RTL401) for treatment of SJL/J mice developing passive experimental autoimmune encephalomyelitis (EAE) that did not involve coimmunization with the highly inflammatory CFA. Our results demonstrated clearly that RTL401 was highly effective in treating passive EAE, with kinetics of recovery from disease very similar to treatment of actively induced EAE. The potent RTL401 treatment effect was reflected by a partial reduction of infiltrating mononuclear cells into CNS, minimal inflammatory lesions in spinal cord, and preservation of axons injured in vehicle-treated mice during the progression of EAE. Interestingly, in the absence of CFA, RTL401 treatment strongly enhanced production of the Th2 cytokine, IL-13, in spleen, blood, and spinal cord tissue, with variable effects on other Th1 and Th2 cytokines, and no significant effect on the TH cytokine, TGF-beta 1, or on FoxP3 that is expressed by regulatory T cells. Moreover, pretreatment of PLP-139-151-specific T cells with RTL401 in vitro induced high levels of secreted IL-13, with lesser induction of other pro- and anti-inflammatory cytokines. Given the importance of IL-13 for protection against EAE, these data strongly implicate IL-13 as a dominant regulatory cytokine induced by RTL therapy. Pronounced IL-13 levels coupled with marked reduction in IL-6 levels secreted by PLP-specitic T cells from blood after treatment of mice with RTL401 indicate that IL-13 and IL-6 may be useful markers for following effects of RTL therapy in future clinical trials in multiple sclerosis. C1 Portland Vet Affairs 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 Anesthesiol & Perioperat Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland Vet Affairs 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 [AI43960]; NINDS NIH HHS [NS23444, NS41965, NS46877, NS47661] NR 37 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2005 VL 175 IS 6 BP 4103 EP 4111 PG 9 WC Immunology SC Immunology GA 966HN UT WOS:000232010800078 PM 16148160 ER PT J AU Bryant, AE Bayer, CR Chen, RYZ Guth, PH Wallace, RJ Stevens, DL AF Bryant, AE Bayer, CR Chen, RYZ Guth, PH Wallace, RJ Stevens, DL TI Vascular dysfunction and ischemic destruction of tissue in streptococcus pyogenes infection: The role of streptolysin O - Induced platelet/neutrophil complexes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 30-OCT 03, 2004 CL Boston, MA SP Infect Dis Soc Amer ID PLATELET-ACTIVATING-FACTOR; CLOSTRIDIAL GAS-GANGRENE; LEUKOCYTE INTERACTION; ADHERENT PLATELETS; ORGAN DYSFUNCTION; PHOSPHOLIPASE-C; P-SELECTIN; NEUTROPHIL; ACCUMULATION; PERFRINGENS AB Rapid tissue destruction in group A streptococcal (GAS) necrotizing fasciitis/myonecrosis often necessitates extensive debridement to ensure survival. The mechanisms responsible for this fulminant process remain unknown; we hypothesized that toxin-induced ischemia contributes to necrosis. In a rat model, Doppler flowmetry was used to measure local blood flow at the site of the intramuscular injection of exotoxins from an invasive M-type 1 GAS, which caused a rapid, dose-dependent decrease in perfusion that was irreversible at the highest toxin concentration tested. Videomicroscopic results revealed that blood flow was impeded by occlusive intravascular cellular aggregates. Flow-cytometric results confirmed that GAS toxins induced the coaggregation of platelets and neutrophils, that this activity was attributable to streptolysin O, and that platelet/neutrophil complex formation was largely mediated by platelet P-selectin (CD62P). Strategies that target platelet adherence molecules may prevent vascular occlusion, maintain tissue viability, and reduce the need for amputation in necrotizing GAS infections. C1 Dept Vet Affairs Med Ctr, Res & Dev Serv, Infect Dis Sect, Boise, ID 83702 USA. Univ Idaho, Moscow, ID 83843 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Anesthesiol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Bryant, AE (reprint author), Dept Vet Affairs Med Ctr, Res & Dev Serv, Infect Dis Sect, 500 W Ft St,Bldg 45, Boise, ID 83702 USA. EM bryant@mindspring.com FU NCRR NIH HHS [P20RR15587] NR 28 TC 42 Z9 42 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2005 VL 192 IS 6 BP 1014 EP 1022 DI 10.1086/432729 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 960WJ UT WOS:000231623600011 PM 16107954 ER PT J AU Stone, ME AF Stone, ME TI Handbook of epidemiology SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD SEP 15 PY 2005 VL 130 IS 15 BP 92 EP 92 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 967XF UT WOS:000232123800242 ER PT J AU Molyneaux, BJ Arlotta, P Hirata, T Hibi, M Macklis, JD AF Molyneaux, BJ Arlotta, P Hirata, T Hibi, M Macklis, JD TI Fezl is required for the birth and specification of corticospinal motor neurons SO NEURON LA English DT Article ID ZINC-FINGER GENE; CEREBRAL CORTICAL DEVELOPMENT; CELL FATE SPECIFICATION; CENTRAL-NERVOUS-SYSTEM; NEOCORTICAL NEURONS; ZEBRAFISH FOREBRAIN; SUBVENTRICULAR ZONE; SUBCORTICAL TARGETS; LAYER NEURONS; AREA IDENTITY AB The molecular mechanisms controlling the differentiation of neural progenitors into distinct subtypes of neurons during neocortical development are unknown. Here, we report that Fezl is required for the specification of corticospinal motor neurons and other subcerebral projection neurons, which are absent from Fezl null mutant neocortex. There is neither an increase in cell death in Fezl(-/-) cortex nor abnormalities in migration, indicating that the absence of subcerebral projection neurons is due to a failure in fate specification. In striking contrast, other neuronal populations in the same and other cortical layers are born normally. Overexpression of Fezl results in excess production of subcerebral projection neurons and arrested migration of these neurons in the germinal zone. These data indicate that Fezl plays a central role in the specification of corticospinal motor neurons and other subcerebral projection neurons, controlling early decisions regarding lineage-specific differentiation from neural progenitors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Neurosci, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. RIKEN, Ctr Dev Biol, Lab Vertebrate Axis Format, Kobe, Hyogo, Japan. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Neurosci, MGH HMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu OI Molyneaux, Bradley/0000-0002-3377-1229 FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS41590, NS45523, NS49553] NR 56 TC 257 Z9 264 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 15 PY 2005 VL 47 IS 6 BP 817 EP 831 DI 10.1016/j.neuron.2005.08.030 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 967IN UT WOS:000232085000010 PM 16157277 ER PT J AU Wolf, M Harris, NL Smith, RN Rose, H McCluskey, RT AF Wolf, M Harris, NL Smith, RN Rose, H McCluskey, RT TI A 42-year-old man with weight loss, weakness, and a rash - Necrotizing glomerulonephritis and tubulointerstitial nephritis with antibodies to myeloperoxidase; renal involvement by the Churg-Strauss syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VASCULITIS; HEMORRHAGE; TESTS C1 Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Berkshire Med Ctr, Dept Med, Div Nephrol, Pittsfield, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wolf, M (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 15 PY 2005 VL 353 IS 11 BP 1148 EP 1157 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 963YG UT WOS:000231841900011 PM 16162886 ER PT J AU Blumenthal, D Hsiao, W AF Blumenthal, D Hsiao, W TI Privatization and its discontents - The evolving Chinese health care system SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MARKET; REFORM C1 Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. NR 22 TC 264 Z9 274 U1 4 U2 36 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 15 PY 2005 VL 353 IS 11 BP 1165 EP 1170 DI 10.1056/NEJMhpr051133 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 963YG UT WOS:000231841900014 PM 16162889 ER PT J AU Miklowitz, DJ Wisniewski, SR Miyahara, S Otto, MW Sachs, GS AF Miklowitz, DJ Wisniewski, SR Miyahara, S Otto, MW Sachs, GS TI Perceived criticism from family members as a predictor of the one-year course of bipolar disorder SO PSYCHIATRY RESEARCH LA English DT Article DE expressed emotion; psychosocial treatment; course of illness; depression; family therapy; environmental stress ID SCHIZOPHRENIA SPECTRUM DISORDERS; EXPRESSED EMOTION; AFFECTIVE STYLE; LIFE EVENTS; RELAPSE; DEPRESSION; VALIDITY; THERAPY; STRESS; SCALE AB Few studies have examined the prognostic value of family factors in the course of bipolar affective disorder. The current study examined a self-report measure of expressed emotion as a predictor of the I-year course of the illness. Patients with bipolar disorder (N=360) filled out the four-item Perceived Criticism Scale concerning one or more relatives or close friends. Independent evaluators followed patients over I year and rated them on measures of depressive and manic symptoms and the percentage of days in recovery status. Patients' ratings of the severity of criticisms from relatives did not predict patients' mood disorder symptoms at follow-up. However, patients who were more distressed by their relatives' criticisms had more severe depressive and manic symptoms and proportionately fewer days well during the study year than patients who were less distressed by criticisms. Patients who reported that their relatives became more upset by the patients' criticisms had less severe depressive symptoms at follow-up. Results indicate that a brief rating of subjective distress in response to familial criticism is a useful prognostic device and may aid in planning psychosocial interventions for patients with bipolar disorder. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Miklowitz, DJ (reprint author), Univ Colorado, Dept Psychol, Muenzinger Bldg, Boulder, CO 80309 USA. EM miklow@psych.colorado.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 37 TC 46 Z9 47 U1 2 U2 18 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 SEP 15 PY 2005 VL 136 IS 2-3 BP 101 EP 111 DI 10.1016/j.psychres.2005.04.005 PG 11 WC Psychiatry SC Psychiatry GA 970FX UT WOS:000232291700003 PM 16023735 ER PT J AU Lieu, SN Million, M Oh, DS Waschek, JA Tache, Y Pisegna, JR Germano, PM AF Lieu, SN Million, M Oh, DS Waschek, JA Tache, Y Pisegna, JR Germano, PM TI PACAP and its receptor, PAC(1) exert a protective effect in preventing dextran sulfate sodium (DSS)-induced colitis SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 7th International Symposium on VIP, PACAP and Related Peptides CY SEP 11-14, 2005 CL Rouen, FRANCE SP Conseil Reg Haute-Normandie, Agglomerat Rouen, Inst Fed Rech Multidisciplinaires Peptides, Inst Natl Sante Rech Med, Municipal Rouen, Sci Act Haute-Normandie, Tech Chime-Biol Sante, Univ Paris 7, Univ Rouen C1 VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 15 PY 2005 VL 130 IS 3 BP 168 EP 169 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 959OL UT WOS:000231527400097 ER PT J AU Lieu, SN Oh, DS Lambrecht, N Yakubov I Sachs, G Pisegna Jr Germano, PM AF Lieu, SN Oh, DS Lambrecht, N Yakubov, I Sachs, G Pisegna, JR Germano, PM TI PACAP activation of secretory and proliferative signaling pathways in BON cells is mediated through PKA, calmodulin and RAS SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 7th International Symposium on VIP, PACAP and Related Peptides CY SEP 11-14, 2005 CL Rouen, FRANCE SP Conseil Reg Haute-Normandie, Agglomerat Rouen, Inst Fed Rech Multidisciplinaires Peptides, Inst Natl Sante Rech Med, Municipal Rouen, Sci Act Haute-Normandie, Tech Chime-Biol Sante, Univ Paris 7, Univ Rouen C1 VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol & Hepatol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE VA UCLA Digest Dis Res Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 15 PY 2005 VL 130 IS 3 BP 168 EP 168 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 959OL UT WOS:000231527400096 ER PT J AU Katsel, P Davis, KL Gorman, JM Haroutunian, V AF Katsel, P Davis, KL Gorman, JM Haroutunian, V TI Variations in differential gene expression patterns across multiple brain regions in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; postmortem; gene expression; microarray; brain regions; hippocampus; cingulate cortex; temporal cortex; hippocampus ID CEREBRAL BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; HIPPOCAMPAL-FORMATION; ELDERLY-PATIENTS; AUDITORY HALLUCINATIONS; MICROARRAY ANALYSIS; NEURONAL DENSITY; BIPOLAR DISORDER; WORKING-MEMORY AB Large-scale gene expression studies in schizophrenia (SZ) have generally focused on the dorsolateral prefrontal cortex. Despite a wealth of evidence implicating multiple other brain regions in the disease, studies of other brain regions have been less frequent and have rarely been performed in the same subjects. We analyzed postmortem gene expression in the frontal, cingulate, temporal, parietal and occipital cortices (Brodmann areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7 and 17, respectively) as well as in the hippocampus, caudate nucleus and putamen of persons with schizophrenia and control subjects (N's = 13) using Affymetrix GeneChip (R) microarrays. Under identical data filtering conditions, the superior temporal cortex (BA22) of schizophrenia subjects showed the maximal number of altered transcripts (similar to 1200) compared to controls. Anterior and posterior cingulate cortices (BA23/31, 24/32) and the hippocampus followed the superior temporal cortex with two-times lower numbers of altered transcripts. The dorsolateral prefrontal cortex (BA46), a frequent target of SZ-associated studies, showed substantially fewer altered transcripts (similar to 33). These regional differences in differentially expressed genes could not be accounted for by factors such as total numbers of genes expressed or the filtering conditions and criteria used for identification of differentially expressed genes. These findings suggest that the temporal and cingulate cortices and the hippocampal formation represent brain regions of particular abnormality in SZ and may be more susceptible to the disease process(es) than other regions thus far studied. (c) 2005 Elsevier B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, Room 4F-33A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu NR 98 TC 90 Z9 90 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 SEP 15 PY 2005 VL 77 IS 2-3 BP 241 EP 252 DI 10.1016/j.schres.2005.03.020 PG 12 WC Psychiatry SC Psychiatry GA 962RE UT WOS:000231749100012 PM 15923110 ER PT J AU Brekke, JS Nakagami, E Kee, KS Green, MF AF Brekke, JS Nakagami, E Kee, KS Green, MF TI Cross-ethnic differences in perception of emotion in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE culture; ethnicity; perception of emotion; neurocognition; schizophrenia ID JAPANESE CULTURAL-DIFFERENCES; GENERALIZED POOR PERFORMANCE; UNIVERSAL FACIAL EXPRESSIONS; AFFECT RECOGNITION; SUBJECTIVE EXPERIENCE; SOCIAL COGNITION; MENTAL-HEALTH; DEFICIT; FACE; JUDGMENTS AB Background: The purpose of this study was to examine cross-ethnic differences in Perception of Emotion (POE) in schizophrenia. POE is an emerging construct in schizophrenia and involves the recognition and accurate identification of emotion in the facial and vocal expression of others. It has been implicated as relevant to instrumental functioning in schizophrenia, as well as a potential core deficit or marker for the disorder. Studies have shown the role of culture in shaping the expression and perception of emotion in non-clinical samples. It was hypothesized that ethnic minorities would have lower POE scores than Caucasians, and that the differences on POE would remain significant after controlling for neurocognition. Method: Individuals, 13 1, diagnosed with schizophrenia or schizoaffective disorder participated in the study. There were 59 Euro-American Caucasian, 56 were African-American, and 16 were Latino. Neurocognition was measured as a standardized sum of five neuropsychological measures. Perception of Emotion was measured with facial and voice recognition tasks. Results: Both Latinos and African-Americans scored lower on POE than Caucasians. The cross-ethnic differences on POE remained significant after controlling for neurocognition and overall symptom level. Post hoc analyses showed some support for the predictive validity of the POE measure across cultural contexts. Conclusions: These results suggest that POE in schizophrenia is influenced by ethnicity, and that the ethno-cultural mechanisms influencing POE transcend the shared variation of POE and neurocognition. These results have implications for theories of cross-cultural emotion recognition, measurement bias in POE research, and for the place of culture in the study of POE in schizophrenia. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Brekke, JS (reprint author), Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. EM brekke@usc.edu FU NIMH NIH HHS [MH01628, MH53282] NR 74 TC 17 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP 15 PY 2005 VL 77 IS 2-3 BP 289 EP 298 DI 10.1016/j.schres.2005.04.004 PG 10 WC Psychiatry SC Psychiatry GA 962RE UT WOS:000231749100017 PM 15923111 ER PT J AU Sabatine, MS Cannon, CP Gibson, CM Lopez-Sendon, JL Montalescot, G Theroux, P Lewis, BS Murphy, SA McCabe, CH Braunwald, E AF Sabatine, MS Cannon, CP Gibson, CM Lopez-Sendon, JL Montalescot, G Theroux, P Lewis, BS Murphy, SA McCabe, CH Braunwald, E CA CLARITY TIMI 28 Investigators TI Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics - The PCI-CLARITY study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GLYCOPROTEIN IIB/IIIA INHIBITORS; ANTIPLATELET THERAPY; UNSTABLE ANGINA; PLASMINOGEN-ACTIVATOR; PLATELET ACTIVATION; ENDOTHELIAL-CELLS; ASPIRIN; TRIAL; EVENTS; THROMBOLYSIS AB Context The benefit of clopidogrel pretreatment before percutaneous coronary intervention (PCI) remains debated and its use has not been universally adopted. Objective To determine if clopidogrel pretreatment before PCI in patients with recent ST-segment elevation myocardial infarction (STEMI) is superior to clopidogrel treatment initiated at the time of PCI in preventing major adverse cardiovascular events. Design, Setting, and Participants The PCI-Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) study was a prospectively planned analysis of the 1863 patients undergoing PCI after mandated angiography in CLARITY-Thrombolysis in Myocardial Infarction (TIMI) 28, a randomized, double-blind, placebo-control led trial of clopidogrel in patients receiving fibrinolytics for STEMI. Patients were enrolled at 319 sites in 23 countries from February 2003 through October 2004. Interventions Patients received aspirin and were randomized to receive either clopidogrel (300 mg loading dose, then 75 mg once daily) or placebo initiated with fibrinolysis and given until coronary angiography, which was performed 2 to 8 days after initiation of the study drug. For patients undergoing coronary artery stenting, it was recommended that open-label clopidogrel (including a loading dose) be administered after the diagnostic angiogram. Main Outcome Measures The primary outcome was the incidence of the composite of cardiovascular death, recurrent MI, or stroke from PCI to 30 days after randomization. Secondary outcomes included MI or stroke before PCI and the aforementioned composite from randomization to 30 days. Results Pretreatment with clopidogrel significantly reduced the incidence of cardiovascular death, MI, or stroke following PCI (34 [3.6%] vs 58 [6.2%]; adjusted odds ratio [OR], 0.54 [95% CI, 0.35-0.85]; P = .008). Pretreatment with clopidogrel also reduced the incidence of MI or stroke prior to PCI (37 [4.0%] vs 58 [6.2%]; OR, 0.62 [95% CI, 0.40-0.95]; P = .03). Overall, pretreatment with clopidogrel resulted in a highly significant reduction in cardiovascular death, MI, or stroke from randomization through 30 days (70 [7.5%] vs 112 [12.0%]; adjusted OR, 0.59 [95% CI, 0.43-0.81]; P = .001; number needed to treat=23). There was no significant excess in the rates of TIMI major or minor bleeding (18 [2.0%] vs 17 [1.9%]; P>.99). Conclusions Clopidogrel pretreatment significantly reduces the incidence of cardiovascular death or ischemic complications both before and after PCI and without a significant increase in major or minor bleeding. These data add further support to the early use of clopidogrel in STEMI and the strategy of routine clopidogrel pretreatment in patients undergoing PCI. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Univ La Paz, Dept Cardiol, Madrid, Spain. Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. Montreal Heart Inst, Dept Med, Montreal, PQ H1T 1C8, Canada. Lady Davies Carmel Med Ctr, Dept Cardiovasc Med, Haifa, Israel. Ruth & Bruce Rappaport Sch Med, Haifa, Israel. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU NHLBI NIH HHS [R01 HL072879] NR 46 TC 435 Z9 452 U1 1 U2 3 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 SEP 14 PY 2005 VL 294 IS 10 BP 1224 EP 1232 DI 10.1001/jama.294.10.1224 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 963UI UT WOS:000231831200019 PM 16143698 ER PT J AU Zietman, AL DeSilvio, ML Slater, JD Rossi, CJ Miller, DW Adams, JA Shipley, WU AF Zietman, AL DeSilvio, ML Slater, JD Rossi, CJ Miller, DW Adams, JA Shipley, WU TI Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EXTERNAL-BEAM RADIOTHERAPY; RADICAL PROSTATECTOMY; ANTIGEN LEVELS; CANCER; IRRADIATION; CARCINOMA; GY; ESCALATION; GUIDELINES; BIOPSY AB Context Clinically localized prostate cancer is very prevalent among US men, but recurrence after treatment with conventional radiation therapy is common. Objective To evaluate the hypothesis that increasing the radiation dose delivered to men with clinically localized prostate cancer improves disease outcome. Design, Setting, and Patients Randomized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen (PSA) levels less than 15 ng/mL randomized between January 1996 and December 1999 and treated at 2 US academic institutions. Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 (range, 1.2-8.2) years. Intervention Patients were randomized to receive external beam radiation to a total dose of either 70.2 Gy (conventional dose) or 79.2 Gy (high dose). This was delivered using a combination of conformal photon and proton beams. Main Outcome Measure Increasing PSA level (ie, biochemical failure) 5 years after treatment. Results The proportions of men free from biochemical failure at 5 years were 61.4% (95% confidence interval, 54.6%-68.3%) for conventional-dose and 80.4% (95% confidence interval, 74.7%-86.1%) for high-dose therapy (P<.001), a 49% reduction in the risk of failure. The advantage to high-dose therapy was observed in both the low-risk and the higher-risk subgroups (risk reduction, 51% [P<.001] and 44% [P=.03], respectively). There has been no significant difference in overall survival rates between the treatment groups. Only 1% of patients receiving conventional-dose and 2% receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2% and 1%, respectively, have experienced late morbidity of RTOG grade 3 or greater. Conclusions Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Loma Linda Univ, Med Ctr, Loma Linda, CA USA. Amer Coll Radiol, Philadelphia, PA USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM azietman@partners.org FU NCI NIH HHS [P01 CA21239] NR 27 TC 724 Z9 735 U1 5 U2 25 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 SEP 14 PY 2005 VL 294 IS 10 BP 1233 EP 1239 DI 10.1001/jama.294.10.1233 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 963UI UT WOS:000231831200020 PM 16160131 ER PT J AU Wang, TJ Vasan, RS AF Wang, TJ Vasan, RS TI Epidemiology of uncontrolled hypertension in the United States SO CIRCULATION LA English DT Review ID BLOOD-PRESSURE CONTROL; NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; DISEASE RISK-FACTORS; 3RD NATIONAL-HEALTH; SURVEY NHANES-III; URBAN BLACK-MEN; PRIMARY-CARE; FOLLOW-UP; CARDIOVASCULAR-DISEASE C1 Framingham Heart Dis Epidemiol Study, Newark, NJ 07102 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Sect Prevent Med, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Newark, NJ 07102 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K23 HL-074077, K24-HL-04334, N01-HC-25195] NR 126 TC 149 Z9 154 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 13 PY 2005 VL 112 IS 11 BP 1651 EP 1662 DI 10.1161/CIRCULATIONAHA.104.490599 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 963RG UT WOS:000231821200020 PM 16157784 ER PT J AU Zabetian, CP Samii, A Mosley, AD Roberts, JW Leis, BC Yearout, D Raskind, WH Griffith, A AF Zabetian, CP Samii, A Mosley, AD Roberts, JW Leis, BC Yearout, D Raskind, WH Griffith, A TI A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations SO NEUROLOGY LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM AB Referral-based studies indicate that a mutation (G2019S) in exon 41 of the LRRK2 gene might be a common cause of Parkinson disease (PD). The authors sequenced leucine-rich repeat kinase 2 (LRRK2) exons 31, 35, and 41 in 371 consecutively recruited patients with PD and found mutations in six (1.6%) subjects, including two heterozygous for new putative pathogenic variants (R1441H, IVS31 + 3A -> G). These data confirm the important contribution of LRRK2 to PD susceptibility in a clinic-based population. C1 VA Puget Sound Hlth Care Syst, Geriat Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, NW Parkinsons Dis Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. Virginia Mason Med Ctr, Seattle, WA USA. Evergreen Hosp, Med Ctr, Kirkland, WA USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Geriat Res Educ & Clin Ctr, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306 FU NINDS NIH HHS [K08-NS44138] NR 10 TC 111 Z9 116 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 13 PY 2005 VL 65 IS 5 BP 741 EP 744 DI 10.1212/01.WNL.0000172630.22804.73 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 963RH UT WOS:000231821300016 PM 16157909 ER PT J AU Rosas, HD Hevelone, ND Zaleta, AK Greve, DN Salat, DH Fischl, B AF Rosas, HD Hevelone, ND Zaleta, AK Greve, DN Salat, DH Fischl, B TI Regional cortical thinning in preclinical Huntington disease and its relationship to cognition SO NEUROLOGY LA English DT Article ID NEURONS; BRAIN AB The authors studied presymptomatic individuals with the Huntington disease (HD) mutation to determine whether cortical thinning was present. They found thinning that was regionally selective, semi-independent of striatal volume loss, and correlated with cognitive performance. Early, extensive cortical involvement occurs during the preclinical stages of HD. C1 Harvard Univ, Sch Med, Ctr Neuroimaging Aging & Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Athinoula A Martinos Ctr Biomed Imainging, Charlestown, MA USA. RP Rosas, HD (reprint author), Harvard Univ, Sch Med, Ctr Neuroimaging Aging & Neurodegenerat Dis, 149 13th St Room 2273, Charlestown, MA 02129 USA. EM rosas@helix.mgh.harvard.edu OI Hevelone, Nathanael/0000-0003-4740-2085 FU NCRR NIH HHS [P41-RR14075, R01 RR16594-01A1]; NINDS NIH HHS [NS042861] NR 9 TC 172 Z9 173 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 13 PY 2005 VL 65 IS 5 BP 745 EP 747 DI 10.1212/01.wnl.0000174432.87383.87 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 963RH UT WOS:000231821300017 PM 16157910 ER PT J AU Sun, YL Jiang, XF Chen, SJ Fernandes, N Price, BD AF Sun, YL Jiang, XF Chen, SJ Fernandes, N Price, BD TI A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FATC domain; TRRAP; NuA4; chromatin remodeling ID DOUBLE-STRAND BREAKS; PIK-RELATED KINASES; DNA-DAMAGE; COMPLEX; DOMAIN; PROTEIN; REPAIR; SITES; PHOSPHORYLATION; RECRUITMENT AB The ataxia telangiectasia mutant (ATM) protein kinase regulates the cell's response to DNA damage through the phosphorylation of proteins involved in cell-cycle checkpoints and DNA repair. However, the signal-transduction pathway linking DNA strand breaks to activation of ATM's kinase activity is not clearly defined. Here, we demonstrate that DNA damage induces the rapid acetylation of ATM. This acetylation depends on the Tip60 histone acetyltransferase (HAT). Suppression of Tip60 blocks the activation of ATM's kinase activity and prevents the ATM-dependent phosphorylation of p53 and chk2. Further, inactivation of Tip60 sensitizes cells to ionizing radiation. ATM forms a stable complex with Tip60 through the conserved FATC domain of ATM. The interaction between ATM and Tip60 is not regulated in response to DNA damage. Instead, the HAT activity of the ATM-Tip60 complex is specifically activated by DNA damage. Furthermore, this activation of Tip60 by DNA damage and the recruitment of the ATM-Tip60 complex to sites of DNA damage is independent of ATM's kinase activity.. The results demonstrate that the Tip60 HAT plays a key role in the activation of ATM's kinase activity in response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Price, BD (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, JF223,44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu NR 34 TC 343 Z9 354 U1 2 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 2005 VL 102 IS 37 BP 13182 EP 13187 DI 10.1073/pnas.0504211102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964YG UT WOS:000231916300033 PM 16141325 ER PT J AU Shepard, JL Amatruda, JF Stern, HM Subramanian, A Finkelstein, D Ziai, J Finley, KR Pfaff, KL Hersey, C Zhou, Y Barut, B Freedman, M Lee, C Spitsbergen, J Neuberg, D Weber, G Golub, TR Glickman, JN Kutok, JL Aster, JC Zon, LI AF Shepard, JL Amatruda, JF Stern, HM Subramanian, A Finkelstein, D Ziai, J Finley, KR Pfaff, KL Hersey, C Zhou, Y Barut, B Freedman, M Lee, C Spitsbergen, J Neuberg, D Weber, G Golub, TR Glickman, JN Kutok, JL Aster, JC Zon, LI TI Zebrafish bmyb mutation causes genome instability and increased cancer susceptibility SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell cycle ID CYCLIN-B EXPRESSION; DROSOPHILA-MYB; CELL-CYCLE; GENE-EXPRESSION; C-MYB; TRANSCRIPTION; PROLIFERATION; REPLICATION; PROGRESSION; PLATYFISH AB A major goal of cancer research has been to identify genes that contribute to cancer formation. The similar pathology between zebrafish and human tumors, as well as the past success of large-scale genetic screens in uncovering human disease genes, makes zebrafish an ideal system in which to find such new genes. Here, we show that a zebrafish forward genetic screen uncovered multiple cell proliferation mutants including one mutant, crash&burn (crb), that represents a loss-of-function mutation in bmyb, a transcriptional regulator and member of a putative protooncogene family. crb mutant embryos have defects in mitotic progression and spindle formation, and exhibit genome instability. Regulation of cyclin B levels by bmyb appears to be the mechanism of mitotic accumulation in crb. Carcinogenesis studies reveal increased cancer susceptibility in adult crb heterozygotes. Gene-expression signatures associated with loss of bmyb in zebrafish are also correlated with conserved signatures in human tumor samples, and down-regulation of the B-myb signature genes is associated with retention of p53 function. Our findings show that zebrafish screens can uncover cancer pathways, and demonstrate that loss of function of bmyb is associated with cancer. C1 Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Oregon State Univ, Corvallis, OR 97333 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02215 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. RP Zon, LI (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NHLBI NIH HHS [K08 HL004082, K08 HL04082]; NICHD NIH HHS [1R01 HD044930]; NIDDK NIH HHS [1R01 DK55381, 5K08 DK061849, K08 DK061849, R01 DK055381] NR 37 TC 112 Z9 115 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 2005 VL 102 IS 37 BP 13194 EP 13199 DI 10.1073/pnas.0506583102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964YG UT WOS:000231916300035 PM 16150706 ER PT J AU Kalanithi, PSA Zheng, W Kataoka, Y DiFiglia, M Grantz, H Saper, CB Schwartz, ML Leckman, JF Vaccarino, FM AF Kalanithi, PSA Zheng, W Kataoka, Y DiFiglia, M Grantz, H Saper, CB Schwartz, ML Leckman, JF Vaccarino, FM TI Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GABA; human; postmortem; psychiatry; tic ID EXTERNAL GLOBUS-PALLIDUS; NEOSTRIATAL PROJECTION NEURONS; IMMUNOREACTIVE NEURONS; GABAERGIC INTERNEURONS; IDIOPATHIC DYSTONIA; PAROXYSMAL DYSTONIA; DISORDERS; STRIATUM; MODEL; OSCILLATIONS AB Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterized by motor and vocal tics. Imaging studies found alterations in caudate (Cd) and putamen volumes. To investigate possible alterations in cell populations, postmortem basal ganglia tissue from individuals with TS and normal controls was analyzed by using unbiased stereological techniques. A markedly higher total neuron number was found in the globus pallidus pars interna (GPi) of TS. in contrast, a lower neuron number and density was observed in the globus pallidus pars externa and in the Cd. An increased number and proportion of the GPi neurons were positive for the calcium-binding protein parvalbumin in tissue from TS subjects, whereas lower densities of parvalbumin-positive interneurons were observed in both the Cd and putamen of TS subjects. This change is consistent with a developmental defect in tangential migration of some GABAergic neurons. The imbalance in striatal and GPi inhibitory neuron distribution suggests that the functional dynamics of cortico-striato-thalamic circuitry are fundamentally altered in severe, persistent TS. C1 Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Yale Univ, Dept Neurobiol, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Vaccarino, FM (reprint author), Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. EM flora.vaccarino@yale.edu RI Kalanithi, Paul/B-1074-2012; OI Vaccarino, Flora/0000-0003-2167-981X FU NIMH NIH HHS [P01 MH049351, P01 MH49351] NR 47 TC 229 Z9 235 U1 3 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 2005 VL 102 IS 37 BP 13307 EP 13312 DI 10.1073/pnas.0502624102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964YG UT WOS:000231916300054 PM 16131542 ER PT J AU Kurth, T Hennekens, CH Sturmer, T Sesso, HD Glynn, RJ Buring, JE Gaziano, JM AF Kurth, T Hennekens, CH Sturmer, T Sesso, HD Glynn, RJ Buring, JE Gaziano, JM TI Analgesic use and risk of subsequent hypertension in apparently healthy men SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BLOOD-PRESSURE; ANTIHYPERTENSIVE TREATMENT; PROSTAGLANDIN SYNTHESIS; CARDIOVASCULAR-DISEASE; ACETYLSALICYLIC-ACID; PHYSICIANS HEALTH; RENAL-FUNCTION; BETA-CAROTENE; INHIBITION AB Background: Prospective studies have suggested that women who self-select for use of analgesics have an increased risk of hypertension, but data in men are sparse. We tested whether apparently healthy male physicians who reported analgesic use had an increased risk of subsequent hypertension. Methods: Prospective cohort study of 8229 participants in the Physicians' Health Study who were free of hypertension and completed detailed analgesic questionnaires. Hypertension was defined as self-reported blood pressure of 140/90 mm Hg or higher or use of antihypertensive medication. Results: After a mean of 5.8 years' follow-up, 2234 men (27.2%) reported subsequent hypertension. We categorized the cumulative analgesic use in quintiles. After adjusting for potential confounders, men in the highest quintile had no statistically significant increased risk of hypertension (hazard ratio, 1.12; 95% confidence interval, 0.97-1.31) when compared with those in the lowest quintile. In subgroup analyses, we evaluated the cumulative use of nonsteroidal anti-inflammatory drugs, acetaminophen, and aspirin. Compared with never users, men who reported consuming at least 2500 pills had hazard ratios of 1.05 (95% confidence interval, 0.89-1.24) for nonsteroidal anti-inflammatory drugs, 1.08 (95% confidence interval, 0.87-1.34) for acetaminophen, and 1.16 (95% confidence interval, 0.92-1.48) for aspirin. The results were similar for analgesic use in the year preceding the analgesic questionnaire. Conclusion: In this large cohort, apparently healthy male physicians who self-selected for analgesic use had no significantly increased risk of subsequent hypertension, although a small to moderately increased risk cannot be excluded in observational studies. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Massachusetts Vet Epidemiol Res Ctr, Boston VA Healthcare Syst, Boston, MA USA. Univ Miami, Sch Med, Dept Med, Miami, FL 33152 USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33152 USA. Florida Atlantic Univ, Ctr Excellence, Dept Biomed Sci, Boca Raton, FL 33431 USA. RP Kurth, T (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA 34944, CA 40360, R01 CA097193]; NHLBI NIH HHS [HL 26490, HL 34595] NR 36 TC 23 Z9 25 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 12 PY 2005 VL 165 IS 16 BP 1903 EP 1909 DI 10.1001/archinte.165.16.1903 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 963VS UT WOS:000231834900014 PM 16157836 ER PT J AU Costa, FF AF Costa, FF TI Non-coding RNAs: new players in eukaryotic biology SO GENE LA English DT Review DE non-coding RNAs; RNome; transcriptome analysis; eukaryotes and complex diseases ID PROSTATE-SPECIFIC GENE; NEURAL BC1 RNA; BECKWITH-WIEDEMANN-SYNDROME; PRION PROTEIN CONVERSION; VIRUS-INDUCED LYMPHOMAS; H19 GENE; MESSENGER-RNA; X-CHROMOSOME; BC200 RNA; IN-VITRO AB The completion of the human, mouse and other eukaryotic genomes were important scientific milestones, but they were just small steps towards the understanding of eukaryotic biology. Recent transcriptome analysis and different experimental approaches have identified a surprisingly large number of non-coding RNAs (ncRNAs) in eukaryotic cells. ncRNAs comprise microRNAs, anti-sense transcripts and other Transcriptional Units containing a high density of stop codons and lacking any extensive "Open Reading Frame". They have been shown to regulate gene expression by novel mechanisms such as RNA interference, gene co-suppression, gene silencing, imprinting and DNA demethylation. It is becoming clear that these novel RNAs perform critical functions during development and cell differentiation. There is also mounting evidence of their involvement in cancer and neurological diseases. Together, all this information indicates that ncRNAs are emerging as a new class of functional transcripts in eukaryotes. Therefore, great challenges lie in the years ahead: understanding the molecular biology of higher organisms will require revealing all proteins (Proteome), all ncRNAs (RNome) and their interactions (Interactome) in the complex molecular scenario within eukaryotic cells. (C) 2005 Elsevier B.V. All rights reserved. C1 Ludwig Inst Canc Res, Lab Mol Biol & Genom, BR-01509010 Sao Paulo, Brazil. RP Costa, FF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02129 USA. EM fcosta@partners.org NR 100 TC 172 Z9 191 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 12 PY 2005 VL 357 IS 2 BP 83 EP 94 DI 10.1016/j.gene.2005.06.019 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 969QK UT WOS:000232249400001 PM 16111837 ER PT J AU Gao, M Lewis, G Turner, GM Soubret, A Ntziachristos, V AF Gao, M Lewis, G Turner, GM Soubret, A Ntziachristos, V TI Effects of background fluorescence in fluorescence molecular tomography SO APPLIED OPTICS LA English DT Article ID OPTICAL TOMOGRAPHY; PHOTON MIGRATION; TURBID MEDIA; RECONSTRUCTION; SCATTERING AB Recent advances in optical imaging systems and systemically administered fluorescent probes have significantly improved the ways by which we can visualize proteomics in vivo. A key component in the design of fluorescent probes is a favorable biodistribution, i.e., localization only in the targeted diseased tissue, in order to achieve high contrast and good detection characteristics. In practice, however, there is always some level of background fluorescence present that could result in distorted or obscured visualization and quantification of measured signals. In this study we observe the effects of background fluorescence in tomographic imaging. We demonstrate that increasing levels of background fluorescence result in artifacts when using a linear perturbation algorithm, along with a significant loss of image fidelity and quantification accuracy. To correct for effects of background fluorescence, we have applied cubic polynomial fits to bulk raw measurements obtained from spatially homogeneous and heterogeneous phantoms. We show that subtraction of the average fluorescence response from the raw data before reconstruction can improve image quality and quantification accuracy as shown in relatively homogeneous or heterogeneous phantoms. Subtraction methods thus appear to be a promising route for adaptively correcting nonspecific background fluorochrome distribution. (c) 2005 Optical Society of America. C1 Harvard MIT Div Hlth Sci, Cambridge, MA 02139 USA. Technol Biomed Opt Summer Inst, Cambridge, MA 02139 USA. Princeton Univ, Princeton, NJ 08544 USA. Univ Miami, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Charlestown, MA 02129 USA. RP Harvard MIT Div Hlth Sci, 77 Massachusetts Ave,E25-519, Cambridge, MA 02139 USA. EM vasilis@helix.mgh.harvard.edu FU NIBIB NIH HHS [R01 EB 000750-1] NR 17 TC 40 Z9 40 U1 0 U2 2 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 SEP 10 PY 2005 VL 44 IS 26 BP 5468 EP 5474 DI 10.1364/AO.44.005468 PG 7 WC Optics SC Optics GA 963GG UT WOS:000231791300016 PM 16161661 ER PT J AU Armstrong, SA Look, AT AF Armstrong, SA Look, AT TI Molecular genetics of acute lymphoblastic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID T-CELL LEUKEMIA; LOOP-HELIX PROTEINS; ACUTE LYMPHOCYTIC-LEUKEMIA; FETAL LIVER HEMATOPOIESIS; PEDIATRIC-ONCOLOGY-GROUP; ACUTE MYELOID-LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; DNA-BINDING; PHILADELPHIA-CHROMOSOME; TRANSGENIC MICE AB From its beginnings two decades ago with the analysis of chromosomal translocation breakpoints, research into the molecular pathogenesis of acute lymphoblastic leukemia (ALL) has now progressed to the large-scale resequencing of candidate oncogenes and tumor suppressor genes in the genomes of ALL cases blocked at various developmental stages within the B- and T-cell lineages. In this review, we summarize the findings of these investigations and highlight how this information is being integrated into multistep mutagenesis cascades that impact specific signal transduction pathways and synergistically lead to leukemic transformation. Because of these advances, fueled by improved technology for mutational analysis and the development of small-molecule drugs and monoclonal antibodies, the future is bright for a new generation of targeted therapies. Best illustrated by the successful introduction of imatinib mesylate, these new treatments will interfere with disordered molecular pathways specific for the leukemic cells, and thus should exhibit much less toxicity and fewer long-term adverse effects than currently available therapeutic modalities. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol,Karp Res Labs, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol,Karp Res Labs, Rm 08211,1 Blackfan Circle, Boston, MA 02115 USA. EM Scott.Armstrong@childrens.harvard.edu NR 126 TC 188 Z9 202 U1 7 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2005 VL 23 IS 26 BP 6306 EP 6315 DI 10.1200/JCO.2005.05.047 PG 10 WC Oncology SC Oncology GA 965GJ UT WOS:000231938300004 PM 16155013 ER PT J AU Hideshima, T Chauhan, D Richardson, P Anderson, KC AF Hideshima, T Chauhan, D Richardson, P Anderson, KC TI Identification and validation of novel therapeutic targets for multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PROTEASOME INHIBITOR PS-341; OVERCOMES DRUG-RESISTANCE; BONE-MARROW MICROENVIRONMENT; DONOR LYMPHOCYTE INFUSION; HISTONE DEACETYLASE INHIBITION; STEM-CELL TRANSPLANTATION; GROWTH-FACTOR SECRETION; NECROSIS-FACTOR-ALPHA; MALIGNANT B-CELLS; IN-VIVO MODEL AB In vitro and in vivo models have been developed that have allowed for delineation of mechanisms of multiple myeloma (MM) cell homing to bone marrow (BM); tumor cell adhesion to extracellular matrix proteins and BM stromal cells; and cytokine-mediated growth, survival, drug resistance, and migration within the BM milieu. Delineation of the signaling cascades mediating these sequelae has identified multiple novel therapeutic targets in the tumor cell and its BM microenvironment. Importantly, novel therapies targeting the tumor cell and the BM, as well as those targeting the tumor cell or BM alone, can overcome the growth, survival, conventional drug resistance, and migration of MM cells bound to BM using both in vitro and in vivo severe combined immunodeficiency mouse models of human MM. These studies have translated rapidly from the bench to the bedside in derived clinical trials, and have already led to the United States Food and Drug Administration approval of the novel proteasome inhibitor bortezomib for treatment of relapsed/refractory MM. Novel agents will need to be combined to enhance cytotoxicity, avoid development of drug resistance, and allow for use of lower doses in combination therapies. Genomics, proteomics, and cell signaling studies have helped to identify in vivo mechanisms of sensitivity versus resistance to novel therapies, as well as aiding in the rational application of combination therapies. These studies have therefore provided the framework for a new treatment paradigm targeting the VIM cell in its BM milieu to overcome drug resistance and improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA10070-01, R0-1 CA 50947]; PHS HHS [P0-1 78378] NR 97 TC 59 Z9 59 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2005 VL 23 IS 26 BP 6345 EP 6350 DI 10.1200/JCO.2005.05.024 PG 6 WC Oncology SC Oncology GA 965GJ UT WOS:000231938300009 PM 16155018 ER PT J AU Wagers, AJ Conboy, IM AF Wagers, AJ Conboy, IM TI Cellular and molecular signatures of muscle regeneration: Current concepts and controversies in adult myogenesis SO CELL LA English DT Review ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW TRANSPLANTATION; GROWTH-FACTOR-I; SKELETAL-MUSCLE; SATELLITE CELLS; MUSCULAR-DYSTROPHY; SELF-RENEWAL; PROGENITOR CELLS; PRECURSOR CELLS; CLONAL ANALYSIS AB Adult skeletal muscle generates force in a controlled and directed manner through the contraction of highly specialized, postmitotic, multinucleated myofibers. Lifelong muscle function relies on maintenance and regeneration of myofibers through a highly regulated process beginning with activation of normally quiescent muscle precursor cells and proceeding with formation of proliferating progenitors that fuse to generate differentiated myofibers. In this review, we describe the historical basis and current evidence for the identification of satellite cells as adult muscle stem cells, critically evaluate contributions of other cells to adult myogenesis, and summarize existing data regarding the origins, genetic markers, and molecular regulation of satellite cells in normal, diseased, and aged muscle. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94702 USA. RP Wagers, AJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. EM amywagers@joslin.harvard.edu; iconboy@berkeley.edu FU NIA NIH HHS [K01-AG25652]; Wellcome Trust NR 105 TC 247 Z9 262 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 9 PY 2005 VL 122 IS 5 BP 659 EP 667 DI 10.1016/j.cell.2005.08.021 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 963ZC UT WOS:000231844300007 PM 16143100 ER PT J AU Wedig, MM Rauch, SL Albert, MS Wright, CI AF Wedig, MM Rauch, SL Albert, MS Wright, CI TI Differential amygdala habituation to neutral faces in young and elderly adults SO NEUROSCIENCE LETTERS LA English DT Article DE magnetic resonance imaging; amygdala; habituation; aging ID AGE-RELATED DIFFERENCES; GALVANIC SKIN-RESPONSE; ALZHEIMERS-DISEASE; FUNCTIONAL MRI; FMRI; STIMULATION; ACTIVATION; FEARFUL AB Habituation is a highly adaptive property of the nervous system, which allows for the allocation of attention and other cognitive resources to more imperative environmental events. The arnygdala is an important site of habituation in humans, but no studies to date have examined the effects of aging on amygdala habituation. Given the amygdala's role in evaluating the salience of a stimulus and initiating behavioral responses, the potential importance of amygdala habituation in aging may be far-reaching. Therefore, we assessed for differences in habituation in the amygdalae of healthy young and elderly adults during repeated presentations of neutral human faces using functional magnetic resonance imaging (fMRI). In addition, we evaluated the relationship between amygdala volume and habituation, to examine the effects of atrophy. Eighteen healthy young controls and 18 healthy elderly subjects were scanned with fMRI during viewing of repeatedly presented neutral human face stimuli. Significant fMRI signal decrement was observed across all subjects for early versus late face presentations. Analysis of group, condition, and hemisphere revealed a significant three-way interaction, with right greater than left habituation in the young, but left greater than right amygdala habituation in the elderly. Volumetric and correlational analyses demonstrated that amygdala volume is associated with habituation in the right, but not left, hemisphere. We conclude that, in healthy elderly adults, the amygdala retains its adaptive habituation response, but speculate that intrinsic changes in amygdala anatomy during aging may modulate its laterality. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gerontol Res Unit, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. RP Wright, CI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, 13th St,Bldg 149,2nd Floor, Charlestown, MA 02129 USA. EM ciwright@partners.org FU NIMH NIH HHS [MH64806] NR 23 TC 32 Z9 32 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 9 PY 2005 VL 385 IS 2 BP 114 EP 119 DI 10.1016/j.neulet.2005.05.039 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 951PP UT WOS:000230943100005 PM 15961229 ER PT J AU Nichols, CM Myckatyn, TM Rickman, SR Fox, IK Hadlock, T Mackinnon, SE AF Nichols, CM Myckatyn, TM Rickman, SR Fox, IK Hadlock, T Mackinnon, SE TI Choosing the correct functional assay: A comprehensive assessment of functional tests in the rat SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE rat; functional test; nerve; forelimb; hind limb; vibrissae; sensory; motor ID PERIPHERAL-NERVE RECONNECTION; WALKING TRACK ANALYSIS; SKILLED FORELIMB MOVEMENTS; ORBICULARIS OCULI MUSCLE; DOPAMINE-DEPLETED RATS; MATRIX REACHING TASK; DORSAL COLUMN LESION; MOTOR CORTEX LESIONS; SCIATIC-NERVE; LIMB USE AB While there are several ways to quantify peripheral nerve regeneration; the true measure of successful outcome is functional recovery. Functional tests are relatively easily conducted in human subjects; however it is more difficult in a laboratory animal. The laboratory rat is an excellent animal model of peripheral nerve injury and has been used extensively in the field of peripheral nerve research. Due to the intense interest in the rat as an experimental model, functional assays have been reported. In an effort to provide a resource to which investigators can refer when considering the most appropriate functional assay for a given experiment, the authors have compiled and tabulated the available functional tests applicable to various models of rat nerve injury. (c) 2005 Elsevier B.V. All rights reserved. C1 Washington Univ, Sch Med, Div Plast & Reconstruct Surg, St Louis, MO 63110 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Mackinnon, SE (reprint author), Washington Univ, Sch Med, Div Plast & Reconstruct Surg, 660 S Euclid Ave,Campus Box 8238, St Louis, MO 63110 USA. EM mackinnons@msnotes.wustl.edu NR 147 TC 58 Z9 58 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP 8 PY 2005 VL 163 IS 2 BP 143 EP 158 DI 10.1016/j.bbr.2005.05.003 PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 961LX UT WOS:000231665000001 PM 15979168 ER PT J AU Johnson, RT Gonzalez, RG Frosch, MP Nguyen, T Harris, NL Ronan, LJ Venna, N Axelrod, L AF Johnson, RT Gonzalez, RG Frosch, MP Nguyen, T Harris, NL Ronan, LJ Venna, N Axelrod, L TI An 80-year-old man with fatigue, unsteady gait, and confusion - Prion disease (sporadic Creutzfeldt-Jakob disease with MM1) PrPSc SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FATAL FAMILIAL INSOMNIA; DIFFUSION-WEIGHTED MRI; BLOOD-TRANSFUSION; VARIANT; PROTEIN; NEUROPATHOLOGY; CLASSIFICATION; PATIENT; SAMPLES C1 Johns Hopkins Univ, Sch Med, Dept Neurol Microbiol & Neurosci, Baltimore, MD 21218 USA. Bloomberg Sch Publ Hlth, Baltimore, MD USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Johnson, RT (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol Microbiol & Neurosci, Baltimore, MD 21218 USA. NR 26 TC 6 Z9 6 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 8 PY 2005 VL 353 IS 10 BP 1042 EP 1050 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 961YQ UT WOS:000231698200011 PM 16148290 ER PT J AU Rosenzweig, A AF Rosenzweig, A TI Circulating endothelial progenitors - Cells as biomarkers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANGIOGENESIS; NEOVASCULARIZATION; MOBILIZATION C1 Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Boston, MA 02114 USA. NR 13 TC 51 Z9 58 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 SEP 8 PY 2005 VL 353 IS 10 BP 1055 EP 1057 DI 10.1056/NEJMe058134 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 961YQ UT WOS:000231698200013 PM 16148292 ER PT J AU Liu, TC Kirn, D AF Liu, TC Kirn, D TI Viruses with deletions in antiapoptotic genes as potential oncolytic agents SO ONCOGENE LA English DT Review DE oncolytic; virus; cancer; apoptosis; virology; gene therapy ID E1B 19-KILODALTON PROTEIN; NECROSIS-FACTOR-ALPHA; APOPTOTIC CELL-DEATH; TYPE-1 US11 PROTEIN; INFLUENZA-A VIRUS; INFECTED-CELLS; DL1520 ONYX-015; HOST-RANGE; IN-VIVO; ADENOVIRUS PROTEINS AB Replication-selective oncolytic viruses have emerged as a new treatment platform for cancers. However, selectivity and potency need to be improved before virotherapy can become a standard treatment modality. In addition, mechanisms that can be incorporated to enable targeting a broad range of cancer types are highly desirable. Cancer cells are well known to have multiple blocks in apoptosis pathways. On the other hand, viruses have evolved to express numerous antiapoptotic genes to antagonize apoptosis induced upon infection. Viruses with deletions in antiapoptotic genes can therefore be complemented by antiapoptotic genetic changes in cancer cells for efficient replication and oncolysis. In this review, we summarize the recent development of this concept, the potential obstacles, and future directions for optimization. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Mol Neurosurg Lab, Boston, MA 02114 USA. Univ Oxford, Dept Clin Pharmacol, Oxford OX1 2JD, England. Jennnerex Biotherapeut Inc, Mountain View, CA USA. RP Liu, TC (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM tachiangliu@yahoo.com; dkirn@jennerex.com NR 90 TC 22 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 8 PY 2005 VL 24 IS 40 BP 6069 EP 6079 DI 10.1038/sj.onc.1208734 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 962GD UT WOS:000231718100001 PM 16155595 ER PT J AU Weissman, JS Betancourt, J Campbell, EG Park, ER Kim, M Clarridge, B Blumenthal, D Lee, KC Maina, AW AF Weissman, JS Betancourt, J Campbell, EG Park, ER Kim, M Clarridge, B Blumenthal, D Lee, KC Maina, AW TI Resident physicians' preparedness to provide cross-cultural care SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIDDEN CURRICULUM; INTERNAL-MEDICINE; MANAGED CARE; COMPETENCE; EDUCATION; SELF; VIEWS; PERSPECTIVES; STRATEGY; FACULTY AB Context Two recent reports from the Institute of Medicine cited cross-cultural training as a mechanism to address racial and ethnic disparities in health care, but little is known about residents' educational experience in this area. Objective To assess residents' attitudes about cross-cultural care, perceptions of their preparedness to deliver quality care to diverse patient populations, and educational experiences and educational climate regarding cross-cultural training. Design, Setting, and Participants A survey was mailed in the winter of 2003 to a stratified random sample of 3435 resident physicians in their final year of training in emergency medicine, family practice, internal medicine, obstetrics/gynecology, pediatrics, psychiatry, or general surgery at US academic health centers. Results Responses were obtained from 2047 (60%) of the sample. Virtually all (96%) of the residents indicated that it was moderately or very important to address cultural issues when providing care. The number of respondents who indicated that they believed they were not prepared to care for diverse cultures in a general sense was only 8%. However, a larger percentage of respondents believed they were not prepared to provide specific components of cross-cultural care, including caring for patients with health beliefs at odds with Western medicine (25%), new immigrants (25%), and patients whose religious beliefs affect treatment (20%). In addition, 24% indicated that they lacked the skills to identify relevant cultural customs that impact medical care. In contrast, only a small percentage of respondents (1%-2%) indicated that they were not prepared to treat clinical conditions or perform procedures common in their specialty. Approximately one third to half of the respondents reported receiving little or no instruction in specific areas of cross-cultural care beyond what was learned in medical school. Forty-one percent (family medicine) to 83% (surgery and obstetrics/ gynecology) of respondents reported receiving little or no evaluation in cross-cultural care during their residencies. Barriers to delivering cross-cultural care included lack of time (58%) and lack of role models (31%). Conclusions Resident physicians' self-reported preparedness to deliver cross-cultural care lags well behind preparedness in other clinical and technical areas. Although cross-cultural care was perceived to be important, there was little clinical time allotted during residency to address cultural issues, and there was little training, formal evaluation, or role modeling. These mixed educational messages indicate the need for significant improvement in cross-cultural education to help eliminate racial and ethnic disparities in health care. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Ewha Womans Univ, Seoul, South Korea. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jweissman@partners.org NR 40 TC 134 Z9 134 U1 0 U2 12 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 SEP 7 PY 2005 VL 294 IS 9 BP 1058 EP 1067 DI 10.1001/jama.294.9.1058 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 960XU UT WOS:000231627300006 PM 16145026 ER PT J AU Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Tu, DS Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Pater, JL AF Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Tu, DS Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Pater, JL TI Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated findings from NCICCTG MA.17 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR; AROMATASE INHIBITORS; CLINICAL-PHARMACOLOGY; AMERICAN-SOCIETY; RECURRENCE; RESISTANCE; ANASTROZOLE; COMBINATION AB Background. Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P=.002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P=.3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P=.04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patients. C1 Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. John Wayne Canc Inst, Santa Monica, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, B-1000 Brussels, Belgium. SAAK IBCSG Operat Off, Bern, Switzerland. Natl Canc Inst canada, Clin Trials Grp, Kingston, ON, Canada. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Washington, Seattle, WA 98195 USA. Johns hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. NCI, Clin Invest Branch, Rockville, MD USA. Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 55 Fruit St,Cox Bldg,Suite 640, Boston, MA 02114 USA. EM pgoss@partners.org OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA21115, CA25224, CA31946, CA32102, CA38926] NR 45 TC 673 Z9 704 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 7 PY 2005 VL 97 IS 17 BP 1262 EP 1271 DI 10.1093/jnci/dji250 PG 10 WC Oncology SC Oncology GA 969YU UT WOS:000232272900012 PM 16145047 ER PT J AU Boverman, G Miller, EL Ang, L Zhang, Q Chaves, T Brooks, DH Boas, DA AF Boverman, G Miller, EL Ang, L Zhang, Q Chaves, T Brooks, DH Boas, DA TI Quantitative spectroscopic diffuse optical tomography of the breast guided by imperfect a ptiori structural information SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID GENERALIZED CROSS-VALIDATION; NEAR-INFRARED SPECTROSCOPY; IMAGE-RECONSTRUCTION; BOUNDARY-CONDITIONS; OXYGEN-SATURATION; IN-VIVO; TISSUE; MAMMOGRAPHY; HEMOGLOBIN; RESOLUTION AB Spectroscopic diffuse optical tomography (DOT) can directly image the concentrations of physiologically significant chromophores in the body. This information may be of importance in characterizing breast tumours and distinguishing them from benign structures. This paper studies the accuracy with which lesions can be characterized given a physiologically realistic situation in which the background architecture of the breast is heterogeneous yet highly structured. Specifically, in simulation studies, we assume that the breast is segmented into distinct glandular and adipose regions. Imaging with a high-resolution imaging modality, such as magnetic resonance imaging, in conjunction with a segmentation by a clinical expert, allows the glandular/adipose boundary to be determined. We then apply a two-step approach in which the background chromophore concentrations of each region are estimated in a nonlinear fashion, and a more localized lesion is subsequently estimated using a linear perturbational approach. In addition, we examine the consequences which errors in the breast segmentation have on estimating both the background and inhomogeneity chromophore concentrations. C1 Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Univ Calif Irvine, Beckman Laser Inst, E Irvine, CA 92612 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Boverman, G (reprint author), Northeastern Univ, Dept Elect & Comp Engn, 302 Stearns Hall, Boston, MA 02115 USA. EM gboverma@ece.neu.edu RI Miller, Eric/B-2546-2008; ANG, Lay Kee/F-8115-2015 OI Miller, Eric/0000-0002-3156-6002; ANG, Lay Kee/0000-0003-2811-1194 NR 46 TC 44 Z9 44 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 7 PY 2005 VL 50 IS 17 BP 3941 EP 3956 DI 10.1088/0031-9155/50/17/002 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 967SV UT WOS:000232112400002 PM 16177522 ER PT J AU Niewoehner, DE Rice, K Cote, C Paulson, D Cooper, JAD Korducki, L Cassino, C Kesten, S AF Niewoehner, DE Rice, K Cote, C Paulson, D Cooper, JAD Korducki, L Cassino, C Kesten, S TI Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator - A Randomized trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COPD; MULTICENTER; MANAGEMENT; THERAPY; SYSTEM; CELLS AB Background: Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and health resource use ramifications. Objective: To prospectively evaluate the effectiveness of a long-acting inhaled anticholinergic bronchodilator, tiotropium, in reducing COPD exacerbations and exacerbation-related health care utilization. Design: Randomized, double-blind study. Setting: 26 Veterans Affairs medical centers. Patients: 1829 patients with moderate to severe COPD (mean baseline FEV1, 36% predicted). Intervention: once-daily tiotropium (18 mu g) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators. Measurements: The coprimary end points were the percentage of patients with a COPD exacerbation and the percentage of patients with a COPD-related hospitalization. Results: Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, -5.7 percentage points [95% CI, -10.4 to -1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, -3.0 percentage points [CI, -5.9 to -0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates. Limitations: Trial participants were enrolled from 1 health care system, and 99% were men. The follow-up period extended for only 6 months. Conclusions: Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD. C1 Vet Adm Med Ctr, Pulm Sect 111N, Minneapolis, MN 55417 USA. Bay Pines Vet Affairs Med Ctr, Bay Pines, FL USA. Hunter Holmes McGuire Vet Affairs Med Ctr, Richmond, VA USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT USA. RP Niewoehner, DE (reprint author), Vet Adm Med Ctr, Pulm Sect 111N, 1 Vet Dr, Minneapolis, MN 55417 USA. EM niewo001@umn.edu NR 25 TC 276 Z9 282 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 6 PY 2005 VL 143 IS 5 BP 317 EP 326 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 961TE UT WOS:000231683900001 PM 16144890 ER PT J AU Kathiresan, S Larson, MG Vasan, RS Guo, CY Vita, JA Mitchell, GF Keyes, MJ Newton-Cheh, C Musone, SL Lochner, AL Drake, JA Levy, D O'Donnell, CJ Hirschhorn, JN Benjamin, EJ AF Kathiresan, S Larson, MG Vasan, RS Guo, CY Vita, JA Mitchell, GF Keyes, MJ Newton-Cheh, C Musone, SL Lochner, AL Drake, JA Levy, D O'Donnell, CJ Hirschhorn, JN Benjamin, EJ TI Common genetic variation at the endothelial nitric oxide synthase locus and relations to brachial artery vasodilator function in the community SO CIRCULATION LA English DT Article DE endothelium; epidemiology; genetics; nitric oxide synthase ID CORONARY-HEART-DISEASE; LINKAGE DISEQUILIBRIUM; MYOCARDIAL-INFARCTION; SHEAR-STRESS; BLOOD-FLOW; ASSOCIATION; DYSFUNCTION; HAPLOTYPES; RISK; POLYMORPHISMS AB Background - Sequence variants at the endothelial nitric oxide synthase (NOS3) locus have been associated with endothelial function measures, but replication has been limited. Methods and Results - In reference pedigrees, we characterized linkage disequilibrium structure at the NOS3 locus using 33 common single nucleotide polymorphisms (SNPs). Eighteen SNPs that capture underlying common variation were genotyped in unrelated Framingham Heart Study participants (49.5% women; mean age, 62 years) with measured brachial artery flow-mediated dilation (n = 1446) or hyperemic flow velocity (n = 1043). Within 3 defined blocks of strong linkage disequilibrium that spanned NOS3, 11 SNPs captured > 80% of common haplotypic variation. Among men, there were nominally significant associations between 8 NOS3 SNPs (minimum P = 0.002) and between haplotypes (minimum P=0.002) and either flow-mediated dilation or hyperemic flow velocity. In women, we did not observe significant associations between NOS3 SNPs or haplotypes and endothelial function measures. To correct for multiple testing, we constructed 1000 bootstrapped null data sets and found that empirical probability values exceeded 0.05 for both phenotypes. Conclusions - A parsimonious set of SNPs captures common genetic variation at the NOS3 locus. A conservative interpretation of our results is that, accounting for multiple testing, we did not observe statistically significant relations between NOS3 sequence variants and endothelial function measures in either sex. The nominal associations of select NOS3 variants with endothelial function in men (unadjusted for multiple testing) should be viewed as hypothesis-generating observations and may merit testing in other cohorts and experimental designs. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Evans Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Cardiovasc Engn Inc, Waltham, MA USA. MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Cardiol, Div Genet, Childrens Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Div Endocrinol, Childrens Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, Dept Med, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL060040, HL070100, HL071039, HL66582, K24HL004334, N01-HC-25195] NR 50 TC 19 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 6 PY 2005 VL 112 IS 10 BP 1419 EP 1427 DI 10.1161/CIRCULATIONHA.105.544619 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 961VC UT WOS:000231688900009 PM 16129794 ER PT J AU Rocha-Singh, K Jaff, MR Rosenfield, K AF Rocha-Singh, K Jaff, MR Rosenfield, K CA ASPIRE 2 Trial Investigators TI Evaluation of the safety and effectiveness of renal artery stenting after unsuccessful balloon angioplasty - The ASPIRE-2 study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RENOVASCULAR DISEASE; SURGICAL-MANAGEMENT; PALMAZ STENT; FOLLOW-UP; STENOSIS; MULTICENTER; PLACEMENT; RISK AB OBJECTIVES This study sought to define the safety and durability of renal stenting after suboptimal/failed renal artery angioplasty in patients with suspected renovascular hypertension. BACKGROUND Few prospective multicenter studies have detailed the safety, efficacy, and long-term clinical benefits of renal artery stent revascularization in hypertensive patients with aorto-ostial atherosclerotic renal artery lesions. METHODS This non-randomized study enrolled 208 patients with de novo or restenotic >= 70% aorto-ostial renal artery stenoses, who underwent implantation of a balloon-expandable stent after unsuccessful percutaneous transluminal renal angioplasty (PTRA), which was defined as a >= 50% residual stenosis, persistent translesional pressure gradient, or a flow-limiting dissection. The primary end point was the nine-month quantitative angiographic or duplex ultrasonography restenosis rate adjudicated by core laboratory analysis. Secondary end points included renal function, blood pressure, and cumulative incidence of major adverse events and target lesion revascularization at 24 months. RESULTS The stent procedure was immediately successful in 182 of 227 (80.2%) lesions treated. The nine-month restenosis rate was 17.4%. Systolic/diastolic blood pressure decreased from 168 +/- 25/82 +/- 13 mm Hg (mean +/- standard deviation) at baseline to 149 +/- 24/77 +/- 12 mm Hg at 9 months (p < 0.001 vs. baseline), and 149 +/- 25/77 +/- 12 mm Hg at 24 months (p < 0.001 vs. baseline). Mean serum creatinine concentration was unchanged from baseline values at 9 and 24 months. The 24-month cumulative rate of major adverse events was 19.7%. CONCLUSIONS In hypertensive patients with aorto-ostial atherosclerotic renal artery stenosis in whom PTRA is unsuccessful, Palmaz (Cordis Corp., Warren, New Jersey) balloon-expandable stents provide a safe and durable revascularization strategy, with a beneficial impact on hypertension. C1 Prairie Heart Inst, Vasc Med Program, Springfield, IL 62794 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rocha-Singh, K (reprint author), Prairie Heart Inst, Vasc Med Program, POB 19420, Springfield, IL 62794 USA. EM ksingh@prairieheart.com NR 25 TC 103 Z9 105 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 6 PY 2005 VL 46 IS 5 BP 776 EP 783 DI 10.1016/j.jacc.2004.11.073 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 961AW UT WOS:000231635300006 PM 16139124 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, RP Braunwald, E TI The year in non-ST-segment elevation acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID C-REACTIVE PROTEIN; TIMI RISK SCORE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; EARLY INVASIVE MANAGEMENT; GLYCOPROTEIN IIB/IIIA BLOCKADE; TRIPLE ANTIPLATELET THERAPY; NATRIURETIC PEPTIDE LEVELS; TISSUE-LEVEL PERFUSION; TO-Z TRIAL C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor Offices, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 140 TC 27 Z9 27 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 SEP 6 PY 2005 VL 46 IS 5 BP 906 EP 919 DI 10.1016/j.jacc.2005.06.051 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 961AW UT WOS:000231635300025 PM 16139143 ER PT J AU Storey, JD Xiao, WZ Leek, JT Tompkins, RG Davis, RW AF Storey, JD Xiao, WZ Leek, JT Tompkins, RG Davis, RW TI Significance analysis of time course microarray experiments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; differential expression; expression arrays; Q values; time series ID GENE-EXPRESSION DATA; HUMAN KIDNEY; DISEASE; PATTERNS; CURVES; MODEL AB Characterizing the genome-wide dynamic regulation of gene expression is important and will be of much interest in the future. However, there is currently no established method for identifying differentially expressed genes in a time course study. Here we propose a significance method for analyzing time course microarray studies that can be applied to the typical types of comparisons and sampling schemes. This method is applied to two studies on humans. In one study, genes are identified that show differential expression over time in response to in vivo endotoxin administration. By using our method, 7,409 genes are called significant at a 1% false-discovery rate level, whereas several existing approaches fail to identify any genes. In another study, 417 genes are identified at a 10% false-discovery rate level that show expression changing with age in the kidney cortex. Here it is also shown that as many as 47% of the genes change with age in a manner more complex than simple exponential growth or decay. The methodology proposed here has been implemented in the freely distributed and open-source EDGE software package. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. Stanford Univ, Dept Biochem, Palo Alto, CA 94304 USA. Shriners Burn Ctr, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Storey, JD (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM jstorey@u.washington.edu; dbowe@stanford.edu RI Storey, John/B-5282-2011; OI xiao, wenzhong/0000-0003-4944-6380 FU NHGRI NIH HHS [R01 HG002913, R01 HG002913-01]; NIGMS NIH HHS [U54 GM062119, U54 GM2119-03] NR 30 TC 323 Z9 327 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 6 PY 2005 VL 102 IS 36 BP 12837 EP 12842 DI 10.1073/pnas.0504609102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 962FP UT WOS:000231716700036 PM 16141318 ER PT J AU Braunwald, E Gotto, AM AF Braunwald, E Gotto, AM TI Time to benefit in lipid-lowering trials - Introduction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CORONARY; CHOLESTEROL C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Cornell Univ, Joan & Sanford I Weill Med Coll, New York, NY USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 4 TC 0 Z9 0 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 SEP 5 PY 2005 VL 96 IS 5A SU S BP 1F EP 2F DI 10.1016/j.amjcard.2005.06.020 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 962PR UT WOS:000231745200001 ER PT J AU Petryshen, TL Kirby, A Rockwell, GN Waggoner, SG O'Leary, SB Aldinger, KA Daly, MJ Sklar, P AF Petryshen, TL Kirby, A Rockwell, GN Waggoner, SG O'Leary, SB Aldinger, KA Daly, MJ Sklar, P TI Identification of genes involved in prepulse inhibition of startle, an endophenotype of schizophrenia, in mouse chromosome substitution strains SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA USA. EM tracey@broad.mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 8 EP 8 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300020 ER PT J AU Sklar, P Perlis, RH Fagerness, J Smoller, JW Pato, MT Pato, CN Purcell, S AF Sklar, P Perlis, RH Fagerness, J Smoller, JW Pato, MT Pato, CN Purcell, S TI Identification of epistatic interactions in two examples: Myelin related genes in bipolar disorder and GABA(A) receptor subunit genes in schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. VAMC, Washington, DC USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. Georgetown Univ, Dept Psychiat, Washington, DC 20057 USA. EM sklar@psych.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 8 EP 9 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300022 ER PT J AU Lasky-Su, JA Lange, C Laird, N Tsuang, MT Faraone, SV Sklar, P AF Lasky-Su, JA Lange, C Laird, N Tsuang, MT Faraone, SV Sklar, P TI Family based association analysis of a statistically derived quantitative trait for ADHD reveals an association in DRD4 with inattentive symptoms in ADHD individuals SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. SUNY Upstate Med Univ, Syracuse, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jsu@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 9 EP 9 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300025 ER PT J AU Santangelo, SL Papandonatos, GD McCaffery, JM Lyons, M Purcell, S Tsuang, MT Niaura, R Buka, S AF Santangelo, SL Papandonatos, GD McCaffery, JM Lyons, M Purcell, S Tsuang, MT Niaura, R Buka, S TI Association of the serotonin transporter gene with nicotine dependence SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Brown Med Sch, Dept Community Hlth, Ctr Stat Sci, Providence, RI USA. Brown Med Sch, Dept Psychiat & Human Behav, Ctr Behav Med, Providence, RI USA. Brown Med Sch, Dept Psychiat & Human Behav, Ctr Prevent Med, Providence, RI USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Univ Calif San Diego, Inst Behav Genom, San Diego, CA 92103 USA. Ctr Transdisciplinary Res, Dept Psychiat & Human Behav, Providence, RI USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. EM ssantang@psych.mgh.harvard.edu RI Lyons, Michael/B-6119-2011; Buka, Stephen/H-7335-2014; Papandonatos, George/J-2328-2014 OI Buka, Stephen/0000-0002-8578-9308; NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 16 EP 17 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300053 ER PT J AU Seidman, LJ Thermenos, HW Poldrack, RA Peace, NK Koch, JK Faraone, SV Tsuang, MT AF Seidman, LJ Thermenos, HW Poldrack, RA Peace, NK Koch, JK Faraone, SV Tsuang, MT TI Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: An FMRI study of working memory SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury VA Med Ctr, Cambridge, MA 02140 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, MIT, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90095 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, SUNY Genet Res Program, Syracuse, NY 13210 USA. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, La Jolla, CA 92093 USA. EM larry_seidman@hms.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 18 EP 19 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300059 ER PT J AU Petryshen, TL Sabeti, PC Aldinger, KA Tahl, AR Frye, B Waggoner, SG Lim, Y Daly, MJ McInnis, MG DePaulo, RJ Smoller, JW Pulver, AE Sklar, P AF Petryshen, TL Sabeti, PC Aldinger, KA Tahl, AR Frye, B Waggoner, SG Lim, Y Daly, MJ McInnis, MG DePaulo, RJ Smoller, JW Pulver, AE Sklar, P TI Further investigation of association between bipolar disorder and BDNF: Characterization of population genetic structure and haplotype association studies in four patient samples SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp,Sch Med, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. EM tracey@broad.mit.edu RI McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 28 EP 28 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300094 ER PT J AU Cusin, C Perlis, RH Fagerness, J Yamaki, L Sklar, P Fava, M Smoller, JM AF Cusin, C Perlis, RH Fagerness, J Yamaki, L Sklar, P Fava, M Smoller, JM TI Association between tryptophan hydroxylase 2 polymorphisms and major depressive disorder in women SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. EM ccusin@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 31 EP 31 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300102 ER PT J AU Kim, J Biederman, J Arbeitman, L Fagerness, J Doyle, A Petty, C Perlis, R Purcell, S Smoller, J Sklar, P Faraone, SV AF Kim, J Biederman, J Arbeitman, L Fagerness, J Doyle, A Petty, C Perlis, R Purcell, S Smoller, J Sklar, P Faraone, SV TI Association between SNAP-25 with ADHD with comorbid major depressive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Pediat Psychopharmacol Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Cambridge, MA 02138 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. EM jwkim@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 57 EP 57 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300201 ER PT J AU Lasky-Su, J Lange, C Laird, N Tsuang, M Faraone, S Sklar, P AF Lasky-Su, J Lange, C Laird, N Tsuang, M Faraone, S Sklar, P TI A study of how socioeconomic status moderates the relationship between SNPS encompassing BDNF and ADHD symptom counts in ADHD families SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Calif San Diego, San Diego, CA 92103 USA. SUNY Upstate Med Univ, Syracuse, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jsu@hsph.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 57 EP 58 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300202 ER PT J AU Mick, E Wozniak, J Wilens, T Biederman, J Faraone, S AF Mick, E Wozniak, J Wilens, T Biederman, J Faraone, S TI Association of DRD4 exon III polymorphism with familial risk of ADHD in children with bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. SUNY Syracuse, Med Genet Res Ctr, Syracuse, NY USA. SUNY Syracuse, Dept Psychiat, Syracuse, NY USA. EM mick@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 59 EP 59 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300208 ER PT J AU Stewart, S Illmann, C Geller, DA Leckman, JF King, R Pauls, DL AF Stewart, S Illmann, C Geller, DA Leckman, JF King, R Pauls, DL TI Controlled family study of ADHD and Tourette's disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen ID ATTENTION-DEFICIT DISORDER C1 Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. EM estewartl@partners.org OI Stewart, S. Evelyn/0000-0002-0994-6383 NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 62 EP 62 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300219 ER PT J AU Fan, J Sklar, P AF Fan, J Sklar, P TI Meta-analysis reveals association between tryptophan hydroxylase gene (TPH1) A218C polymorphism and bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. EM jinbo@broad.mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 77 EP 77 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300274 ER PT J AU Haggarty, SJ Fass, DM Shnider, S Murthy, VN Bragg, D Breakefield, XO Sklar, P Scolnick, EM AF Haggarty, SJ Fass, DM Shnider, S Murthy, VN Bragg, D Breakefield, XO Sklar, P Scolnick, EM TI Small-molecule screening using neuronal cells to assess candidate genes relevant to psychiatric disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, MIT, Broad Inst, Cambridge, MA 02129 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Charlestown, MA 02129 USA. MIT, Dept Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM haggarty@broad.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 85 EP 85 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300305 ER PT J AU Perlis, RH Fagerness, J Hamill, S Yamaki, L Sklar, P Fava, M Smoller, JW AF Perlis, RH Fagerness, J Hamill, S Yamaki, L Sklar, P Fava, M Smoller, JW TI Anger endophenotypes and single nucleotide polymorphisms in cAMP response element binding protein (CREB) in major depressive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM rperlis@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 106 EP 107 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300383 ER PT J AU Doyle, AE Faraone, SV Seidman, LJ Monuteaux, MC Jakubowski, A Biederman, J AF Doyle, AE Faraone, SV Seidman, LJ Monuteaux, MC Jakubowski, A Biederman, J TI Familial aggregation of ADHD symptoms and neuropsychological functions SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. SUNY Upstate Univ, Syracuse, NY USA. EM doylea@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 110 EP 110 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300396 ER PT J AU Koenen, KC Saxe, G Purcell, SM Smoller, JW Bartholomew, D Miller, A Hall, E Kaplow, J Bosquet, M Moulton, S Baldwin, C AF Koenen, KC Saxe, G Purcell, SM Smoller, JW Bartholomew, D Miller, A Hall, E Kaplow, J Bosquet, M Moulton, S Baldwin, C TI Polymorphisms in FKBP5 are associated with peri-traumatic dissociation in medically injured children SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Boston Univ, Med Ctr, Dept Pediat Surg, Boston, MA 02215 USA. Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02215 USA. EM kkoenen@hsph.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 114 EP 114 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300409 ER PT J AU Middleton, FA Pato, MT Fanous, A Gentile, KL Morley, CP Medeiros, HM Azevedo, MH Sklar, P Pato, CN AF Middleton, FA Pato, MT Fanous, A Gentile, KL Morley, CP Medeiros, HM Azevedo, MH Sklar, P Pato, CN TI Detection of significant linkage to chromosome 18q in Portuguese families with schizophrenia and dissociation from 5q linkage based on mode of inheritance and number of affecteds per family SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Upstate Med Univ, Syracuse, NY USA. Georgetown Univ, Washington, DC 20057 USA. Univ Coimbra, P-3000 Coimbra, Portugal. Broad Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM middletf@upstate.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 128 EP 128 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300463 ER PT J AU Sachs, NA Holmes, SE Sklar, P Waggoner, S Pato, MT Pato, CN Wildenauer, DB Schwab, SG Dickerson, F Yolken, RH Leister, FJ Nimgaonkar, VL Sawa, A Ross, CA DeLisi, LE Margolis, RL AF Sachs, NA Holmes, SE Sklar, P Waggoner, S Pato, MT Pato, CN Wildenauer, DB Schwab, SG Dickerson, F Yolken, RH Leister, FJ Nimgaonkar, VL Sawa, A Ross, CA DeLisi, LE Margolis, RL TI A frameshift mutation in disrupted in schizophrenia 1 in an American family with schizophrenia and schizoaffective disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21205 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. SUNY Syracuse, Dept Psychiat, Syracuse, NY USA. Georgetown Univ, Dept Psychiat, Washington, DC USA. Vet Adm Med Ctr, Washington, DC 20422 USA. Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. Univ Western Australia, Ctr Clin Res Neurosci, Perth, WA 6009, Australia. Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. Sheppard Pratt Hlth Syst, Stanley Res Ctr, Baltimore, MD 21204 USA. Johns Hopkins Sch Med, Dept Pediat, Stanley Neurovirol Lab, Baltimore, MD USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NYU, Dept Psychiat, New York, NY 10016 USA. EM nsachs2@jhmi.edu RI Ross, Christopher/H-8395-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP 5 PY 2005 VL 138B IS 1 BP 133 EP 134 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 971BY UT WOS:000232357300483 ER PT J AU Feske, S Prakriya, M Rao, A Lewis, RS AF Feske, S Prakriya, M Rao, A Lewis, RS TI A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INOSITOL TRISPHOSPHATE RECEPTOR; CAPACITATIVE CALCIUM-ENTRY; POTASSIUM CHANNELS; STORE DEPLETION; PORE PROPERTIES; MIC CHANNELS; ION-CHANNEL; MAST-CELLS; LYMPHOCYTES; RELEASE AB Engagement of the TCR triggers sustained Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels, which helps drive gene expression underlying the T cell response to pathogens. The identity and activation mechanism of CRAC channels at a molecular level are unknown. We have analyzed ion channel expression and function in T cells from SCID patients which display 1-2% of the normal level of Ca2+ influx and severely impaired T cell activation. The lack of Ca2+ influx is not due to deficient regulation of Ca2+ stores or expression of several genes implicated in controlling Ca2+ entry in lymphocytes (kcna3/Kv1.3, kcnn4/IKCa1, trpc1, trpc3, trpv6, stim1). Instead, electrophysiologic measurements show that the influx defect is due to a nearly complete absence of functional CRAC channels. The lack of CRAC channel activity is correlated with diminished voltage sensitivity and slowed activation kinetics of the voltage-dependent Kv1.3 channel. These results demonstrate that CRAC channels provide the major, if not sole, pathway for Ca2+ entry activated by the TCR in human T cells. They also offer evidence for a functional link between CRAC and Kv1.3 channels, and establish a model system for molecular genetic studies of the CRAC channel. C1 Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lewis, RS (reprint author), Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA. EM rslewis@stanford.edu OI Feske, Stefan/0000-0001-5431-8178 FU NIAID NIH HHS [AI054933, AI40127, R01 AI040127, R21 AI054933]; NICHD NIH HHS [HD39685]; NIGMS NIH HHS [GM45374, R01 GM045374, R37 GM045374] NR 54 TC 142 Z9 150 U1 1 U2 3 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 SEP 5 PY 2005 VL 202 IS 5 BP 651 EP 662 DI 10.1084/jem.20050687 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 965PM UT WOS:000231962700009 PM 16147976 ER PT J AU Hulgan, T Haas, DW Haines, JL Ritchie, MD Robbins, GK Shafer, RW Clifford, D Kallianpur, AR Summar, M Canter, JA AF Hulgan, T Haas, DW Haines, JL Ritchie, MD Robbins, GK Shafer, RW Clifford, D Kallianpur, AR Summar, M Canter, JA TI Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study SO AIDS LA English DT Article; Proceedings Paper CT 12th Conference on Retroviruses and Opportunistic Infections CY FEB 22-25, 2005 CL Boston, MA DE HIV; reverse transcriptase inhibitors; peripheral neuropathies; drug toxicity; mitochondrial DNA; pharmacogenetics ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEREDITARY OPTIC NEUROPATHY; REVERSE-TRANSCRIPTASE INHIBITORS; SEQUENTIAL 3-DRUG REGIMENS; PARKINSONS-DISEASE; NUCLEOSIDE ANALOGS; DNA POLYMORPHISMS; HIV-1 INFECTION; INITIAL THERAPY; HUMAN-EVOLUTION AB Objective: HIV nucleoside reverse transcriptase inhibitors (NRTI) can cause peripheral neuropathy that is a result of mitochondrial injury. Polymorphisms in the mitochondrial genome define haplogroups that may have functional implications. The objective of this study was to determine if NRTI-associated peripheral neuropathy is associated with European mitochondrial haplogroups. Design: Case-control study of Adult AIDS Clinical Trials Group (ACTG) study 384 and ACTG Human DNA Repository participants. Methods: ACTG study 384 was a treatment strategy trial of antiretroviral therapy with didanosine (ddl) plus stavudine (d4T) or zidovudine plus lamivudine given with efavirenz, nelfinavir, or both. Subjects were followed for up to 3 years. Peripheral neuropathy was ascertained based on signs and symptoms. For this analysis, polymorphisms that define European mitochondrial haplogroups were characterized in a majority of ACTG 384 participants, and associations with peripheral neuropathy were assessed using logistic regression. Results: A total of 509 subjects were included in this analysis of whom 250 (49%) were self-identified as white, non-Hispanic. Mitochondrial haplogroup T was more frequent in subjects who developed peripheral neuropathy. Among 137 white subjects randomized to receive ddl plus d4T, 20.8% of those who developed peripheral neuropathy belonged to mitochondrial haplogroup T compared to 4.5% of control subjects (odds ratio, 5.4; 95% confidence interval, 1.4-25.1; P = 0.009). Independent predictors of peripheral neuropathy were randomization to receive ddl plus d4T, older age, and mitochondrial haplogroup Conclusions: A common European mitochondrial haplogroup may predict NRTI-associated peripheral neuropathy. Future studies should validate this relationship, and evaluate non-European mitochondrial haplogroups and other NRTI toxicities. (c) 2005 Lippincott Williams & Wilkins. C1 Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, Nashville, TN 37203 USA. Vanderbilt Univ, Sch Med, Ctr Hlth Serv Res, Nashville, TN 37203 USA. Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37203 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37203 USA. Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37203 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Stanford Univ, Dept Med Infect Dis, Stanford, CA 94305 USA. Washington Univ, Sch Med, Dept Neurol & Neurol Surg, St Louis, MO 63130 USA. Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med & Publ Hlth, Nashville, TN 37203 USA. RP Hulgan, T (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, 345 24th Ave N,Suite 105, Nashville, TN 37203 USA. EM todd.hulgan@vanderbilt.edu RI Robbins, Gregory/F-7988-2011; Ritchie, Marylyn/C-1114-2012; Haines, Jonathan/C-3374-2012; Hulgan, Todd/B-3947-2014 OI Hulgan, Todd/0000-0002-3339-067X FU NCCIH NIH HHS [AT002508]; NCRR NIH HHS [U54RR019453]; NIAID NIH HHS [AI25903, AI38858, AI46339, AI54999]; NINDS NIH HHS [NS32228] NR 48 TC 92 Z9 100 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 2 PY 2005 VL 19 IS 13 BP 1341 EP 1349 DI 10.1097/01.aids.0000180786.02930.a1 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 970MK UT WOS:000232314100001 PM 16103764 ER PT J AU Lipskaia, L del Monte, F Capiod, T Yacoubi, S Hadri, L Hours, M Hajjar, RJ Lompre, AM AF Lipskaia, L del Monte, F Capiod, T Yacoubi, S Hadri, L Hours, M Hajjar, RJ Lompre, AM TI Sarco/endoplasmic reticulum Ca2+-ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in the rat SO CIRCULATION RESEARCH LA English DT Article DE vascular smooth muscle cell proliferation; gene transfer; SERCA2a; calcium signaling; nuclear factor of activated T-cells ID ACTIVATED T-CELLS; SARCOPLASMIC-RETICULUM; HEART-FAILURE; TRANSCRIPTION FACTORS; CARDIAC-HYPERTROPHY; RYANODINE RECEPTORS; CA-2+-ATPASE GENE; NUCLEAR EXPORT; CA2+ WAVES; IN-VIVO AB Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of vascular disorders and is associated with major alterations in Ca2+ handling supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine the importance of SERCA2a in neointima formation, we have prevented loss of its expression by adenoviral gene transfer in a model of balloon injury of the rat carotid artery. Two weeks after injury, the intima/media ratio was significantly lower in SERCA2a-infected than in injured noninfected or injured beta-galactosidase-infected carotids (0.29 +/- 0.04 versus 0.89 +/- 0.19 and 0.72 +/- 0.14, respectively; P < 0.05), and was comparable to that observed in control carotids (0.21 +/- 0.03). The pathways leading to proliferation were analyzed in serum-stimulated VSMC. Forced expression of SERCA2a arrested cell cycle at the G1 phase and prevented apoptosis. SERCA2a inhibits proliferation through inactivation of calcineurin ( PP2B) and its target transcription factor NFAT ( nuclear factor of activated T-cells) resulting in lowering of cyclin D1 and pRb levels. By using NFAT-competing peptide VIVIT, we showed that NFAT activity is strongly required to promote VSMC proliferation. In conclusion, we provide the first evidence that increasing SERCA2a activity inhibits VSMC proliferation and balloon injury-induced neointima formation. C1 UPMC, U621, Fac Med Pitie Salpetriere, IFR 14,INSERM, F-75634 Paris, France. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. USTL, INSERM, EMI 0228, IFR 118, Villeneuve Dascq, France. Univ Paris 11, IFR FR46, Serv Cytomet, IBAIC, Orsay, France. RP Lompre, AM (reprint author), UPMC, U621, Fac Med Pitie Salpetriere, IFR 14,INSERM, 91 Hop, F-75634 Paris, France. EM lompre@chups.jussieu.fr RI LOMPRE, Anne-Marie/H-2872-2013 FU NHLBI NIH HHS [HL 071763, HL-057623] NR 45 TC 60 Z9 62 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 2 PY 2005 VL 97 IS 5 BP 488 EP 495 DI 10.1161/01.RES.0000180663.42594.aa PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 960OC UT WOS:000231602000013 PM 16081870 ER PT J AU Turner, JH Raymond, JR AF Turner, JH Raymond, JR TI Interaction of calmodulin with the serotonin 5-hydroxytryptamine(2A) receptor - A putative regulator of G protein coupling and receptor phosphorylation by protein kinase C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 2ND INTRACELLULAR LOOP; GROWTH-FACTOR RECEPTOR; ARACHIDONIC-ACID METABOLISM; MEDIATED ERK ACTIVATION; CYCLIC-AMP ACCUMULATION; RENAL MESANGIAL CELLS; 5-HT2A RECEPTOR; PHOSPHOLIPASE-C; SIGNAL-TRANSDUCTION; CYTOPLASMIC TAIL AB The 5-hydroxytryptamine(2A) (5-HT2A) receptor is a G(q/11)-coupled serotonin receptor that activates phospholipase C and increases diacylglycerol formation. In this report, we demonstrated that calmodulin (CaM) co-immunoprecipitates with the 5-HT2A receptor in NIH-3T3 fibroblasts in an agonist-dependent manner and that the receptor contains two putative CaM binding regions. The putative CaM binding regions of the 5-HT2A receptor are localized to the second intracellular loop and carboxyl terminus. In an in vitro binding assay peptides encompassing the putative second intracellular loop (i2) and carboxyl-terminal (ct) CaM binding regions bound CaM in a Ca2+-dependent manner. The i2 peptide bound with apparent higher affinity and shifted the mobility of CaM in a nondenaturing gel shift assay. Fluorescence emission spectral analyses of dansyl-CaM showed apparent K-D values of 65 +/- 30 nM for the i2 peptide and 168 +/- 38 nM for the ct peptide. The ct CaM-binding domain overlaps with a putative protein kinase C (PKC) site, which was readily phosphorylated by PKC in vitro. CaM binding and phosphorylation of the ct peptide were found to be antagonistic, suggesting a putative role for CaM in the regulation of 5-HT2A receptor phosphorylation and desensitization. Finally, we showed that CaM decreases 5-HT2A receptor-mediated [S-35]GTP gamma S binding to NIH-3T3 cell membranes, supporting a possible role for CaM in regulating receptor-G protein coupling. These data indicate that the serotonin 5-HT2A receptor contains two high affinity CaM-binding domains that may play important roles in signaling and function. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. RP Raymond, JR (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, 96 Jonathan Lucas St,Rm 829 CSB,POB 250623, Charleston, SC 29425 USA. EM raymondj@musc.edu FU NIDDK NIH HHS [DK52448]; NIGMS NIH HHS [GM63909, GM08716] NR 75 TC 48 Z9 50 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 2005 VL 280 IS 35 BP 30741 EP 30750 DI 10.1074/jbc.M50169200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 958ZX UT WOS:000231487800013 PM 15970592 ER PT J AU Tatulian, SA Qin, S Pande, AH He, XM AF Tatulian, SA Qin, S Pande, AH He, XM TI Positioning membrane proteins by novel protein engineering and biophysical approaches SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE membrane protein; orientation; insertion; polarized FTIR; fluorescence quenching ID RELAXATION MAGNETIC-RESONANCE; PANCREATIC PHOSPHOLIPASE A(2); REFLECTION FTIR SPECTROSCOPY; LIPID BILAYERS; X-RAY; INFRARED-SPECTROSCOPY; NMR-SPECTROSCOPY; GATING MECHANISM; ORIENTATION; BINDING AB Membrane proteins are unique, in that they can function properly only when they are bound to cellular membranes in a distinct manner. Therefore, positioning of, membrane proteins with respect to the membrane is required in addition to the three-dimensional structures in order to understand their detailed molecular mechanisms. Atomic-resolution structures of membrane proteins that have been determined to date provide the atom coordinates in arbitrary coordinate systems with no relation to the membrane and therefore provide little or no information on how the protein would interact with the membrane. This is especially true for peripheral membrane proteins, because they, unlike integral proteins, are devoid of well-defined hydrophobic transmembrane domains. Here, we present a novel technique for determination of the configuration of a protein-membrane complex that involves protein ligation, segmental isotope labeling, polarized infrared spectroscopy, membrane depth dependent fluorescence quenching, and analytical geometry algorithms. We have applied this approach to determine the structure of a membranebound phospholipase A(2). Our results provide an unprecedented structure of a membrane-bound protein in which the z-coordinate of each atom is the distance from the membrane center and therefore allows precise location of each amino acid relative to the membrane. Given the functional significance of the orientation and location of membrane-bound proteins with respect to the membrane, we propose to specify this structural feature as the "quinary" structure of membrane proteins. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32826 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biol Mol, Boston, MA 02114 USA. Univ Cent Florida, Dept Chem, Orlando, FL 32816 USA. RP Tatulian, SA (reprint author), Univ Cent Florida, Biomol Sci Ctr, 12722 Res Pkwy, Orlando, FL 32826 USA. EM statulia@mail.ucf.edu FU NHLBI NIH HHS [HL65524] NR 45 TC 30 Z9 30 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 2 PY 2005 VL 351 IS 5 BP 939 EP 947 DI 10.1016/j.jmb.2005.06.080 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959LN UT WOS:000231519300001 PM 16055150 ER PT J AU Nagurney, JT Brown, DFM Sane, S Weiner, JB Wang, AC Chang, YC AF Nagurney, JT Brown, DFM Sane, S Weiner, JB Wang, AC Chang, YC TI The accuracy and completeness of data collected by prospective and retrospective methods SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY, 2003 CL BOSTON, MA SP Soc Acad Emergency Med DE data collection; retrospective; prospective; bias; precision; methodology; myocardial infarction ID MEDICAL RECORDS; CHEST-PAIN; MYOCARDIAL-INFARCTION; STANDARDIZED PATIENTS; EMERGENCY-DEPARTMENT; EPIDEMIOLOGIC DATA; PROSPECTIVE COHORT; CHART ABSTRACTION; RECALL BIAS; RELIABILITY AB Objectives: To describe and test a model that compares the accuracy of data gathered prospectively versus retrospectively among adult emergency department patients admitted with chest pain. Methods: The authors developed a model of information flow from subject to medical record to the clinical study case report form, based on a literature review. To test this model, a bidirectional (prospective and retrospective) study was conducted, enrolling all eligible adult patients who were admitted with a chief complaint of chest pain. The authors interviewed patients in the emergency department to determine their chest pain history and established a prospective database; this was considered the criterion standard. Then, patient medical records were reviewed to determine the accuracy and completeness of the information available through a retrospective medical record review. Results: The model described applies the concepts of reliability and validity to information passed on by the study subject, the clinician, and the medical record abstractor. This study was comprised of 104 subjects, of which 63% were men and the median age was 63 years. Subjects were uncertain of responses for 0-8% of questions and responded differently upon reinterview for subsets of questions 0-30% of the time. The sensitivity of the medical record for risk factors for coronary artery disease was 0.77 to 0.93. Among the 88 subjects (85%) who indicated that their chest pain was substernal or left chest, the medical record described this location in 44%. Timing of the chest pain was the most difficult item to accurately capture from the medical record. Conclusions: Information obtained retrospectively from the abstraction of medical records is measurably less accurate than information obtained prospectively from research subjects. For certain items, more than half of the information is not available. This loss of information is related to the data types included in the study and by the assumptions that a researcher performing a retrospective study makes about implied versus explicitly stated responses. A model of information flow that incorporates the concepts of reliability and validity can be used to measure some of the loss of information that occurs at each step along the way from subject to clinician to medical record abstractor. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Princeton Univ, Princeton, NJ 08544 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, 55 Fruit St, Boston, MA 02115 USA. EM nagurney.john@mgh.harvard.edu NR 40 TC 24 Z9 24 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2005 VL 12 IS 9 BP 884 EP 895 DI 10.1197/j.aem.2005.04.021 PG 12 WC Emergency Medicine SC Emergency Medicine GA 962GT UT WOS:000231719700015 PM 16141025 ER PT J AU Park, ER Betancourt, JR Kim, MK Maina, AW Blumenthal, D Weissman, JS AF Park, ER Betancourt, JR Kim, MK Maina, AW Blumenthal, D Weissman, JS TI Mixed messages: Residents' experiences learning cross-cultural care SO ACADEMIC MEDICINE LA English DT Article ID QUALITATIVE RESEARCH; MEDICAL-EDUCATION; HEALTH AB Purpose An Institute of Medicine report issued in 2002 cited cross-cultural training as a mechanism to address racial and ethnic disparities in health care, but little is known about residents' training and capabilities to provide quality care to diverse populations. This article explores a select group of residents' perceptions of their preparedness to deliver quality care to diverse populations. Method Seven focus groups and ten individual interviews were conducted with 68 residents in locations nationwide. Qualitative analysis of focus-group and individual interview transcripts was performed to assess residents' perceptions of (1) preparedness to deliver care to diverse patients; (2) educational climate; and (3) training experiences. Results Most residents in this study noted the importance of cross-cultural care yet reported little formal training in this area. Residents wanted more formal training yet expressed concern that culture-specific training could lead to stereotyping. Most residents had developed ad hoc, informal skills to care for diverse patients. Although residents perceived institutional endorsement, they sensed it was a low priority due to lack of time and resources. Conclusions Residents in this study reported receiving mixed messages about cross-cultural care. They were told it is important, yet they received little formal training and did not have time to treat diverse patients in a culturally sensitive manner. As a result, many developed coping behaviors rather than skills based on formally taught best practices. Training environments need to increase training to enhance residents' preparedness to deliver high-quality cross-cultural care if the medical profession is to achieve the goals set by the Institute of Medicine. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Dept Med, Sch Med, Boston, MA 02114 USA. Ewha Womans Univ, Seoul, South Korea. Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02114 USA. RP Park, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org NR 25 TC 40 Z9 41 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2005 VL 80 IS 9 BP 874 EP 880 DI 10.1097/00001888-200509000-00019 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 961DS UT WOS:000231642700015 PM 16123471 ER PT J AU Mueller, W Riemenschneider, MJ Nutt, CL Louis, DN AF Mueller, W Riemenschneider, MJ Nutt, CL Louis, DN TI 5 ' Aza-dc treatment and microarray analysis unveil epigenome in GBM SO ACTA NEUROPATHOLOGICA LA English DT Meeting Abstract CT 50th Annual Meeting of the German-Society-of-Neuropathology-and-Neuroanatomy CY OCT 05-08, 2005 CL Graz, AUSTRIA SP German Soc Neuropathol Neuroanatomy C1 Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Hosp Charite, Dept Neuropathol, D-13353 Berlin, Germany. RI Nutt, Catherine/K-8794-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD SEP PY 2005 VL 110 IS 3 BP 336 EP 336 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 968KD UT WOS:000232160500075 ER PT J AU Levine, AJ Hinkin, CH Castellon, SA Mason, KI Lam, MN Perkins, A Robinet, M Longshore, D Newton, T Myers, H Durvasula, RS Hardy, DJ AF Levine, AJ Hinkin, CH Castellon, SA Mason, KI Lam, MN Perkins, A Robinet, M Longshore, D Newton, T Myers, H Durvasula, RS Hardy, DJ TI Variations in patterns of highly active antiretroviral therapy (HAART) adherence SO AIDS AND BEHAVIOR LA English DT Article DE antiretroviral therapy; HAART; adherence; HIV; substance abuse ID MEDICATION ADHERENCE; PROTEASE INHIBITORS; VIRAL LOAD; PREDICTORS; COHORT; ADULTS AB Strict adherence to highly active antiretroviral therapy ( HAART) is necessary for successful suppression of HIV replication. A large number of individuals are not adherent, however, and the reasons for non-adherence are varied and complex. We utilized cluster analyses to identify subgroups of adherers in a sample of 222 HIV positive individuals whose HAART use was electronically monitored. Five distinct subgroups were identified, with characteristic variations across the week and over the course of the 4-week study. Additional comparisons of demographic and behavioral variables found the worst adherers to have higher rates of substance use, and that a group with higher rates of cognitive impairment had a consistent drop in adherence during the weekends. In addition, the group with the best adherence had more individuals over the age of 50 years. The results of the current study indicate that distinct subgroups of adherers may exist, and suggest that interventions designed to improve adherence can be designed to accommodate this variability in behavior. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Neuropsychiat Inst, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Calif State Univ Los Angeles, Los Angeles, CA 90032 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Levine, AJ (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Neuropsychiat Inst, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. EM ajlevine@mednet.ucla.edu OI newton, thomas/0000-0002-3198-5901 FU NIDA NIH HHS [R01 DA013799, R01 DA13799]; NIMH NIH HHS [R01 MH058552, R01 MH58552] NR 16 TC 41 Z9 44 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD SEP PY 2005 VL 9 IS 3 BP 355 EP 362 DI 10.1007/s10461-005-9009-y PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 980CE UT WOS:000232990700010 PM 16088365 ER PT J AU Corless, IB Kirksey, KM Kemppainen, J Nicholas, PK McGibbon, C Davis, SM Dolan, S AF Corless, IB Kirksey, KM Kemppainen, J Nicholas, PK McGibbon, C Davis, SM Dolan, S TI Lipodystrophy-associated symptoms and medication adherence in HIV/AIDS SO AIDS PATIENT CARE AND STDS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; QUALITY-OF-LIFE; IMMUNODEFICIENCY-VIRUS INFECTION; METABOLIC ABNORMALITIES; CARDIOVASCULAR-DISEASE; INHIBITOR THERAPY; BODY-COMPOSITION; FAT DISTRIBUTION; HIV; STAVUDINE AB Lipodystrophy-associated manifestations remain a challenge for persons infected with HIV disease and their care providers. Symptomatic HIV disease and side effects of medications are implicated in antiretroviral medication nonadherence. This study examined the relationship between time since initial diagnosis with HIV, presence and type of lipodystrophic symptoms, and adherence to medication regimens in persons with HIV/AIDS. Using a cross-sectional, descriptive design, the sample was composed of 165 persons from three outpatient HIV settings in Boston, Massachusetts; Fresno, California; and Victoria, Texas. Participants completed a questionnaire comprised of sociodemographic questions, adherence scales, quality-of-life scales, and open-ended questions regarding presence and types of lipodystrophy-associated symptoms, and how these physical changes made them feel. Adherence was moderate with a mean score of 1.44 (standard deviation [SD] +/- 1.33) on the Morisky Medication Adherence Scale (MMAS). The MMAS is a Likert-type scale ranging from 0 - 4, with "0" indicating very adherent. This finding indicated that the participants took their medications moderately well despite self-reports of significant numbers of HIV disease and treatment-related body fat changes. Time since initial diagnosis was 8.86 +/- 5.55 years and was not related to adherence. Nor did the type of lipodystrophic symptoms affect adherence. Quality of life however, was significantly related to adherence suggesting an approach that might be taken to improve adherence. C1 MGH Inst Hlth Profess, Boston, MA 02115 USA. Harris Cty Hosp Dist, Houston, TX USA. Univ N Carolina, Wilmington, NC 28401 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Corless, IB (reprint author), MGH Inst Hlth Profess, Boston, MA 02115 USA. EM Icorless@mghihp.edu OI Corless, Inge/0000-0003-0438-2037 NR 55 TC 33 Z9 33 U1 2 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2005 VL 19 IS 9 BP 577 EP 586 DI 10.1089/apc.2005.19.577 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 966YI UT WOS:000232058300005 PM 16164384 ER PT J AU Canto, JG Kiefe, CI AF Canto, JG Kiefe, CI TI Door-to-needle time in myocardial infarction: Is there an ideal benchmark? SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID NATIONAL REGISTRY; REPERFUSION THERAPY; MORTALITY C1 Watson Clin, Ctr Cardiovasc Prevent Res & Educ, Lakeland, FL 33801 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham Vet Affairs Med Ctr, Div Cardiovasc Dis, Birmingham, AL USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham Vet Affairs Med Ctr, Div Prevent Med, Birmingham, AL USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. RP Canto, JG (reprint author), Watson Clin, Ctr Cardiovasc Prevent Res & Educ, Lakeland, FL 33801 USA. NR 10 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 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2005 VL 150 IS 3 BP 365 EP 367 DI 10.1016/j.ahj.2005.04.026 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 970WQ UT WOS:000232343500001 PM 16169308 ER PT J AU Heist, EK Fan, DL Mela, T Arzola-Castaner, D Reddy, VY Mansour, M Picard, MH Ruskin, JN Singh, JP AF Heist, EK Fan, DL Mela, T Arzola-Castaner, D Reddy, VY Mansour, M Picard, MH Ruskin, JN Singh, JP TI Radiographic left ventricular-right ventricular interlead distance predicts the acute hemodynamic response to cardiac resynchronization therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; DILATED CARDIOMYOPATHY; SYSTOLIC FUNCTION; SITE; DYSSYNCHRONY; DELAY AB Placement of left ventricular (LV) and right ventricular (RV) leads with maximal interlead separation is frequently sought during cardiac resynchronization therapy (CRT), but few published data are available to support this. This study examined the relation between LV and RV lead separation and the acute effects of CRT on cardiac contractility. A total of 51 consecutive patients who underwent CRT for standard indications with sufficient mitral regurgitation for echocardiographic assessment of contractility (using Doppler profiles of mitral regurgitation as a percentage of change in dP/dt [Delta dP/dt] with CRT on and off), successful transvenous LV lead placement, and postprocedural chest radiography were evaluated. The separation of the LV and RV lead tips (direct interlead distance and horizontal and vertical components) was determined on postprocedural posteroanterior and lateral radiographs. The corrected direct LV-RV interlead distance on the lateral radiograph was correlated with the Delta dP/dt (n = 51, r = 0.43, p = 0.002). The lateral interlead distance in the horizontal plane (r = 0.5 8, p < 0.0001), but not the vertical plane (r = - 0.28, p = NS), correlated with the AdP/dt. The corrected horizontal interlead distance on the lateral film was greater in acute hemodynamic responders to CRT (Delta dP/dt > 25%) compared with nonresponders (14.4 +/- 5.4 vs 9.2 +/- 5.8 cm, p = 0.002). Other LV-RV measures on the posteroanterior and lateral radiographs did not correlate with the Delta dP/dt. Use of these findings may help to guide the sites of LV and RV lead placement to maximize the benefit derived from CRT. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Echocardiography Serv, Boston, MA USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02115 USA. EM jsingh@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 17 TC 39 Z9 41 U1 0 U2 1 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 SEP 1 PY 2005 VL 96 IS 5 BP 685 EP 690 DI 10.1016/j.amjcard.2005.04.045 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 961DX UT WOS:000231643200017 PM 16125496 ER PT J AU Wolf, RL Cauley, JA Pettinger, M Jackson, R Lacroix, A Leboff, MS Lewis, CE Nevitt, MC Simon, JA Stone, KL Wactawski-Wende, J AF Wolf, RL Cauley, JA Pettinger, M Jackson, R Lacroix, A Leboff, MS Lewis, CE Nevitt, MC Simon, JA Stone, KL Wactawski-Wende, J TI Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women's Health Initiative SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE antioxidants; diet; serum; bone mineral density; osteoporosis; Women's Health Initiative ID ASCORBIC-ACID CONCENTRATIONS; CALCIUM SUPPLEMENTATION; POSTMENOPAUSAL WOMEN; ORAL-CONTRACEPTIVES; HIP FRACTURE; ELDERLY-WOMEN; PLASMA; RISK; OSTEOPOROSIS; AGE AB Background: Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass. Objective: This study cross-sectionally examined whether higher dietary intakes, total intakes, and serum concentrations of antioxidants may be associated with higher bone mineral density (BMD). Design: Total hip (and subregions), spine, and total-body BMDs were measured in 11068 women aged 50-79 y enrolled in,, the Women's Health Initiative Observational Study and Clinical Trial at 3 clinics. Antioxidant intakes from diet (vitamin A, retinol, beta-carotene. vitamin C, vitamin E, and selenium) were estimated by using a self-reported food-frequency questionnaire. Antioxidants from supplements were estimated with an interviewer-administered questionnaire. A random subset (n = 379) had serum concentrations of retinol, carotenoids, and tocopherols measured. Results: After adjustment for important BMD-related covariates, increasing intakes of antioxidants were not independently associated with BMD. A significant interaction effect was observed between intake of total vitamin C (lower three-fourths compared with highest one-fourth) and use of hormone therapy (HT) (P < 0.01). The beneficial effect of current FIT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body (P < 0.045), spine (P = 0.03), and total-hip BMDs (P = 0.029). Conclusions: Our results do not support independent associations between dietary intake, total intake, or serum concentrations of antioxidants and BMD in women participating in the Women's Health Initiative. The extent to which HT use may interact with vitamin C intake and BMD warrants further exploration. C1 Columbia Univ, Teachers Coll, Dept Hlth & Behav Studies, Nutr Program, New York, NY 10027 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Ohio State Univ, Columbus, OH 43210 USA. Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. SUNY Buffalo, Buffalo, NY USA. RP Wolf, RL (reprint author), Columbia Univ, Teachers Coll, Dept Hlth & Behav Studies, Nutr Program, 525 W 120th St,Box 137, New York, NY 10027 USA. EM wolf@exchange.tc.columbia.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [5T32AG000181-15] NR 47 TC 71 Z9 77 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2005 VL 82 IS 3 BP 581 EP 588 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 963NB UT WOS:000231809900015 PM 16155271 ER PT J AU MacLean, CH Mojica, WA Newberry, SJ Pencharz, J Garland, RH Tu, WL Hilton, LG Gralnek, IM Rhodes, S Khanna, P Morton, SC AF MacLean, CH Mojica, WA Newberry, SJ Pencharz, J Garland, RH Tu, WL Hilton, LG Gralnek, IM Rhodes, S Khanna, P Morton, SC TI Systematic review of the effects of n-3 fatty acids in inflammatory bowel disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review DE n-3 fatty acids; inflammatory bowel disease ID ULCERATIVE-COLITIS; FISH-OIL; CROHNS-DISEASE; DOUBLE-BLIND; EMPIRICAL-EVIDENCE; RANDOMIZED-TRIALS; SUPPLEMENTATION; EPIDEMIOLOGY; REMISSION; QUALITY AB Background: n - 3 Fatty acids are purported to have health effects in patients with inflammatory bowel disease (IBD), but Studies have reported mixed results. Objective: We aimed to synthesize published and unpublished evidence to determine estimates of the effect of n-3 fatty acids on clinical outcomes in IBD and whether n-3 fatty acids modify the effects of or need for treatment with other agents. Design: Computerized databases were searched for studies of n-3 fatty acids in immune-mediated diseases from 1966 to 2003. We also contacted experts in the nutraceutical industry to identify unpublished studies, however, none were identified. Results: Reviewers identified 13 controlled trials that assessed the effects of n-3 fatty acids on clinical, sigmoidoscopic, or histologic scores, rates of induced remission or relapse; or requirements for steroids and other immunosuppressive agents in Crohn disease or ulcerative colitis. Most clinical trials were of good quality. Fewer than 6 were identified that assessed the effects of n-3 fatty acids on any single outcome of clinical, endoscopic, or histologic scores or remission or relapse rates. Consistent across 3 studies was the finding that n-3 fatty acids reduce corticosteroid requirements, although statistical significance was shown in only 1 of these studies. Conclusion: The available data are insufficient to draw conclusions about the effects of n-3 fatty acids on clinical, endoscopic, or histologic scores or remission or relapse rates. C1 RAND Hlth, Santa Monica, CA 90407 USA. So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Greater Los Angeles VA Healthcare Syst, Div Rheumatol, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. Toronto Gen Hosp, Toronto Gen Res Inst, Clin Decis Making & Healthcare, Toronto, ON, Canada. Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON, Canada. RP MacLean, CH (reprint author), RAND Hlth, 1700 Main St,M23-C, Santa Monica, CA 90407 USA. EM maclean@rand.org NR 33 TC 69 Z9 73 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2005 VL 82 IS 3 BP 611 EP 619 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 963NB UT WOS:000231809900019 PM 16155275 ER PT J AU Schulze, MB Hoffmann, K Manson, JE Willett, WC Meigs, JB Weikert, C Heidemann, C Colditz, GA Hu, FB AF Schulze, MB Hoffmann, K Manson, JE Willett, WC Meigs, JB Weikert, C Heidemann, C Colditz, GA Hu, FB TI Dietary pattern, inflammation, and incidence of type 2 diabetes in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body mass index; diet pattern; incidence; inflammation; non-insulin-dependent diabetes mellitus; type 2 diabetes; prospective studies; questionnaires; reduced rank regression; risk factors ID WHOLE-GRAIN INTAKE; MIDDLE-AGED WOMEN; TOTAL-ENERGY-INTAKE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; ALCOHOL-CONSUMPTION; COFFEE CONSUMPTION; PHYSICAL-ACTIVITY; MEAT INTAKE AB Background: Inflammation is considered a key mechanism leading to type 2 diabetes, but dietary exposures that lead to inflammation and diabetes are largely unknown. Objective: Our objective was to investigate the relation between a dietary pattern associated with biomarkers of inflammation and the incidence of type 2 diabetes. Design: We conducted a nested case-control study of 656 cases of type 2 diabetes and 694 controls among women in the Nurses' Health Study and 2 prospective cohort studies of 35 340 women in the Nurses' Health Study and 89 311 women in the Nurses' Health Stud), [I who were followed for incident diabetes. Results: Through the use of reduced rank regression, we identified a dietary pattern that was strongly related to inflammatory markers in the nested case-control study. This pattern, which was high in sugar-sweetened soft drinks, refined grains, diet soft drinks, and processed meat but low in wine, coffee, cruciferous vegetables, and yellow vegetables, was associated with an increased risk of diabetes (multivariate-adjusted odds ratio comparing extreme quintiles: 3.09; 95% CI: 1.99. 4.79). We identified 1517 incident cases of confirmed type 2 diabetes in the Nurses' Health Study (458 991 person-years) and 724 incident cases in the Nurses' Health Study II (701 155 person-years). After adjustment for body mass index and other potential lifestyle confounders, the relative risks comparing extreme quintiles of the pattern were 2.56 (95% CI: 2.10, 3.12; P for trend < 0.001) in the Nurses' Health Study and 2.93 (95% CI: 2.18, 3.92; P for trend < 0.001) in the Nurses' Health Study II. Conclusion: The dietary pattern identified may increase chronic inflammation and raise the risk of developing type 2 diabetes. C1 German Inst Human Nutr Potsdam Rehbruecke, Dept Epidemiol, D-14558 Nuthetal, Germany. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Schulze, MB (reprint author), German Inst Human Nutr Potsdam Rehbruecke, Dept Epidemiol, Arthur Scheunert Allee 114-116, D-14558 Nuthetal, Germany. EM mschulze@mail.dife.de RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [R01 CA095589, CA50385, CA87969, P01 CA087969, R01 CA050385]; NHLBI NIH HHS [HL60712, R01 HL060712]; NIDDK NIH HHS [DK58845, R01 DK058845] NR 62 TC 202 Z9 206 U1 3 U2 25 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2005 VL 82 IS 3 BP 675 EP 684 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 963NB UT WOS:000231809900027 PM 16155283 ER PT J AU Greenberg, RA Livingston, DM AF Greenberg, RA Livingston, DM TI Functional analysis of the BRCA1 tumor suppressor network. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-and-Scientists CY JUN 09-11, 2005 CL Pittsburgh, PA C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2005 VL 124 IS 3 BP 469 EP 469 PG 1 WC Pathology SC Pathology GA 956ZH UT WOS:000231338300057 ER PT J AU Kanwal, F Gralnek, IM Hays, RD Dulai, GS Spiegel, BMR Bozzette, S Asch, S AF Kanwal, F Gralnek, IM Hays, RD Dulai, GS Spiegel, BMR Bozzette, S Asch, S TI Impact of chronic viral hepatitis on health-related quality of life in HIV: Results from a nationally representative sample SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; LOW-PREVALENCE DISEASES; STAGE LIVER-DISEASE; C VIRUS; INFECTED PATIENTS; SERVICES UTILIZATION; B-VIRUS; PROBABILITY SAMPLES; MEDICAL OUTCOMES AB BACKGROUND: Little is known about the health burden of chronic viral hepatitis in HIV-infected patients. We compared health-related quality of life (HRQOL) of patients with HIV and hepatitis C virus (HCV) or HIV and hepatitis B virus (HBV) coinfection to those with HIV monoinfection. METHODS: Using a nationally representative sample of 1,874 adults with HIV who completed a baseline and two follow-up interviews, we identified those with HIV monoinfection (n = 1,493), HIV-HCV coinfection (n = 279), and HIV-HBV coinfection (n = 122). We measured baseline and change over time scores for physical and mental health (PHS, MHS), overall quality of life (QOL), overall health, and disability days. To identify the independent effect of coinfection, we adjusted for demographic and clinical predictors of HRQOL using multivariable regression. RESULTS: Despite significant differences in socio-demographic characteristics between groups, there were no differences in the baseline scores for PHS, MHS, overall QOL, overall health, or disability days between groups. The HRQOL did not decline significantly over time for the HIV patients with or without HCV or HBV coinfection. All groups reported similar longitudinal changes in the HRQOL scores for all measures. CONCLUSIONS: We found no significant differences in disease burden as assessed by a generic HRQOL instrument between patients with HIV monoinfection and HIV-HCV or HIV-HBV coinfection. These data are relevant in counseling coinfected patients regarding the impact of coinfection on HRQOL, and are important in designing clinical trials and conducting cost-effectiveness analyses including this vulnerable cohort. C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Div Gastroenterol Hepatol, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med Hlth Serv Res, Los Angeles, CA USA. CURE Digest Dis Res, Los Angeles, CA USA. Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA USA. Univ Calif Los Angeles, Div Gen Internal Med Hlth Serv Res, Los Angeles, CA 90024 USA. RAND Corp, Hlth Sci Program, Santa Monica, CA USA. VA La Jolla Med Ctr, Div Internal Med Infect Dis, Los Angeles, CA USA. RP Kanwal, F (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215B, Los Angeles, CA 90073 USA. RI Hays, Ronald/D-5629-2013 FU NCRR NIH HHS [K23 RR0016188]; NIA NIH HHS [AG-02-004]; NIMHD NIH HHS [P20-MD00148-01] NR 47 TC 17 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 BP 1984 EP 1994 DI 10.1111/j.1572-0241.2005.41962.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BL UT WOS:000231853600016 PM 16128943 ER PT J AU Farraye, FA Andrews, C Shah, SA Becker, JM Bleday, R Ashley, S Hodin, R Eisenberg, M Berger, B Odze, RD AF Farraye, FA Andrews, C Shah, SA Becker, JM Bleday, R Ashley, S Hodin, R Eisenberg, M Berger, B Odze, RD TI Analysis of DNA mutations in stool is a novel method to detect neoplasia in patients with inflammatory bowel disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Boston Med Ctr, Boston, MA USA. Brown Univ, Providence, RI 02912 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lab Corp Amer, Res Triangle Pk, NC USA. Exact Sci, Marlborough, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 816 BP S302 EP S302 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502075 ER PT J AU Germano, P Lieu, S Million, M Oh, D Waschek, J Tache, Y Pisegna, J AF Germano, P Lieu, S Million, M Oh, D Waschek, J Tache, Y Pisegna, J TI PACAP and its receptor, PAC1 exert a protective effect in preventing dextran sulfate sodium (DSS)-induced colitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Univ Calif Los Angeles, David Geffen Sch Med, CURE DDRC, Div Digest Dis, Los Angeles, CA 90024 USA. VA Greater LA Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 837 BP S308 EP S309 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502095 ER PT J AU Go, MF Clark, H Christison, BBS Hatton-Ward, S Sonnenberg, N AF Go, MF Clark, H Christison, BBS Hatton-Ward, S Sonnenberg, N TI Prolonged exposure to H-pylori (Hp) in developing countries: Is there an increased risk of infection? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 VA SLC Hlth Care Syst, Salt Lake City, UT USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 95 BP S54 EP S55 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853500096 ER PT J AU Gralnek, IM Dulai, GS Fennerty, B Spiegel, BMR AF Gralnek, IM Dulai, GS Fennerty, B Spiegel, BMR TI Esomeprazole (ESO) versus alternative proton pump inhibitors (PPI) in erosive esophagitis (EE): A meta-analysis of trials reporting healing rates and symptom relief SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles, Los Angeles, CA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 742 BP S277 EP S277 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502001 ER PT J AU Kappelman, MD Watkins, JB Buie, TM AF Kappelman, MD Watkins, JB Buie, TM TI Celiac disease presenting as coagulopathy in a child with Down Syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 239 BP S101 EP S101 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853500240 ER PT J AU Loftis, JM Rifai, MA Hauser, P AF Loftis, JM Rifai, MA Hauser, P TI Depression and sustained viral response in patients with hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIMH, Off Clin Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 277 BP S114 EP S114 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853500278 ER PT J AU Machicado, GA Jensen, DM Hirabayashi, K AF Machicado, GA Jensen, DM Hirabayashi, K TI Randomized controlled study of a new InScope multi-clip applier, Olympus QuickClip2, MPEC, injection and combination therapy comparing hemostasis and healing of bleeding canine acute gastric ulcers SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Digest Dis Res Ctr, BA CURE, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 973 BP S355 EP S356 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502230 ER PT J AU Sandborn, W Sands, B Hanauer, S Bloomfeld, R AF Sandborn, W Sands, B Hanauer, S Bloomfeld, R TI The effectiveness of continuing the induction dose of Asacol into the maintenance phase: Results from the community setting SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 846 BP S312 EP S312 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502104 ER PT J AU Sandborn, WJ Feagan, BG Olson, A Johanns, J Travers, S Present, D Sands, BE Rutgeerts, P AF Sandborn, WJ Feagan, BG Olson, A Johanns, J Travers, S Present, D Sands, BE Rutgeerts, P TI A randomized placebo-controlled trial of infliximab therapy for active ulcerative colitis: ACT 1 trial results through week 54 SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Univ Western Ontario, Robarts Res Inst, London, ON N6A 3K7, Canada. Mayo Clin, Rochester, MN USA. Centocor Inc, Clin Res & Dev, Malvern, PA 19355 USA. Centocor Inc, Biostat, Malvern, PA 19355 USA. Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Katholieke Univ Leuven Hosp, Louvain, Belgium. RI Feagan, Brian/M-4283-2015 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 849 BP S313 EP S313 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502107 ER PT J AU Sandborn, WJ Colombel, JF Reinisch, W Feagan, BG Rachmilewitz, D Olson, A Johanns, J Travers, S Present, D Sands, BE Hanauer, SB Lichenstein, GR de Villiers, WJS Rutgeerts, P AF Sandborn, WJ Colombel, JF Reinisch, W Feagan, BG Rachmilewitz, D Olson, A Johanns, J Travers, S Present, D Sands, BE Hanauer, SB Lichenstein, GR de Villiers, WJS Rutgeerts, P TI Infliximab induces and maintains mucosal healing in ulcerative colitis patients: The ACT trials SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Katholieke Univ Leuven Hosp, Louvain, Belgium. CHU Lelle, Hosp Claude Huriez, Lille, France. Univ Hosp Vienna, Vienna, Austria. Univ Western Ontario, Robarts Res Inst, London, ON N6A 3K7, Canada. Shaare Zadek Med Ctr, Dept Med, Jerusalem, Israel. Centocor Inc, Clin Res & Dev, Malvern, PA 19355 USA. Centocor Inc, Biostat, Malvern, PA 19355 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Univ Kentucky, Dept Med, Lexington, KY 40506 USA. Mayo Clin, Rochester, MN USA. RI Feagan, Brian/M-4283-2015 NR 0 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 841 BP S310 EP S310 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502099 ER PT J AU Sandborn, WJ Lichtenstein, GR Colombel, JF Yan, S Sands, BE Eisenberg, D Olson, A Rutgeerts, PJ AF Sandborn, WJ Lichtenstein, GR Colombel, JF Yan, S Sands, BE Eisenberg, D Olson, A Rutgeerts, PJ TI Infliximab therapy reduces hospitalizations in ulcerative colitis patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Mayo Clin, Rochester, MN USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. CHU Lille, Hosp Claude Huriez, F-59037 Lille, France. Centocor Inc, Outcomes Res, Malvern, PA 19355 USA. Centocor Inc, Clin Res & Dev, Malvern, PA 19355 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 847 BP S312 EP S312 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502105 ER PT J AU Wang, HS Oh, DS Ohning, GV Pisegna, JR AF Wang, HS Oh, DS Ohning, GV Pisegna, JR TI Validation of endoscopic gastric analysis (EGA) as a method to determine gastric acid output performed during a standard esophagogastroduodenoscopy (EGD) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 VA Greater LA Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 966 BP S353 EP S353 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853502223 ER PT J AU Wang, HS Oh, DS Ohning, GV Pisegna, JR AF Wang, HS Oh, DS Ohning, GV Pisegna, JR TI Elevated serum bioactive ghrelin levels in patients with metastatic neuroendocrine tumors maintains body weight SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. VA Greater LA Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2005 VL 100 IS 9 SU S MA 166 BP S78 EP S78 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964BK UT WOS:000231853500167 ER PT J AU Miller, MR Pronovost, P Donithan, M Zeger, S Zhan, CL Morlock, L Meyer, GS AF Miller, MR Pronovost, P Donithan, M Zeger, S Zhan, CL Morlock, L Meyer, GS TI Relationship between performance measurement and accreditation: Implications for quality of care and patient safety SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE safety; quality of health care/statistics and numerical data; medical error; inpatients; hospitals ID HOSPITALS AB This study examined the association between the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) accreditation scores and the Agency for Healthcare Research and Quality's Inpatient Quality Indicators and Patient Safety Indicators (IQIs/PSIs). JCAHO accreditation data from 1997 to 1999 were matched with institutional IQL/PSI performance from 24 states in the Healthcare Cost and Utilization Project. Most institutions scored high on JCAHO measures despite IQL/PSI performance variation with no significant relationship between them. Principal component analysis found 1 factor each of the IQIs/PSIs that explained the majority of variance on the IQIs/PSIs. Worse performance on the PSI factor was associated with worse performance on JCAHO scores (P = .02). No significant relationships existed between JCAHO categorical accreditation decisions and IQL/PSI performance. Few relationships exist between JCAHO scores and IQI/PSI performance. There is a need to continuously reevaluate all measurement tools to ensure they are providing the public with reliable, consistent information about health care quality and safety. C1 Johns Hopkins Univ, Sch Med, Qual & Safety Initiat, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth & Hyg, Baltimore, MD USA. Agcy Healthcare Res & Qual, Ctr Qual Improvement & Patient Safety, Rockville, MD USA. Massachusetts Gen Phys Org, Boston, MA USA. RP Miller, MR (reprint author), Johns Hopkins Childrens Ctr, CMSC 2-125,600 N Wolfe St, Baltimore, MD 21287 USA. EM mmille21@jhmi.edu NR 34 TC 44 Z9 45 U1 19 U2 30 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD SEP-OCT PY 2005 VL 20 IS 5 BP 239 EP 252 DI 10.1177/1062860605277076 PG 14 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 968PF UT WOS:000232173800003 PM 16221832 ER PT J AU Olson, AL Zwillich, C AF Olson, AL Zwillich, C TI The obesity hypoventilation syndrome SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE obesity hypoventilation syndrome; obstructive sleep apnea syndrome; obstructive sleep apnea-hypopnea syndrome; hypercapnia; hypoventilation; Pickwickian syndrome; obesity ID OBSTRUCTIVE SLEEP-APNEA; PICKWICKIAN-SYNDROME; OXYGEN DESATURATION; MORBID-OBESITY; LUNG-DISEASE; WEIGHT-LOSS; LEPTIN; HYPERCAPNIA; VENTILATION; PREVALENCE AB The obesity hypoventilation syndrome, which is defined as a combination of obesity and chronic hypoventilation, utimately results in pulmonary hypertension, cor pulmonale, and probable early mortality. Since the classical description of this syndrome nearly fifty years ago, research has led to a better understanding of the pathophysiologic mechanisms involved in this disease process, and to the development of effective treatment options. However, recent data indicate the obesity hypoventilation syndrome is under-recognized, and under-treated. Because obesity has become a national epidemic, it is critical that physicians are able to recognize and treat obesity-associated diseases. This article reviews current definitions of the obesity hypoventilation syndrome, clinical presentation and diagnosis, present understanding of the pathophysiology, and treatment options. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Olson, AL (reprint author), Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, 4200 E 9th Ave, Denver, CO 80262 USA. EM amy.olson@uchsc.edu NR 69 TC 128 Z9 132 U1 2 U2 12 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 SEP PY 2005 VL 118 IS 9 BP 948 EP 956 DI 10.1016/j.amjmed.2005.03.042 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 963MB UT WOS:000231807300004 PM 16164877 ER PT J AU Mullins, ME Barest, GD Schaefer, PW Hochberg, FH Gonzalez, RG Lev, MH AF Mullins, ME Barest, GD Schaefer, PW Hochberg, FH Gonzalez, RG Lev, MH TI Radiation necrosis versus glioma recurrence: Conventional MR imaging clues to diagnosis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID PROTON/PHOTON IRRADIATION; TUMOR PROGRESSION; BRAIN-TUMORS; RADIONECROSIS; TRIAL; PET AB BACKGROUND AND PURPOSE: Conventional MR imaging findings are considered to be inadequate for reliably distinguishing radiation necrosis from tumor recurrence in patients with glioma. Despite this belief, we hypothesized that certain conventional MR imaging findings, alone or in combination, though not definitive, may favor one or another of these diagnoses in proton beam-treated patients with new enhancing lesions on serial scanning. METHODS: MR imaging findings (axial T1-, T2-, and post-gadolinium T1-weighted) of 27 proton beam radiation therapy patients with high-grade gliomas were retrospectively reviewed. Entry criteria included new MR imaging enhancing lesions after treatment and histologically unequivocal biopsy proof of diagnosis. Readers rated corpus callosum involvement, midline spread, subependymal spread, new discrete multiple enhancing foci, a "spreading wavefront" appearance, and septum pellucidum involvement. Statistical analysis was by the Fisher exact test. RESULTS: Corpus callosum involvement in combination with multiple other findings was highly associated with progressive glioma. These combinations included involvement of the corpus callosum with multiple enhancing foci (P = .02), involvement of the corpus callosum with crossing the midline and multiple enhancing lesions (P = .04), and involvement of the corpus callosum with subependymal spread and multiple enhancing lesions (P = .01). CONCLUSIONS: In proton beam-treated patients with glioma, corpus callosum involvement, in conjunction with multiple enhancing lesions with or without crossing of the midline and subependymal spread, favors predominant glioma progression. Overall, combinations of enhancement patterns were more likely than individual patterns to distinguish necrosis from predominant tumor progression. Together with clinical and functional imaging findings, these results may assist in determining the need for biopsy. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA USA. Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 15 TC 88 Z9 93 U1 1 U2 4 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2005 VL 26 IS 8 BP 1967 EP 1972 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 964RB UT WOS:000231897100017 PM 16155144 ER PT J AU Chang, EY Barbosa, E Paintlia, MK Singh, A Singh, I AF Chang, EY Barbosa, E Paintlia, MK Singh, A Singh, I TI The use of N-acetylcysteine for the prevention of hypertension in the-reduced uterine perfusion pressure model for preeclampsia in Sprague-Dawley rats SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE preeclampsia; animal model; antioxidants; nuclear factor kappa B ID ENDOTHELIAL GROWTH-FACTOR; KAPPA-B; NITRIC-OXIDE; OXIDATIVE STRESS; CELLS; RISK; SUPEROXIDE; INHIBITION; ACTIVATION; WOMEN AB Objective: To determine whether N-acetylcysteine attenuates abnormal changes in the reduced uterine perfusion pressure model. Study design: Twenty-four timed-pregnant Sprague-Dawley rats underwent sham surgery or the reduced uterine perfusion pressure procedure on day 15 of 22. Reduced uterine perfusion pressure animals were treated with N-acetylcysteine (100 mg/kg) or saline twice daily until delivery. On day 21 of 22, mean arterial pressure was determined and maternal tissue was collected and stored. Pups and pup brains were weighed. Statistical analysis was performed using I-way analysis of variance and the Tukey-Kramer test with significance at P<.05. Results: There was a significant increase in blood pressure with the reduced uterine perfusion pressure procedure (P =.016), which was alleviated by N-acetylcysteine (P = .044). There was a significant decrease in pup weight and brain weight with the reduced uterine perfusion pressure procedure (P =.043 and P =.046, respectively). N-acetyleysteine restored pup brain weight (P =.021) but had no significant effect on pup weight. Conclusion: N-acetylcysteine reduced blood pressure without adversely effecting fetal weight. (C) 2005 Mosby, Inc. All rights reserved. C1 Med Univ S Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat & Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Chang, EY (reprint author), Med Univ S Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, 96 Jonathan Lucas St,Suite 634,POB 250619, Charleston, SC 29425 USA. EM changey@musc.edu FU NIAMS NIH HHS [1 P50 ARO49551] NR 25 TC 9 Z9 10 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2005 VL 193 IS 3 BP 952 EP 956 DI 10.1016/j.ajog.2005.05.083 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 966IQ UT WOS:000232013700009 PM 16157093 ER PT J AU Mocan, MC Azar, NF AF Mocan, MC Azar, NF TI Amniotic membrane transplantation for the repair of severe conjunctival dehiscence after strabismus surgery with adjustable sutures SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To evaluate the outcome of amniotic membrane transplantation (A-MT) for the repair of severe conjuctival dehiscence that occurred during or after fornixincision strabismus surgery with adjustable sutures. DESIGN: Retrospective, interventional case series. METHODS: Four patients in whom severe conjunctival dehiscence developed during or after strabismus surgery were treated with amniotic membrane grafts. The extent of conjunctival reepithelization over sclera, range of ocular motility, and patient comfort were evaluated immediately after the surgery and at 1, 2, and 4 weeks. RESULTS: The mean follow,up period was 16 weeks (range 4 to 28 weeks). Conjunctival dehiscence was detected 0 to 14 days after surgery. AMT was performed 0 to 14 days later. The conjunctival defect was reepithelized in all patients by the fourth postoperative week without evidence of scarring or restriction of motility. CONCLUSIONS: In the treatment of large conjunctival defects that may follow strabismus surgery, AMT may be an alternative to conservative management or primary conjunctival closure. (Am J Ophthalmol 2005;140: 533-534. (c) 2005 by Elsevier Inc. All rights reserved). C1 Massachusetts Eye & Ear Infirm, Pediatr Ophthalmol & Strabismus Serv, Boston, MA 02114 USA. RP Azar, NF (reprint author), Massachusetts Eye & Ear Infirm, Pediatr Ophthalmol & Strabismus Serv, Floor 1,243 Charles St, Boston, MA 02114 USA. EM nathatie_azar@meei.harvard.edu NR 4 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2005 VL 140 IS 3 BP 533 EP 534 PG 2 WC Ophthalmology SC Ophthalmology GA 965DC UT WOS:000231929300029 PM 16139008 ER PT J AU Durand, ML Kim, IK D'Amico, DJ Loewenstein, JI Tobin, EH Kieval, SJ Martin, SS Azar, DT Miller, FS Lujan, BJ Miller, JW AF Durand, ML Kim, IK D'Amico, DJ Loewenstein, JI Tobin, EH Kieval, SJ Martin, SS Azar, DT Miller, FS Lujan, BJ Miller, JW TI Successful treatment of Fusarium endophthalmitis with voriconazole and Aspergillus endophthalmitis with voriconazole plus caspofungin SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID FUNGAL ENDOPHTHALMITIS AB PURPOSE: To report successful treatment of exogenous Fusarium and Aspergillus endophthalmitis with new antifungal agents. DESIGN: Interventional case report. METHODS: Treatment of two cases is reviewed. RESULTS: A 64-year-old man developed post-cataract Fusarium, monitiforme endophthalmitis. Infection persisted despite removal of the intraocular lens, three vitrectomies, and five intravitreal injections of amphotericin. Inflammation resolved and vision improved from 20/80 to 20/40 on 6 months of oral voriconazole. A 55,year,old man developed post-cataract intraocular inflammation. After three vitrectomies and removal of the intraocular lens, Aspergillus fumigatus endophthalmlitis was diagnosed. Intravitreal amphotericin and systemic voriconazole were given, but one week later there were early signs of recurrence. Intravenous caspofungin was added and the eye improved. Caspofungin was continued for 6 weeks and voriconazole for 6 months. Vision improved from counting fingers to 20/80 at 6 months and 20/25 at 23 months. CONCLUSION: Voriconazole is a promising new therapy for Fusarium and Aspergillus endophthalmitis. Caspofungin may act synergistically with voriconazole in treating Aspergillus endophthalmitis. (Am J Ophthalmol 2005;140:552-554- (c) 2005 by Elsevier Inc. All rights reserved). C1 Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Albany Med Coll, Albany, NY 12208 USA. Aroostock Med Ctr, Presque Isle, ME USA. Maine Med Ctr, Portland, ME 04102 USA. Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. RP Durand, ML (reprint author), Massachusetts Eye & Ear Infirm, Infect Dis Serv, 243 Charles St, Boston, MA 02114 USA. EM mdurand@partners.org NR 7 TC 42 Z9 48 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2005 VL 140 IS 3 BP 552 EP 554 DI 10.1016/j.ajo.2005.03.030 PG 3 WC Ophthalmology SC Ophthalmology GA 965DC UT WOS:000231929300038 PM 16139017 ER PT J AU Evans, AK Cunningham, MJ AF Evans, AK Cunningham, MJ TI Atypical mycobacterial cervicofacial lymphadenitis in children: a disease as old as mankind, yet a persistent challenge SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID NONTUBERCULOUS MYCOBACTERIA; CERVICAL LYMPHADENITIS; INFECTIONS; NECK; DIAGNOSIS; HEAD AB The diagnosis of atypical cervicofacial lymphadenitis is often not readily clinically apparent. Parents may bring a child to the physician's attention long before the development of the classic findings. When assessing the child with acute-onset cervicofacial lymphadenitis, there are 2 imperative clinical determinations: Is the lymphadenitis of viral, bacterial, or mycobacterial etiology? If of mycobacterial etiology, is it an atypical or tuberculous mycobacterial process? The goal in management is to avoid misdiagnosis and lengthy duration of symptoms before appropriate therapy is instituted. This paper includes a case study-based review of the evaluation, diagnosis, and management of cervicofacial lymphadenitis in children due to atypical mycobacterial organisms. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Div Pediat Otolaryngol, Boston, MA 02114 USA. EM michael_cunningham@meei.harvard.edu NR 19 TC 1 Z9 1 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD SEP-OCT PY 2005 VL 26 IS 5 BP 337 EP 343 DI 10.1016/j.amjoto.2005.01.018 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 970PC UT WOS:000232321100010 PM 16137534 ER PT J AU Huang, W Dobberfuhl, A Filippopoulos, T Ingelsson, M Fileta, JB Poulin, NR Grosskreutz, CL AF Huang, W Dobberfuhl, A Filippopoulos, T Ingelsson, M Fileta, JB Poulin, NR Grosskreutz, CL TI Transcriptional up-regulation and activation of initiating caspases in experimental glaucoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GANGLION-CELL DEATH; UNBIASED STEREOLOGICAL ESTIMATION; LASER-CAPTURE MICRODISSECTION; OPTIC-NERVE TRANSECTION; RAT MODEL; IN-VIVO; APOPTOSIS; EXPRESSION; NUMBER; FRACTIONATOR AB in glaucoma, retinal ganglion cells (RGCs) die by apoptosis, generally attributed to an elevated intraocular pressure (IOP). We now describe the impact of elevated IOP in the rat on expression of caspase 8 and caspase 9, initiators of the extrinsic and intrinsic caspase cascades, respectively. Activation of both caspases was demonstrated by the presence of cleaved forms of the caspases and the detection of cleaved Bid and PARP, downstream consequences of caspase activation. Surprisingly, the absolute level of procaspase 9 was also elevated after 10 days of increased IOP. To examine the cause of increased levels of the procaspase, we used laser capture microdissection to capture Fluorogold back-labeled RGCs and real-time polymerase chain reaction to measure mRNA changes of initiating caspases. The mRNA levels of both caspase 8 and caspase 9 were increased specifically in RGCs. These data suggest that elevated IOP activates a transcriptional up-regulation and activation of initiating caspases in RGCs and triggers apoptosis through both extrinsic and intrinsic caspase cascades. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu FU NEI NIH HHS [EY14104, P30 EY014104, EY13399, R01 EY013399] NR 28 TC 44 Z9 44 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2005 VL 167 IS 3 BP 673 EP 681 DI 10.1016/S0002-9440(10)62042-1 PG 9 WC Pathology SC Pathology GA 959JR UT WOS:000231514500005 PM 16127148 ER PT J AU Bruel, BM Dajoyag-Mejia, MA AF Bruel, BM Dajoyag-Mejia, MA TI Shoulder mass and pain in a patient with C5 American Spinal Injury Association grade A tetraplegia SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Editorial Material ID DESMOID TUMOR C1 Michael E Debakey Vet Affairs Med Ctr, Spinal Cord Injury Care Line, Houston, TX 77030 USA. Univ Texas, Baylor Coll Med, Houston Med Sch Phys Med & Rehabil Alliance, Houston, TX USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Dajoyag-Mejia, MA (reprint author), Michael E Debakey Vet Affairs Med Ctr, Spinal Cord Injury Care Line, 2002 Holcombe Blvd 128, Houston, TX 77030 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP PY 2005 VL 84 IS 9 BP 725 EP 725 DI 10.1097/01.phm.0000176417.96898.79 PG 1 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 962XS UT WOS:000231767300013 PM 16141754 ER PT J AU Misra, M Miller, KK Kuo, K Griffin, K Stewart, V Hunter, E Herzog, DB Klibanski, A AF Misra, M Miller, KK Kuo, K Griffin, K Stewart, V Hunter, E Herzog, DB Klibanski, A TI Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hormone; cortisol; insulin resistance; estradiol; ghrelin; thyroid hormones ID GROWTH-HORMONE TREATMENT; SERUM LEPTIN; BODY-COMPOSITION; PLASMA-LEVELS; INSULIN SENSITIVITY; NONACYLATED GHRELIN; ACYLATED GHRELIN; BONE METABOLISM; OBESE GENE; WOMEN AB Leptin, an adipocytokine that suppresses appetite and may regulate neuroendocrine pathways, is low in undernourished states like anorexia nervosa ( AN). Although leptin exhibits pulsatility, secretory characteristics have not been well described in adolescents and in AN, and the contribution of hypoleptinemia to increased growth hormone ( GH) and cortisol in AN has not been explored. We hypothesized that hypoleptinemia in AN reflects decreased basal and pulsatile secretion and may predict increased GH and cortisol levels. Sampling for leptin, GH, cortisol, and ghrelin was performed every 30 min ( from 2000 to 0800) in 23 AN and 21 controls 12 - 18 yr old, and data were analyzed using Cluster and deconvolution methods. Estradiol, thyroid hormones, and body composition were measured. AN girls had lower pulsatile and total leptin secretion than controls ( P < 0.0001) subsequent to decreased burst mass ( P < 0.0001) and basal secretion ( P = 0.02). Nutritional markers predicted leptin characteristics. In a regression model including BMI, body fat, and ghrelin, leptin independently predicted GH burst interval and frequency. Valley leptin contributed to 56% of the variability in GH burst interval, and basal leptin and fasting ghrelin contributed to 42% of variability in burst frequency. Pulsatile leptin independently predicted urine free cortisol/ creatinine ( 15% of variability). Valley leptin predicted cortisol half- life ( 22% of variability). Leptin predicted estradiol and thyroid hormone levels. In conclusion, hypoleptinemia in AN is subsequent to decreased basal and pulsatile secretion and nutritionally regulated. Leptin predicts GH and cortisol parameters and with ghrelin predicts GH burst frequency. Low leptin and high ghrelin may be dual stimuli for high GH concentrations in undernutrition. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org RI Griffin, Kathryn/K-1677-2016 OI Griffin, Kathryn/0000-0002-3154-3273 FU NCRR NIH HHS [K23 RR-018851, M01 RR-01066]; NIDDK NIH HHS [DK-062249] NR 45 TC 58 Z9 58 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 SEP PY 2005 VL 289 IS 3 BP E373 EP E381 DI 10.1152/ajpendo.00041.2005 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 957SZ UT WOS:000231394900005 PM 15811876 ER PT J AU Baker, FC Angara, C Szymusiak, R McGinty, D AF Baker, FC Angara, C Szymusiak, R McGinty, D TI Persistence of sleep-temperature coupling after suprachiasmatic nuclei lesions in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE brain temperature; ambient temperature; rapid eye movement sleep; slow wave activity ID CIRCADIAN-RHYTHMS; BODY-TEMPERATURE; REM-SLEEP; RECOVERY SLEEP; DEPRIVATION; WAKEFULNESS; HOMEOSTASIS; RESPONSES; HAMSTERS; SYSTEM AB The suprachiasmatic nucleus (SCN) regulates the circadian rhythms of body temperature (T-b) and vigilance states in mammals. We studied rats in which circadian rhythmicity was abolished after SCN lesions (SCNx rats) to investigate the association between the ultradian rhythms of sleep-wake states and brain temperature (T-br), which are exposed after lesions. Ultradian rhythms of T-br (mean period: 3.6 h) and sleep were closely associated in SCNx rats. Within each ultradian cycle, nonrapid eye movement (NREM) sleep was initiated 5 +/- 1 min after T-br peaks, after which temperature continued a slow decline (0.02 +/- 0.006 degrees C/min) until it reached a minimum. Sleep and slow wave activity (SWA), an index of sleep intensity, were associated with declining temperature. Cross-correlation analysis revealed that the rhythm of T-br preceded that of SWA by 2-10 min. We also investigated the thermoregulatory and sleep-wake responses of SCNx rats and controls to mild ambient cooling (18 degrees C) and warming (30 degrees C) over 24-h periods. SCNx rats and controls responded similarly to changes in ambient temperature. Cooling decreased REM sleep and increased wake. Warming increased T-br, blunted the amplitude of ultradian T-br rhythms, and increased the number of transitions into NREM sleep. SCNx rats and controls had similar percentages of NREM sleep, REM sleep, and wake, as well as the same average T-b within each 24-h period. Our results suggest that, in rats, the SCN modulates the timing but not the amount of sleep or the homeostatic control of sleep-wake states or T-b during deviations in ambient temperature. C1 VA Grester Los Angeles Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Univ Witwatersrand, Sch Physiol, Brain Funct Res Unit, Johannesburg, South Africa. RP McGinty, D (reprint author), VA Grester Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NIMH NIH HHS [MH 47480, MH 004708] NR 45 TC 16 Z9 16 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2005 VL 289 IS 3 BP R827 EP R838 DI 10.1152/ajpregu.00093.2005 PG 12 WC Physiology SC Physiology GA 955RC UT WOS:000231243700025 PM 15860650 ER PT J AU Johansen, KL Doyle, J Sakkas, GK Kent-Braun, JA AF Johansen, KL Doyle, J Sakkas, GK Kent-Braun, JA TI Neural and metabolic mechanisms of excessive muscle fatigue in maintenance hemodialysis patients SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE oxidative phosphorylation; central fatigue; electromyography; muscle activation; P-31 magnetic resonance spectroscopy ID HUMAN SKELETAL-MUSCLE; CHRONIC-RENAL-FAILURE; PERIPHERAL ARTERIAL-DISEASE; VOLUNTARY CONTRACTIONS; OXIDATIVE-METABOLISM; EXERCISE CAPACITY; MUSCULAR FATIGUE; SEX-DIFFERENCES; ERYTHROPOIETIN; ACTIVATION AB Dialysis patients have severe exercise limitations related to metabolic disturbances, but muscle fatigue has not been well studied in this population. We investigated the magnitude and mechanisms of fatigue of the ankle dorsiflexor muscles in patients on maintenance hemodialysis. Thirty-three dialysis patients and twelve healthy control subjects performed incremental isometric dorsiflexion exercise, beginning at 10% of their maximal voluntary contraction (MVC) and increasing by 10% every 2 min. Muscle fatigue (fall of MVC), completeness of voluntary activation, and metabolic responses to exercise were measured. Before exercise, dialysis subjects exhibited reduced strength and impaired peripheral activation (lower compound muscle activation potential amplitude) but no metabolic perturbation. During exercise, dialysis subjects demonstrated threefold greater fatigue than controls with evidence of central activation failure but no change in peripheral activation. All metabolic parameters were significantly more perturbed at end exercise in dialysis subjects than in controls, including lower phosphocreatine (PCr) and pH, and higher P-i, P-i/PCr, and H2PO4-. Oxidative potential was markedly lower in patients than in controls [62.5 (SD 27.2) vs. 134.6 ( SD 31.7), P < 0.0001]. Muscle fatigue was negatively correlated with oxidative potential among dialysis subjects (r = -0.52, P = 0.04) but not controls. Changes in central activation ratio were also correlated with muscle fatigue in the dialysis subjects (r = 0.59, P = 0.001) but not the controls. This study provides new information regarding the excessive muscular fatigue of dialysis patients and demonstrates that the mechanisms of this fatigue include both intramuscular energy metabolism and central activation failure. C1 San Francisco Vet Affairs Med Ctr, Dialysis Unit, Nephrol Sect, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. No Calif Inst Res & Educ, San Francisco, CA USA. Univ Massachusetts, Dept Exercise Sci, Amherst, MA 01003 USA. RP Johansen, KL (reprint author), San Francisco Vet Affairs Med Ctr, Dialysis Unit, Nephrol Sect, Dept Med, 4150 Clement St, San Francisco, CA 94121 USA. EM johanse@itsa.ucsf.edu FU NCRR NIH HHS [RR 00083]; NIDDK NIH HHS [R01 DK 56182] NR 56 TC 37 Z9 42 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2005 VL 289 IS 3 BP R805 EP R813 DI 10.1152/ajpregu.00187.2005 PG 9 WC Physiology SC Physiology GA 955RC UT WOS:000231243700023 PM 15905222 ER PT J AU Hudziak, JJ Derks, EM Althoff, RR Rettew, DC Boomsma, DI AF Hudziak, JJ Derks, EM Althoff, RR Rettew, DC Boomsma, DI TI The genetic and environmental contributions to attention deficit hyperactivity disorder as measured by the Conners' Rating Scales - Revised SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CHILD-BEHAVIOR CHECKLIST; TWINS; ADHD; HERITABILITY AB Objective: The majority of published reports on twin studies of attention deficit hyperactivity disorder ( ADHD) have indicated robust additive genetic influences and unique environmental influences. These studies typically used DSM ADHD symptoms collected by telephone or interviews with mothers. The purpose of this study was to test the genetic architecture of ADHD by using the ADHD index from Conners' Rating Scales - Revised. Method: From the Conners' scale forms, data for the ADHD index were collected from the mothers of 1,595 7-year-old twin pairs from the Netherlands Twin Registry. Rates of ADHD diagnoses were computed by using Conners' gender- and age-specific cutoff points. Contributions from additive, dominant, unique environmental, interaction, and gender effects were computed by using gender- genetic models. Results: The prevalence of ADHD across the sample of 7-year-old twin pairs was about 4% according to the mothers' reports, consistent with other reported rates of ADHD. However, using the gender norms provided with the ADHD index, the authors found slightly higher rates of ADHD in girls than previously reported. Genetic analyses yielded a model that includes genetic dominance ( 48%), additive genetic factors ( 30%), and unique environmental factors ( 22%). Conclusions: The ADHD index from Conners' Rating Scales - Revised identified an appropriate percentage of children across this epidemiologic twin sample as being at risk for ADHD. The results of the genetic analyses are consistent with prior reports that ADHD is predominantly influenced by genetic factors that are both dominant and additive. C1 Univ Vermont, Dept Psychiat, Div Behav Genet, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Vrije Univ Amsterdam, Fac Psychol & Educ, NL-1081 HV Amsterdam, Netherlands. RP Hudziak, JJ (reprint author), Univ Vermont, Dept Psychiat, Div Behav Genet, Given B229, Burlington, VT 05405 USA. EM jhudziak@zoo.uvm.edu RI Derks, Eske/A-1652-2017 OI Derks, Eske/0000-0002-6292-6883 FU NIMH NIH HHS [MH-58799] NR 18 TC 57 Z9 60 U1 1 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2005 VL 162 IS 9 BP 1614 EP 1620 DI 10.1176/appi.ajp.162.9.1614 PG 7 WC Psychiatry SC Psychiatry GA 959ZT UT WOS:000231559300007 PM 16135619 ER PT J AU Kaur, S Sassi, RB Axelson, D Nicoletti, M Brambilla, P Monkul, ES Hatch, JP Keshavan, MS Ryan, N Birmaher, B Soares, JC AF Kaur, S Sassi, RB Axelson, D Nicoletti, M Brambilla, P Monkul, ES Hatch, JP Keshavan, MS Ryan, N Birmaher, B Soares, JC TI Cingulate cortex anatomical abnormalities in children and adolescents with bipolar disorder SO AMERICAN JOURNAL OF 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 ID POSITRON-EMISSION-TOMOGRAPHY; SUBGENUAL PREFRONTAL CORTEX; ANTERIOR CINGULATE; MOOD DISORDERS; VOLUME ASYMMETRIES; SCHIZOPHRENIA; RESONANCE; DEPRESSION; BRAIN; MANIA AB Objective: In vivo imaging studies have suggested anatomical and functional abnormalities in the anterior cingulate in adults with mood disorders. This anatomical magnetic resonance imaging study examined the cingulate cortex in children and adolescents with bipolar disorder and matched healthy comparison subjects. Method: Sixteen patients ( mean age= 15.5 years, SD= 3.4) with DSM-IV bipolar disorder and 21 matched healthy comparison subjects ( mean age= 16.9 years, SD= 3.8) were studied. Three-dimensional gradient echo imaging was performed ( TR= 25 msec, TE= 5 msec, slice thickness= 1.5 mm) in a 1.5-n T GE Signa magnet. Cingulate volumes were compared by using analysis of covariance, with age and intracranial volume as covariates. Results: The patients with bipolar disorder had significantly smaller mean volumes relative to the healthy subjects in the left anterior cingulate ( mean= 2.49 cm(3) [ SD= 0.28] versus 3.60 cm(3) [ SD= 0.12], respectively), left posterior cingulate ( 2.53 cm(3) [ SD= 0.32] versus 2.89 cm(3) [ SD= 0.09]), and right posterior cingulate ( 2.19 cm3 [ SD= 0.13] versus 2.28 cm(3) [ SD= 0.08]). No significant between-group difference was found for the right anterior cingulate ( 2.64 cm3 [ SD= 0.21] versus 2.71 cm(3) [ SD= 0.10]). Conclusions: The findings indicate smaller cingulate volumes in children and adolescents with bipolar disorder, suggesting that such abnormalities may be present early in the illness course. C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. 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-01736, MH-30915, MH-55123, MH-59929] NR 43 TC 75 Z9 75 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2005 VL 162 IS 9 BP 1637 EP 1643 DI 10.1176/appi.ajp.162.9.1637 PG 7 WC Psychiatry SC Psychiatry GA 959ZT UT WOS:000231559300010 PM 16135622 ER PT J AU Pai, M Lewinsohn, DM AF Pai, M Lewinsohn, DM TI Interferon-gamma assays for tuberculosis - Is anergy the Achilles' heel? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID INFECTION; ANTIGENS; CHILDREN; HIV C1 Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94143 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Pai, M (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94143 USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 14 TC 46 Z9 47 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 SEP 1 PY 2005 VL 172 IS 5 BP 519 EP 521 DI 10.1164/rccm.2506003 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 960FB UT WOS:000231574500003 PM 16120714 ER PT J AU Borczuk, R Kandiah, PA Resnick, JB Nagurney, JT Koroshetz, WJ Furie, KL Gonzalez, RG Lev, M Singhal, AB AF Borczuk, R Kandiah, PA Resnick, JB Nagurney, JT Koroshetz, WJ Furie, KL Gonzalez, RG Lev, M Singhal, AB TI Emergency department utilization of magnetic resonance imaging in patients with acute neurologic conditions SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S63 EP S64 PG 2 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000227 ER PT J AU Boudreaux, ED Clark, S Hugli, OW Camargo, CA AF Boudreaux, ED Clark, S Hugli, OW Camargo, CA TI Multicenter study of smoking, depression, and suicidal ideation among emergency department patients SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 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 SEP PY 2005 VL 46 IS 3 SU S BP S99 EP S99 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000356 ER PT J AU Camargo, CA Clark, S AF Camargo, CA Clark, S TI Chronic asthma severity among children presenting to the emergency department with asthma exacerbations SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S101 EP S102 PG 2 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000364 ER PT J AU Clark, S Pelletier, AJ Brenner, BE Lang, DM Strunk, RC Camargo, CA AF Clark, S Pelletier, AJ Brenner, BE Lang, DM Strunk, RC Camargo, CA TI Feasibility of a national fatal asthma registry: More evidence of institutional review board variation in evaluation of a standard protocol SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cleveland Clin, Cleveland, OH 44106 USA. Washington Univ, Med Ctr, Childrens Hosp, St Louis, MO 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S102 EP S102 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000367 ER PT J AU Filbin, M Bisanzo, M Mezrich, J Thomas, SH AF Filbin, M Bisanzo, M Mezrich, J Thomas, SH TI Mortality of hypotensive patients with sepsis in the emergency department compared with hypotensive patients of other etiologies SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S75 EP S75 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000267 ER PT J AU Goldstein, JN Camargo, CA Edlow, JA AF Goldstein, JN Camargo, CA Edlow, JA TI Headache evaluation in United States emergency departments: Frequency of neurolmaging and diagnostic yield SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Goldstein, Joshua/H-8953-2016 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S72 EP S72 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000257 ER PT J AU Kabrhel, C Matts, C McNamara, M Katz, J AF Kabrhel, C Matts, C McNamara, M Katz, J TI The introduction of a rapid ELISA D-dimer increases emergency department testing with no effect on the diagnosis of pulmonary embolism SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Illinois, Sch Med, Chicago, IL 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S11 EP S11 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000035 ER PT J AU Macias, WL Nentwich, L Hong, C Chan, K Pliakas, J Thomas, SH AF Macias, WL Nentwich, L Hong, C Chan, K Pliakas, J Thomas, SH TI Acute ischemic stroke in the modern era: Impact of stroke care regionalization on evaluation, documentation and patient transport - The Massachusetts general hospital experience SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Wellesley Coll, Wellesley, MA 02181 USA. Boston MedFlight, Bedford, MA 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S62 EP S62 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000220 ER PT J AU Nagurney, JT Resnick, JB Gatha, N Binder, W Filbin, M Borczuk, P Brown, DF Swap, C Parry, B Chang, Y AF Nagurney, JT Resnick, JB Gatha, N Binder, W Filbin, M Borczuk, P Brown, DF Swap, C Parry, B Chang, Y TI Emergency physicians and the neurologic examination SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Affiliated Emergency Med Residency, Boston, MA USA. Albany Med Coll, Albany, NY 12208 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S88 EP S88 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000314 ER PT J AU Radeos, MS Gonzales, R Camargo, CA Maselli, J Metlay, JP AF Radeos, MS Gonzales, R Camargo, CA Maselli, J Metlay, JP TI Is ED testing for group a Streptococcus associated with antibiotic prescription rates for adults with pharyngitis? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Lincoln Med & Mental Hlth Ctr, Bronx, NY 10451 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S16 EP S16 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000051 ER PT J AU Strehlow, MC Emond, SD Pelletier, AJ Camargo, CA AF Strehlow, MC Emond, SD Pelletier, AJ Camargo, CA TI Characteristics and admission patterns of patients presenting with sepsis to United States emergency departments, 1992-2001 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Kaiser Permanente, Santa Clara, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S48 EP S48 PG 1 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000170 ER PT J AU Sutingco, AD Noble, V AF Sutingco, AD Noble, V TI Proctored ultrasound examinations (PUE) significantly improve success in emergency medicine ultrasound education SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT American-College-Emergency-Physicians-Research Forum CY SEP 26-27, 2005 CL Washington, DC SP Amer Coll Emergency Phys Res C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2005 VL 46 IS 3 SU S BP S79 EP S80 PG 2 WC Emergency Medicine SC Emergency Medicine GA 962OB UT WOS:000231741000285 ER PT J AU Greenberg, SM Rosand, J AF Greenberg, SM Rosand, J TI The phosphodiesterase puzzlebox: PDE4D and stroke SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ISCHEMIC-STROKE; RISK; GENE; POPULATION C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. NR 14 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2005 VL 58 IS 3 BP 345 EP 346 DI 10.1002/ana.20623 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961RJ UT WOS:000231679200001 PM 16130101 ER PT J AU Rosand, J Muzikansky, A Kumar, A Wisco, JJ Smith, EE Betensky, RA Greenberg, SM AF Rosand, J Muzikansky, A Kumar, A Wisco, JJ Smith, EE Betensky, RA Greenberg, SM TI Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy SO ANNALS OF NEUROLOGY LA English DT Article ID INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE; LOBAR HEMORRHAGE; MRI; DIAGNOSIS; BETA AB Cerebral amyloid angiopathy (CAA) is a common cause of symptomatic intracerebral hemorrhage (ICH), as well as small asymptomatic hemorrhage in the elderly. We used gradient-echo MRI to analyze spatial distribution of 321 hemorrhages in 59 patients with probable CAA-related ICH. Hemorrhagic lesions were found preferentially in the temporal (ratio of actual to expected hemorrhages = 1.37) and occipital lobes (ratio = 1.45, p < 0.0001). Within individuals, hemorrhages tended to duster, regardless of lobe (p < 0.0001). Among subjects followed prospectively for recurrence, clustering of new symptomatic and asymptomatic hemorrhages was observed. These data suggest that regional differences within the brain play a role in the development of CAA-related hemorrhage. C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH, MIT,Dept Radiol, HMS,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, 15 Parkman St,WACC 836, Boston, MA 02114 USA. EM jrosand@partners.org OI Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [1 K23 NS42695-01, R01 NS041409-01] NR 19 TC 103 Z9 104 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2005 VL 58 IS 3 BP 459 EP 462 DI 10.1002/ana.20596 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 961RJ UT WOS:000231679200016 PM 16130107 ER PT J AU Burns, JA Zeitels, SM Anderson, RR Kobler, JB Pierce, MC de Boer, JF AF Burns, JA Zeitels, SM Anderson, RR Kobler, JB Pierce, MC de Boer, JF TI Imaging the mucosa of the human vocal fold with optical coherence tomography SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY APR 30-MAY 01, 2004 CL Phoenix, AZ SP Amer Laryngol Assoc DE glottis; imaging technique; larynx; optical coherence tomography; vocal fold ID FEASIBILITY; BIREFRINGENCE; TISSUE AB Objectives: Discerning the layered microstructure of the vocal folds is critical for effective phonomicrosurgery. Optical coherence tomography (OCT), a noncontact, noninvasive technology that provides cross-sectional images by means of backscattered light, offers the potential for delineating these layers in vivo. Methods: The glottal mucosa of 3 human cadaver larynges was imaged with conventional OCT and polarization-sensitive OCT (PS-OCT). Images were obtained through the epithelium and lamina propria. Results: Although the superficial layer of the lamina propria appeared quite homogeneous, the outer surface of the superficial lamina propria was correlated with an increase in backscatter with OCT. The superficial lamina propria and vocal ligament were correlated with a marked increase in tissue birefringence with PS-OCT. Conclusions: This preliminary study demonstrates the capacity of OCT and PS-OCT for visualizing the layered microstructure of the vocal fold mucosa. We believe that these imaging techniques will have applications in the exploration of solutions to vocal fold scarring and in imaging vocal fold disorders in the clinic and operating room. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rahabil, Boston, MA 02114 USA. RP de Boer, JF (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 50 Blossom St,Bar 724, Boston, MA 02114 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 26 TC 29 Z9 31 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2005 VL 114 IS 9 BP 671 EP 676 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 964NN UT WOS:000231887900003 PM 16240928 ER PT J AU Khuri, SF Henderson, WG DePalma, RG Mosca, C Healey, NA Kumbhani, DJ AF Khuri, SF Henderson, WG DePalma, RG Mosca, C Healey, NA Kumbhani, DJ CA VA Natl Surgical Quality Improvmen TI Determinants of long-term survival after major surgery and the adverse effect of postoperative complications SO ANNALS OF SURGERY LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; ABDOMINAL AORTIC-ANEURYSM; OF-VETERANS-AFFAIRS; INFLAMMATORY RESPONSE SYNDROME; SURGICAL CARE; RISK-FACTORS; CAROTID-ENDARTERECTOMY; MYOCARDIAL-INFARCTION; OPERATIVE MORTALITY; MEDICAL-CENTERS AB Objective: The objective of this study was to identify the determinants of 30-day postoperative mortality and long-term survival after major surgery as exemplified by 8 common operations. Summary Background Data: The National Surgical Quality Improvement Program (NSQIP) database contains pre-, intra-, and 30-day postoperative data, prospectively collected in a standardized fashion by a dedicated nurse reviewer, on major surgery in the Veterans Administration (VA). The Beneficiary Identification and Records Locator Subsystem (BIRLS) is a VA file that depicts the vital status of U.S. veterans with 87% to 95% accuracy. Methods: NSQIP data were merged with BIRLS to determine the vital status of 105,951 patients who underwent 8 types of operations performed between 1991 and 1999, providing an average follow up of 8 years. Logistic and Cox regression analyses were performed to identify the predictors of 30-day mortality and long-term survival, respectively. Results: The most important determinant of decreased postoperative survival was the occurrence, within 30 days postoperatively, of any one of 22 types of complications collected in the NSQIP. Independent of preoperative patient risk, the occurrence of a 30-day complication in the total patient group reduced median patient survival by 69%. The adverse effect of a complication on patient survival was also influenced by the operation type and was sustained even when patients who did not survive for 30 days were excluded from the analyses. Conclusions: The occurrence of a 30-day postoperative complication is more important than preoperative patient risk and intraoperative factors in determining the survival after major surgery in the VA. Quality and process improvement in surgery should be directed toward the prevention of postoperative complications. C1 VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Colorado, Dept Surg, Hlth Outcomes Program, Aurora, CO USA. VA Cent Off, Patient Care Serv, Washington, DC USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM shukri.khuri@med.va.gov NR 50 TC 467 Z9 477 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2005 VL 242 IS 3 BP 326 EP 343 DI 10.1097/01.sla.0000179621.33268.83 PG 18 WC Surgery SC Surgery GA 962QV UT WOS:000231748200004 PM 16135919 ER PT J AU Tseng, JF Warshaw, AL Sahani, DV Lauwers, GY Rattner, DW Castillo, CF AF Tseng, JF Warshaw, AL Sahani, DV Lauwers, GY Rattner, DW Castillo, CF TI Serous cystadenoma of the pancreas - Tumor growth rates and recommendations for treatment SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 125th Annual Meeting of the American-Surgical-Association CY APR 14-16, 2005 CL Palm Beach, FL SP Amer Surg Assoc ID CYSTIC NEOPLASMS; PATHOLOGICAL OBSERVATIONS; ENDOSCOPIC ULTRASOUND; DIAGNOSIS; CYSTADENOCARCINOMA; MALIGNANCY; MANAGEMENT; ACCURACY; SPECTRUM; ADENOMA AB Objective: To define the natural history and optimal management of serous cystadenoma of the pancreas. Summary Background Data: Serous cystadenoma of the pancreas is the most common benign pancreatic neoplasm. Diagnostic criteria, potential for growth or malignancy, and outcomes are not well defined. As a result, management for patients with serous cystadenomas varies widely in current practice. Methods: A total of 106 patients presenting with serous cystadenoma of the pancreas from 1976-2004 were identified. Hospital records were evaluated for patient and tumor characteristics, diagnostic workup, treatment, and outcome. Twenty-four patients with serial radiographic imaging were identified, and tumor growth curves calculated. Results: Mean age at presentation was 61.5 years and 75% of patients were female. The most common symptoms were abdominal pain (25%), fullness/mass (10%), and jaundice (7%); 47% were asymptomatic. Mean tumor diameter was 4.9 +/- 3.1 cm, which did not vary by location. Tumors < 4 cm were less likely to be symptomatic than were tumors >= 4 cm (22% vs. 72%, P < 0.001). The median growth rate in the patients who had serial radiography was 0.60 cm/y. For tumors < 4 cm at presentation (n = 15), the rate was 0.12 cm/y, whereas for tumors >= 4 cm (n = 9), the rate was 1.98 cm/y (P = 0.0002). Overall, 86 patients underwent surgery, with one perioperative death. Conclusions: Large (> 4 cm) serous cystadenomas are more likely to be symptomatic. Although the median growth rate for this neoplasm is only 0.6 cm/y, it is significantly greater in large tumors. Whereas expectant management is reasonable in small asymptomatic tumors, we recommend resection for large serous cystadenomas regardless of the presence or absence of symptoms. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Castillo, CF (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM cfernandez@partners.org NR 39 TC 168 Z9 185 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2005 VL 242 IS 3 BP 413 EP 421 DI 10.1097/01.sla.0000179651.21193.2c PG 9 WC Surgery SC Surgery GA 962QV UT WOS:000231748200012 PM 16135927 ER PT J AU Gold, JP Begg, WB Fullerton, DA Mathisen, DJ Orringer, MB Verrier, ED AF Gold, JP Begg, WB Fullerton, DA Mathisen, DJ Orringer, MB Verrier, ED TI Evaluation of web-based learning tools: Lessons learned from the Thoracic Surgery Directors Association curriculum project three-year experience SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-26, 2005 CL Tampa, FL SP Soc Thorac Surg ID CONTINUING MEDICAL-EDUCATION; CD-ROM; KNOWLEDGE; PROGRAM; ONLINE; SKILLS AB Background. In 2001 the Thoracic Surgery Directors Association implemented a web-based curriculum for prematriculated TS residents containing 75 learning modules organized into 13 sections Each module contains an audio/video presentation, a summary, frequently asked questions, references, a self-assessment, and a critique. Curriculum content was provided as a randomized prospective trial one year prior to matriculation to residents matching into a TS program from 2001 to 2004. Methods. Over 3 years the utilization and impact of this curriculum was evaluated by 8 different methods including resident surveys, faculty surveys, web tracking, examination scores, and individual online learning module critiques. Each completed critique evaluated the resident's perception of the relevance, content quality and presentation quality of the module on a scale corresponding to low, average and high. Results. A total of 11,117 learning modules were used through the end of 2004 with complete critiques available on 1458 (13%). Utilization and measured quality continue to increase over the 3-year interval. The average rating scores for relevance, content and presentation tracked together and were overall rated as good or excellent (92%). There were large variations in utilization and perceived quality by section subject. As the average module rating score improved, the utilization increased and the variability of the rating decreased substantially. Conclusions. Module specific learner evaluation of educational content is one of several important feedback tools for monitoring ongoing curricular development and refinement. These studies, based upon web tracking, demonstrate increasing resident use and strong resident satisfaction. This educational format will hopefully lend itself to many important improvements in web-based Thoracic Surgery education. C1 Albert Einstein Coll Med, Dept Cardiothorac Surg, New York, NY USA. Thorac Surg Directors Assoc, Arlington, VA USA. Univ Colorado, Hlth Sci Ctr, Div Cardiothorac Surg, Denver, CO USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA. Univ Washington, Div Cardiothorac Surg, Seattle, WA 98195 USA. RP Gold, JP (reprint author), Med Univ Ohio, Coll Med, Raymon H Mulford Lib, 3045 Arlington Ave, Toledo, OH 43614 USA. EM jgold@mco.edu NR 40 TC 10 Z9 10 U1 1 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 SEP PY 2005 VL 80 IS 3 BP 802 EP 810 DI 10.1016/j.athoracsur.2005.03.052 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 961TC UT WOS:000231683700006 PM 16122433 ER PT J AU Shahian, DM Torchiana, DF Normand, SLT AF Shahian, DM Torchiana, DF Normand, SLT TI Implementation of a cardiac surgery report card: lessons from the Massachusetts experience SO ANNALS OF THORACIC SURGERY LA English DT Review ID PERFORMANCE; IMPROVE; ISSUES AB Demand is increasing for public accountability in health care. In 2000, the Massachusetts legislature mandated a state report card for cardiac surgery and percutaneous coronary interventions. During the planning and implementation of this report card, a number of observations were made that may prove useful to other states faced with similar mandates. These include the necessity for constructive, nonadversarial collaboration between regulators, clinicians, and statisticians; the advantages of preemptive adoption of The Society of Thoracic Surgeons [STS] National Cardiac Database, preferably before a report card is mandated; the support and resources available to cardiac surgeons through the STS, the National Cardiac Database Committee, and the Duke Clinical Research Institute; the value of a state STS organization; and the importance of media education to facilitate fair and dispassionate press coverage. Some important features of report cards may vary from state to state depending on the legislative mandate, local preferences, and statistical expertise. These include the choice of a statistical model and analytical technique, national versus regional reference population, and whether individual surgeon profiling is required. C1 Caritas St Elizabeths Med Ctr, Dept Surg, Boston, MA 02135 USA. Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Shahian, DM (reprint author), Caritas St Elizabeths Med Ctr, Dept Surg, 736 Cambridge St, Boston, MA 02135 USA. EM david_shahian@cchcs.org NR 9 TC 27 Z9 27 U1 0 U2 2 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 SEP PY 2005 VL 80 IS 3 BP 1146 EP 1150 DI 10.1016/j.athoracsur.2004.10.046 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 961TC UT WOS:000231683700078 PM 16122520 ER PT J AU Phung, TL Hochman, M Mihm, MC AF Phung, TL Hochman, M Mihm, MC TI Current knowledge of the pathogenesis of infantile hemangiomas SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID GLUCOSE-TRANSPORTER; VASCULAR MALFORMATIONS; JUVENILE HEMANGIOMAS; ENDOTHELIAL-CELLS; HUMAN PLACENTA; EXPRESSION; GROWTH; BARRIER; ANGIOGENESIS; INVOLUTION AB Infantile hemangiomas are the most common benign tumor of infancy, occurring shortly after birth in 5% to 10% of white infants.(1,2) Hemangiomas occur in infants of all races but are most common in those who are white. These lesions are preponderant in females compared with males at rates; of 3:1 to 5:1.(3) Many hemangiomas are discrete, well-circumscribed masses present in the head and neck. Some hemangiomas are segmental and diffuse, often involving large areas of the extremities or the head and neck. Chorionic villus sampling at 9 to 12 weeks of gestation has been associated with a 21% increased incidence of hemangiomas in infants.' Most hemangiomas occur sporadically without a hereditary component. However, in a few families, hemangiomas segregate as a highly penetrant, autosomal dominant trait.(5) Gene linkage studies of familial infantile hemangiomas show evidence of linkage to chromosome 5q31-33.(6) C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Facial Surg Ctr, Charleston, SC USA. Massachusetts Gen Hosp, Div Dermatopathol, Dept Pathol, Boston, MA 02114 USA. RP Phung, TL (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave,RN 287, Boston, MA 02115 USA. EM tphung@bidmc.harvard.edu FU NHLBI NIH HHS [T32 HL07893] NR 32 TC 23 Z9 27 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD SEP-OCT PY 2005 VL 7 IS 5 BP 319 EP 321 DI 10.1001/archfaci.7.5.319 PG 3 WC Surgery SC Surgery GA 983HT UT WOS:000233222800008 PM 16172341 ER PT J AU Rickels, K Pollack, MH Feltner, DE Lydiard, RB Zimbroff, DL Bielski, RJ Tobias, K Brock, JD Zornberg, GL Pande, AC AF Rickels, K Pollack, MH Feltner, DE Lydiard, RB Zimbroff, DL Bielski, RJ Tobias, K Brock, JD Zornberg, GL Pande, AC TI Pregabalin for treatment of generalized anxiety disorder - A 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 155th Annual Meeting of the American-Psychiatric-Association CY MAY 18-23, 2002 CL PHILADELPHIA, PA SP Amer Psychiat Assoc ID VENLAFAXINE EXTENDED-RELEASE; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; POSTHERPETIC NEURALGIA; MAJOR DEPRESSION; PARTIAL SEIZURES; REBOUND ANXIETY; DOSE-RESPONSE; DSM-IV; GABAPENTIN AB Background: Pregabalin inhibits release of excess excitatory neuro transmitters, presumably by binding to the alpha(2)-delta subunit protein of widely distributed voltage-dependent calcium channels in the brain and spinal cord. Objective: To assess the anxiolytic efficacy of pregabalin in patients with generalized anxiety disorder. Design: Double-blind, placebo-controlled, active-comparator trial. Patients were randomized to 4 weeks of treatment with pregabalin, 300 mg/d (n = 91), 450 mg/d (n = 90), or 600 mg/d (n = 89); alprazolam, 1.5 mg/d (n = 93); or placebo (n = 9 1). Setting: Psychiatry research and clinic settings Patients: Outpatients meeting the DSM-IV criteria for generalized anxiety disorder, with a baseline Hamilton Anxiety Rating Scale (HAM-A) total score of 20 or greater. Main Outcome Measures: Change from baseline to end point in total HAM-A score in the pregabalin and alprazolam groups compared with the placebo group. The end point response criterion was 50 % or greater reduction in the HAM-A total score. Results: Pregabalin and alprazolam produced a significantly greater reduction in mean SE HAM-A total score at last-observation-carried-forward end point compared with placebo (-8.4 +/- 0.8): pregabalin, 300 mg (-12.2 +/- 0.8, P < .001), 450 mg (-11.0 +/- 0.8, P = .02), and 600 mg (-11.8 +/- 0.8, P = .002), and alprazolam (-10.9 +/- 0.8, P = .02). By week 1 and at last-observation-carried-forward end point, the 3 pregabalin groups and the alprazolain group had significantly (P < .01) improved HAM-A psychic anxiety symptoms compared with the placebo group. Compared with the placebo group, HAM-A somatic anxiety symptoms were also significantly (P < .02) improved by the 300- and 600-mg pregabalin groups, but not by the 450-mg pregabalin (week 1, P = .06; week 4, P = .32) and the alprazolam. groups (week 1, P =.21; week 4, P =. 15). Of the 5 treatment groups, the 300-mg pregabalin group was the only medication group that differed statistically in global improvement at treatment end point not only from the placebo group but also from the alprazolam group. Conclusion: Pregabalin was significantly more efficacious than placebo for the treatment of psychic and somatic symptoms of generalized anxiety disorder and was well tolerated by most study patients. C1 Univ Penn, Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. SE Hlth Consultants LLC, Charleston, SC USA. Pacific Clin Res, San Bernardino, CA USA. Inst Hlth Studies, Okemos, MI USA. Pfizer Inc, New York, NY USA. RP Rickels, K (reprint author), Univ Penn, Med Ctr, Dept Psychiat, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA. EM krickels@mail.med.upenn.edu NR 47 TC 193 Z9 204 U1 6 U2 20 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 SEP PY 2005 VL 62 IS 9 BP 1022 EP 1030 DI 10.1001/archpsyc.62.9.1022 PG 9 WC Psychiatry SC Psychiatry GA 961RU UT WOS:000231680300010 PM 16143734 ER PT J AU Nayak, VK Deschler, DG AF Nayak, VK Deschler, DG TI Clopidogrel use for reducing the rate of thrombosis in a rat model of microarterial anastomosis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Fall Meeting of the American-Academy-of-Facial-Plastic-and-Reconstructive-Surgery CY SEP 21, 2004 CL New York, NY SP Amer Acad Facial Plast & Reconstruct Surg ID NECK RECONSTRUCTION; HEAD; EXPERIENCE AB Objectives: The national success rate for microvascular free tissue transfer is around 94%. However, in cases of failure, which is most often due to thrombosis in the vascular pedicle, the morbidity can be significant. Microvascular surgeons have used various pharmacologic agents to reduce thrombosis rates; however, none have been ideal. We examined the effects of clopiclogrel bisulfate (Plavix), a member of the relatively new class of antiplatelet agents, on the rate of arterial thrombosis in a rat model. Design: Prospective randomized, blinded. Setting: Tertiary care academic medical center. Subjects: Male Sprague-Dawley rats weighing between 350 and 400 g. Intervention: Clopidogrel or placebo via gavage. After waiting 2 hours for absorption and activation, the "tuck" model of microvascular anastomosis was performed on both femoral arteries. Arteries were transected after 3 hours and patency was assessed. Main Outcome Measures: Bleeding time was obtained by determining the time to clot after removal of 2 mm from the tail tip. Vessel patency was assessed after 3 hours in the clopidogrel-treated and control groups. Results: Of 33 arteries, 19 (58%) in the control group developed complete thrombosis by the end of the period compared with only 6 (19%) of 32 arteries in the group that received clopidogrel. chi(2) Analysis revealed this to be significant (P = .001). The mean (SD) bleeding time in the control group was 158 (44) seconds compared with 233 (48) seconds in the clopidogrel group. Conclusions: Clopidogrel significantly reduced the rate of arterial thrombosis in a rat model of microvascular repair. The average bleeding time in the clopidogrel group was prolonged, suggesting that absorption and activation occurred. These preliminary data suggest a potential role for clopidogrel in select high-risk patients undergoing microvascular free tissue transfer. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Head & Neck Surg, Boston, MA USA. RP Deschler, DG (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_deschler@meei.harvard.edu NR 14 TC 8 Z9 8 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD SEP PY 2005 VL 131 IS 9 BP 800 EP 803 DI 10.1001/archotol.131.9.800 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 962WG UT WOS:000231763300010 PM 16172359 ER PT J AU Renshaw, AA Mody, DR Wang, E Wilbur, DC Colgan, TJ AF Renshaw, AA Mody, DR Wang, E Wilbur, DC Colgan, TJ CA Cytopathology Resource Comm TI Measuring the significance of participant evaluation of acceptability of cases in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROFICIENCY TESTING PROGRAM; ONTARIO; CANADA AB Context.-The quality of gynecologic cytology slides within educational and proficiency testing programs may deteriorate during use. Participant evaluation of the acceptability of these slides subsequent to possible deterioration is not known. Objective.-To assess participants' evaluation of the acceptability of slides circulating within an educational gynecologic cytology glass slide program. Design.-The College of American Pathologists Inter laboratory Comparison Program in Cervicovaginal Cytology is a peer comparison and educational program that evaluates the ability of the participants to correctly classify gynecologic cytology preparations. The program uses both expert review and field validation to select slides for the graded portion of the program. Participants were asked to assess the acceptability of slides within the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology, and their responses were assessed with respect to type of slide preparation, validation status, and reference diagnosis. In addition, we compared the cytodiagnostic discordancy rates of slides that were deemed acceptable by participants with those that were deemed unacceptable. Setting-Participant assessments were derived from pa-thologists and cytotechnologists from cytology laboratories of all types. Results.-A total of 17210 slide interpretations were reviewed, and 2.91 % of the cases were labeled unacceptable by participants. For all slides, the percentage of cases called unacceptable varied from 1.65% for cases with a reference interpretation of herpes to 45% for cases with a reference interpretation of unsatisfactory. The percentage of slides deemed unacceptable was higher for validated slides than for educational slides (3.27% vs 2.55%, P =.006). The discordancy rate (to reference diagnosis series) for cases deemed unacceptable was significantly higher than the discordancy rate for cases deemed acceptable for both validated (10.39% vs 1.76%) and educational slides (21.72% vs 3.53%, P <.001). Conclusion.-Greater than 97% of all slides in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology were judged acceptable by participants. Despite expert review and field validation, a small percentage of slides (almost 3%) in this program were deemed unacceptable by participants. These results support the use of participant evaluation of cases to continually improve the quality of cases in this program. C1 Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. Baptist Mem Hosp, Dept Pathol, Miami, FL USA. Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. Coll Amer Pathologists, Northfield, IL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Colgan, TJ (reprint author), Mt Sinai Hosp, Dept Pathol & Lab Med, Suite 600,600 Univ Ave, Toronto, ON M5G 1X5, Canada. EM tcolgan@mtsinai.on.ca RI Colgan, Terence/J-2339-2016 NR 10 TC 3 Z9 3 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2005 VL 129 IS 9 BP 1093 EP 1096 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 959KY UT WOS:000231517800003 PM 16119978 ER PT J AU Deshpande, V Mino-Kenudson, M Brugge, W Lauwers, GY AF Deshpande, V Mino-Kenudson, M Brugge, W Lauwers, GY TI Autoimmune pancreatitis - More than just a pancreatic disease? A contemporary review of its pathology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; INFLAMMATORY MYOFIBROBLASTIC TUMOR; IDIOPATHIC CHRONIC-PANCREATITIS; BILIARY-TRACT DISEASE; STEROID-THERAPY; CHRONIC CHOLECYSTITIS; SJOGRENS-SYNDROME; IMAGING FEATURES; BILE-DUCT; PSEUDOTUMOR AB Context.-Autoimmune pancreatitis (AIP) is a chronic inflammatory condition of the pancreas constituting one quarter of Whipple resections performed for benign conditions in North America. Objective.-We review the clinical, radiologic, and characteristic histopathologic patterns of this disease and discuss the extrapancreatic manifestations of AIR Design.-We searched the literature using MEDLINE and OVID, related conference abstracts, and bibliographies of selected studies. Results.-Autoimmune pancreatitis predominantly affects elderly individuals, frequently presenting as obstructive jaundice and occasionally in association with other autoimmune diseases. The histology is characterized by a collar of periductal inflammation, obliterative phlebitis, and the absence of stigmata of alcoholic pancreatitis. A prepancreatectomy diagnosis can be rendered using a combination of clinical findings, radiologic features, elevated immunoglobulin G4 levels, endoscopic ultrasoundguided fine-needle aspiration biopsy, and response to steroids. The disease can involve the bile ducts (sclerosing cholangitis), gallbladder (lymphoplasmacytic sclerosing cholecystitis), and kidney (interstitial nephritis) and can form inflammatory masses in the lungs. Conclusions.-Despite significant evolution in our understanding of AIP, a prepancreatectomy diagnosis remains a challenge in the North American and European population. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 57 TC 81 Z9 90 U1 0 U2 3 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2005 VL 129 IS 9 BP 1148 EP 1154 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 959KY UT WOS:000231517800014 PM 16119989 ER PT J AU Goetz, LL Stiens, SA AF Goetz, LL Stiens, SA TI Abdominal electric stimulation facilitates penile vibratory stimulation for ejaculation after spinal cord injury: A single-subject trial SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Academy-of-Physical-Medicine-and-Rehabilitation CY NOV 20-24, 2002 CL ORLANDO, FL SP Amer Acad Phys Med & Rehabil DE ejaculation; electric stimulation; fertility; rehabilitation; spinal cord injuries ID RETROGRADE EJACULATION; SEMEN QUALITY; MEN; ELECTROEJACULATION; SPERM; PREDICTORS; EMISSION AB Objective: To compare the success rate of penile vibratory stimulation (PVS) alone with PVS and abdominal electric stimulation (AES). Design: Single-subject trials. Setting: Outpatient. Participant: Man with chronic T3 complete (American Spinal Injury Association Impairment Scale grade A) spinal cord injury. Spasticity, Babinski response, anal wink, and bulbocav-ernosus reflexes were all present. Intervention: Stimulation was presented to the frenulum using a Ferti Care Personal vibrator set at maximal settings (frequency, 110Hz; amplitude, 3.55mm). AES was applied to the abdomen using a commercially available muscle stimulator at maximal stimulus intensity and duration settings. Trials were randomized to PVS only or PVS plus AES. Main Outcome Measures: Presence or absence of ejaculation, and time to ejaculation. Results: Only 4 of 30 trials were positive with PVS alone, while 31 of 34 trials were positive with PVS plus AES. Additionally, 17 of 26 PVS trials, which were initially negative with PVS alone, were then positive with the addition of AES. This represents a clinically relevant improvement with use of AES. Time to ejaculation for positive trials with either technique was not statistically significant. Conclusions: AES significantly lowered the threshold for ejaculation elicited with vibratory stimulation and increased the success rate over that when PVS alone was used. C1 VA SCI Ctr 128, Spinal Cord Injury Ctr, Dallas, TX 75216 USA. Univ Texas, SW Med Ctr, Dept Phys Med & Rehabil, Dallas, TX 75230 USA. Vet Affairs Puget Sound Hlth Care Syst, Spinal Cord Injury Ctr, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Goetz, LL (reprint author), VA SCI Ctr 128, Spinal Cord Injury Ctr, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM lance.goetz@med.va.gov NR 24 TC 4 Z9 4 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2005 VL 86 IS 9 BP 1879 EP 1883 DI 10.1016/j.apmr.2005.03.023 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 962QM UT WOS:000231747300027 PM 16181958 ER PT J AU Binstadt, BA Nguyen, LT Huang, HC Bronson, R Benoist, C Mathis, D AF Binstadt, BA Nguyen, LT Huang, HC Bronson, R Benoist, C Mathis, D TI Spontaneous cardiac valve inflammation in the K/BxN murine arthritis model. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Binstadt, Bryce/N-1305-2013 OI Binstadt, Bryce/0000-0003-3127-3856 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S359 EP S360 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801438 ER PT J AU Choi, H Curhan, G AF Choi, H Curhan, G TI Dairy consumption and risk of incident gout in women - The nurses health SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S101 EP S102 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800204 ER PT J AU Choi, H Curhan, G AF Choi, H Curhan, G TI Adiposity, hypertension, diuretic use and risk of incident gout in women - The nurses health study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S733 EP S733 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803522 ER PT J AU Chou, RC Kim, ND Lee, DM Tager, AM Luster, AD AF Chou, RC Kim, ND Lee, DM Tager, AM Luster, AD TI Critical role for the leukotriene B4 receptor BLT1 in the K/BxN serum transfer model of rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S48 EP S49 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800047 ER PT J AU Gillett, CD Graham, RR Rodine, PR Ortmann, WA Williams, A Langefeld, CD Gaffney, PM Moser, KL Behrens, TW AF Gillett, CD Graham, RR Rodine, PR Ortmann, WA Williams, A Langefeld, CD Gaffney, PM Moser, KL Behrens, TW TI Characterization of systemic lupus erythematosus (SLE) locus susceptibility on chromosome 16q12 by linkage disequilibrium mapping. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Minnesota, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S275 EP S275 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801203 ER PT J AU Graham, RR de Bakker, P Burtt, N Ortmann, W Rodine, P Henderson, B Altshuler, D Behrens, T AF Graham, RR de Bakker, P Burtt, N Ortmann, W Rodine, P Henderson, B Altshuler, D Behrens, T TI Assessment of common variation in 32 sex steroid pathway genes for a contribution to SLE susceptibility. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Minneapolis, MN USA. Univ So Calif, Los Angeles, CA USA. RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S240 EP S240 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801102 ER PT J AU Kane, M Fishbein, R Phillips, K Savidge, E Seitz, A Peterson, J Kline-Schoder, R AF Kane, M Fishbein, R Phillips, K Savidge, E Seitz, A Peterson, J Kline-Schoder, R TI Comparison of goniometric and electronically instrumented range of motion measurements in subjects with restricted glenohumoral motion. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Creare Res & Dev Inc, Hanover, NH 03755 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S525 EP S525 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802417 ER PT J AU Kay, J Matteson, EL Dasgupta, B Nash, P Durez, P Hall, S Han, J Rahman, MU AF Kay, J Matteson, EL Dasgupta, B Nash, P Durez, P Hall, S Han, J Rahman, MU TI Subcutaneous injection of CNTO 148 compared with placebo in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double-blind, dose-ranging trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin Med, Rochester, MN USA. Ave Specialist Ctr, Cotton Tree, Australia. Clin Univ St Luc, Serv Rhumatol, B-1200 Brussels, Belgium. Cabrini Med Ctr, New York, NY USA. Centocor Inc, Malvern, PA 19355 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S711 EP S711 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803466 ER PT J AU Naqibuddin, M Sampedro, M Wallace, DJ Weisman, MH Brey, RL Holliday, SL Carson, KA Petri, M AF Naqibuddin, M Sampedro, M Wallace, DJ Weisman, MH Brey, RL Holliday, SL Carson, KA Petri, M TI Anti-NR2 and anti-dsDNA in newly diagnosed systemic lupus erythematosus: Analysis of cognitive function, brain MRI and PET. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S621 EP S622 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803216 ER PT J AU Naqibuddin, M Wallace, DJ Weisman, MH Brey, RL Sampedro, M Carson, KA Holliday, SL Petri, M AF Naqibuddin, M Wallace, DJ Weisman, MH Brey, RL Sampedro, M Carson, KA Holliday, SL Petri, M TI Change in cognitive function in newly diagnosed systemic lupus erythematosus patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S380 EP S380 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802004 ER PT J AU Naqibuddin, M Wallace, DJ Weisman, MH Brey, RL Sampedro, M Carson, KA Holliday, SL Petri, M AF Naqibuddin, M Wallace, DJ Weisman, MH Brey, RL Sampedro, M Carson, KA Holliday, SL Petri, M TI Depression is associated with poorer cognitive function in newly diagnosed systemic lupus erythematosus patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S379 EP S380 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802003 ER PT J AU Nigrovic, PA Monach, PA Gurish, MF Mathis, D Benoist, C Iwakura, Y Lee, DM AF Nigrovic, PA Monach, PA Gurish, MF Mathis, D Benoist, C Iwakura, Y Lee, DM TI Mast cells initiate K/BxN serum transfer arthritis via IL-1. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Ctr Med Expt, Tokyo, Japan. RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S362 EP S362 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801446 ER PT J AU Polinski, JM Katz, JN Finkelstein, J Canning, C Avorn, J Arnold, M Licari, A Solomon, DH AF Polinski, JM Katz, JN Finkelstein, J Canning, C Avorn, J Arnold, M Licari, A Solomon, DH TI Osteoporosis prevention behaviors: Relationship with patient factors. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S440 EP S440 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207802177 ER PT J AU Tagoe, CE Marjanovic, N Jacobson, DR Pillinger, MH AF Tagoe, CE Marjanovic, N Jacobson, DR Pillinger, MH TI Annexin-1 peptide Ac2-26 stimulates matrix metalloproteinase secretion in rheumatoid arthritis synovial fibroblasts. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10467 USA. NYU, Sch Med, New York, NY USA. Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S45 EP S46 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800038 ER PT J AU Todd, DJ Kay, J AF Todd, DJ Kay, J TI Nephrogenic fibrosing dermopathy is prevalent among patients receiving hemodialysis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S592 EP S593 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207803129 ER PT J AU Budoff, JE Rodin, D Ochiai, D Nirschl, RP AF Budoff, JE Rodin, D Ochiai, D Nirschl, RP TI Arthroscopic rotator cuff debridement without decompression for the treatment of tendinosis SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE rotator cuff; debridement; partial-thickness tears; impingement syndrome ID FULL-THICKNESS TEARS; NONOPERATIVE MANAGEMENT; FOLLOW-UP; ASYMPTOMATIC SHOULDERS; IMPINGEMENT SYNDROME; ACROMIOPLASTY; REPAIR; DEGENERATION; TENDON; ARCH AB Purpose: The treatment of rotator cuff injury in the absence of a full-thickness tear has traditionally consisted of acromioplasty. However, this disorder may also be treated by arthroscopic rotator cuff debridement without acromioplasty. Our previous study of 79 shoulders so treated reported 87% good or excellent results at an average 53-month follow-up. The purpose of this article is to report the long-term, average 9.5-year follow-up of this cohort. Type of Study: Long-term follow-up of case series. Methods: We retrospectively reviewed the records of 62 shoulders in 60 patients who had undergone arthroscopic rotator cuff debridement for partial-thickness rotator cuff tears. Demographic criteria, residual pain, and the ability to return to recreational athletics were noted. The UCLA Shoulder Score and the Simple Shoulder Test scores were determined and statistical analysis performed. Results: Using the UCLA Shoulder Score, there were 79% excellent or good results at an average 114 months of follow-up. Patients with Workers' Compensation claims had significantly worse results, with only 40% rated good or excellent. Of the 60 patients, 77% had no or only minimal pain, 57% were still able to perform recreational athletics without difficulty, and 20% could participate at a lower level of intensity. Conclusions: Arthroscopic debridement of rotator cuff injury in the absence of a full-thickness tear has good long-term results and minimizes additional surgical trauma. Level of Evidence: Level IV, case series. C1 Baylor Coll Med, Houston Vet Adm Med Ctr, Dept Orthopaed Surg, Houston, TX 77030 USA. Virginia Hosp Ctr, Nirschl Orthopaed Ctr Sportsmed & Joint Reconstru, Dept Orthopaed Surg, Arlington, VA USA. RP Budoff, JE (reprint author), 6550 Fannin #2525, Houston, TX 77030 USA. EM Jbudoff@houston.rr.com NR 52 TC 32 Z9 34 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD SEP PY 2005 VL 21 IS 9 BP 1081 EP 1089 DI 10.1016/j.arthro.2005.05.019 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 969YX UT WOS:000232273300020 PM 16171633 ER PT J AU Park, TS Kim, YS AF Park, TS Kim, YS TI Neuropraxia of the cutaneous nerve of the cervical plexus after shoulder arthroscopy (vol 21, pg 631, 2005) SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Correction C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Park, TS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD SEP PY 2005 VL 21 IS 9 BP CP5 EP CP5 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 969YX UT WOS:000232273300012 ER PT J AU Cohen, LJ Fitzgerald, SG Lane, S Boninger, ML AF Cohen, LJ Fitzgerald, SG Lane, S Boninger, ML TI Development of the seating and mobility script concordance test for spinal cord injury: Obtaining content validity evidence SO ASSISTIVE TECHNOLOGY LA English DT Article DE professional practice; clinical competence; rehabilitation; seating and mobility; educational measurement; validity evidence ID DIAGNOSTIC KNOWLEDGE; PERFORMANCE; EXPERTISE; CAPACITY AB The appropriateness of a consumer's seating and mobility system varies considerably depending on the competence, proficiency, and experience of the professionals assisting the user. At present, there is a scarcity of skilled and knowledgeable therapists to evaluate and recommend seating and mobility devices. There is also a lack of measurement tests available to evaluate the impact of educational experiences or clinical practice on the ability to make specialized clinical decisions about seating and mobility needs. The Seating and Mobility Script Concordance Test (SMSCT) is a new assessment tool, grounded in the hypothetico-deductive and schema theories of clinical reasoning. The test is designed to assess therapists by examining the organization of their knowledge, associations between items of their knowledge, and the adequacy of their clinical decisions as compared to expert consensus. This article describes the interview, test development, and content/item review processes used for the collection of content validity evidence. The iterative process employed and the appraisal of the content validity evidence that resulted in the final version of the SMSCT are presented. The SMSCT appears to be a promising assessment tool representing content within the domain of seating and mobility for individuals with spinal cord injuries. The process utilized to develop the SMSCT in spinal cord injury can be replicated for other diagnoses and domains. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Educ, Dept Educ Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Engn, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, 151R-1,7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 25 TC 7 Z9 7 U1 0 U2 3 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD FAL PY 2005 VL 17 IS 2 BP 122 EP 132 PG 11 WC Rehabilitation SC Rehabilitation GA 004BM UT WOS:000234727000004 PM 16392716 ER PT J AU Cooper, RA Ding, D Simpson, R Fitzgerald, SG Spaeth, DM Guo, SF Koontz, AM Cooper, R Kim, J Boninger, ML AF Cooper, RA Ding, D Simpson, R Fitzgerald, SG Spaeth, DM Guo, SF Koontz, AM Cooper, R Kim, J Boninger, ML TI Virtual reality and computer enhanced training applied to wheeled mobility: An overview of work in Pittsburgh SO ASSISTIVE TECHNOLOGY LA English DT Review DE virtual reality; assistive technology; simulation; wheelchairs ID POWER-ASSISTED WHEELCHAIR; PUSHRIM BIOMECHANICS; EXERCISE; PROPULSION; SYSTEM; REHABILITATION; ADHERENCE; ERGOMETRY; POSITION; KINETICS AB Some aspects of assistive technology can be enhanced by the application of virtual reality. Although virtual simulation offers a range of new possibilities, learning to navigate in a virtual environment is not equivalent to learning to navigate in the real world. Therefore, virtual reality simulation is advocate as a useful preparation for assessment and training within the physical environment. We are engaged in several efforts to develop virtual environments and devices for mobility skills assessment and training, exercise training, and environment assessment. Virtual reality offers wheelchair users a training tool in different risk-free environments without any indoor (e.g., walls, furniture, and stairs) and outdoor (e.g., curb cuts, uneven terrain, and street traffic) physical constraints. Virtual reality technology will probably become more common in the field of assistive technology, especially given the rapid expansion of gaming technology and the continued exponential growth of computing power. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil R&D Ctr Excellence Wheelchairs & Assoc, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil R&D Ctr Excellence Wheelchairs & Assoc, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 46 TC 13 Z9 13 U1 3 U2 6 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD FAL PY 2005 VL 17 IS 2 BP 159 EP 170 PG 12 WC Rehabilitation SC Rehabilitation GA 004BM UT WOS:000234727000007 PM 16392719 ER PT J AU Sookman, D Abramowitz, JS Calamari, JE Wilhelm, S McKay, D AF Sookman, D Abramowitz, JS Calamari, JE Wilhelm, S McKay, D TI Subtypes of obsessive-compulsive disorder: Implications for specialized cognitive behavior therapy SO BEHAVIOR THERAPY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; FACTOR-ANALYZED SYMPTOM; CONTROLLED-TRIAL; DIMENSIONS; EXPOSURE; PREDICTORS; INVENTORY; THOUGHTS; SCALE AB Although obsessive-compulsive disorder (OCD) is a heterogeneous condition, OCD subtypes have received limited attention in trials of cognitive behavior therapy (CBT). Because many patients with OCD do not respond optimally to CBT, it is important for clinicians to consider whether variability in treatment response is related to symptom presentation. Treatment modifications for patients without overt compulsions or with hoarding symptoms show promise. In this article we discuss the available research addressing the treatment of OCD subtypes, review the clinical characteristics and treatment recommendations for prominent OCD subtypes, raise the prospect of using dysfunctional beliefs as a potentially helpful conceptual approach to subtyping OCD and matching treatment to subtypes, and consider future directions in the treatment of OCD subtypes. C1 McGill Univ, Ctr Hlth, Obsess Compuls Disorder Clin, Dept Psychol, Montreal, PQ H3A 1A1, Canada. Mayo Clin, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Fordham Univ, Bronx, NY 10458 USA. RP Sookman, D (reprint author), McGill Univ, Ctr Hlth, Obsess Compuls Disorder Clin, Dept Psychol, 1025 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM debbie.sookman@mcgill.ca NR 64 TC 38 Z9 38 U1 3 U2 12 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD FAL PY 2005 VL 36 IS 4 BP 393 EP 400 DI 10.1016/S0005-7894(05)80121-2 PG 8 WC Psychology, Clinical SC Psychology GA 003QB UT WOS:000234695600010 ER PT J AU Desai, J Demetri, GD AF Desai, J Demetri, GD TI Recombinant human erythropoietin in cancer-related anemia: an evidence-based review SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; RECEIVING NONPLATINUM CHEMOTHERAPY; STAGE RENAL-DISEASE; EPOETIN-ALPHA; DOUBLE-BLIND; FUNCTIONAL ASSESSMENT; COMMUNITY ONCOLOGY; OPEN-LABEL; THERAPY AB Anemia is a common complication of cancer or anticancer therapy, with a significant negative impact on the functional status of patients and their quality of life (QCL). Recombinant human erythropoietin (EPO) was developed in the 1980's and was initially developed for the treatment of anemia associated with chronic renal failure. Subsequently, randomized, placebo-controlled clinical trials in the oncology setting were performed in the early 1990's. These studies demonstrated in cancer patients that EPO could increase the levels of hemoglobin (Hb), decrease the need for red blood cell transfusions, and also suggested that these outcomes were associated with improved QOL metrics as reported by the patients themselves. Based on the results of these studies, EPO was granted regulatory approval to be used for the treatment of anemia in patients with non-myeloid malignancies where anemia was due to the effect of concomitantly administered chemotherapy. To further expand the findings of the registration studies, and to develop more complete QOL data, three similarly designed open-label community-based studies were performed, enrolling a total of approximately 7000 patients. These studies consistently demonstrated in the supportive care of cancer patients receiving chemotherapy that the use of EPO could induce increases in the levels of Hb and that these correlated with patient-reported improvements in QOL metrics. The correlation between an improvement in Hb and QOL has also been confirmed in a larger randomized, placebo-controlled trial. Careful analyses of data from this study also helped support earlier findings that EPO could be effective for patients with varying degrees of anemia, and that increasing and maintaining Hb levels close to the physiologically normal levels resulted in the optimal improvements in QOL. While further investigations of EPO as a mechanism to improve the antineoplastic efficacy of chemoradiotherapy have not yet been positive, the overall experience with this agent remains very favorable after extensive studies and long-term clinical use in oncology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Shields Warren Bldg Room 530,44 Binney St, Boston, MA 02115 USA. EM gdemetri@partners.org NR 34 TC 13 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD SEP PY 2005 VL 18 IS 3 BP 389 EP 406 DI 10.1016/j.beha.2005.01.018 PG 18 WC Hematology SC Hematology GA 919JT UT WOS:000228615000002 PM 15792913 ER PT J AU Reynolds, F Weissleder, R Josephson, L AF Reynolds, F Weissleder, R Josephson, L TI Protamine as an efficient membrane-translocating peptide SO BIOCONJUGATE CHEMISTRY LA English DT Article ID ARGININE-RICH PEPTIDES; HIV-1 TAT PROTEIN; CELL-PENETRATING PEPTIDES; INTRACELLULAR DELIVERY; TRANSDUCTION DOMAINS; NANOPARTICLES; SURFACE; DNA; INTERNALIZATION; CONJUGATION AB Protamine, a mixture of positively charged proteins from salmon roe used in diverse pharmaceutical applications, was reacted with the N-hydroxysuccinimide ester of tetramethylrhodamine to yield tetramethylrhodamine-labeled protamines (Pro(Rh)) containing one mole of fluorochrome per mole of protein. The internalization of tetramethylrhodamine-labeled protamine (Pro(Rh)) and the fluorescein-labeled tat peptide (Tat(Fl)) showed a similar dependence on time and concentration. Pro(Rh) and Tat(Fl) showed strong nuclear localizations, evident with both live cells and fixed cells costained with DAPI, a nuclear stain. The loss of fluorescence when cells were loaded with Pro(Rh) or Tat(Fl) was similar, further supporting a strong similarity between these two materials. Finally, when Pro(Ph) was covalently attached to the amino-CLIO nanoparticle, the cellular uptake of the nanoparticle was greatly enhanced. All experiments were performed with HeLa and CaCo-2 cells with similar results. These observations imply that protamine, a protein in regular clinical use, might be used for the design of novel membrane translocating/nuclear localizing pharmaceuticals whose development was initiated with other membrane-translocating peptides. In addition, the fluorescent protamines developed here might be used to further our understanding of this important pharmaceutical. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. EM ljosephson@partners.org FU NIBIB NIH HHS [R01-EB00662, R01 EB004626] NR 31 TC 62 Z9 65 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2005 VL 16 IS 5 BP 1240 EP 1245 DI 10.1021/bc0501451 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 967CX UT WOS:000232070200027 PM 16173804 ER PT J AU Hilderbrand, SA Kelly, KA Weissleder, R Tung, CH AF Hilderbrand, SA Kelly, KA Weissleder, R Tung, CH TI Monofunctional near-infrared fluorochromes for imaging applications SO BIOCONJUGATE CHEMISTRY LA English DT Article ID HEPTAMETHINE CYANINE DYES; SUCCINIMIDYL ESTERS; FLUORESCENT-PROBES; LABELING REAGENTS; INDOCYANINE GREEN; PHAGE DISPLAY; CELL AB In this report, the development of a new class of monocarboxylate functionalized cyanine derivatives using improved synthetic procedures is detailed. The employed synthetic strategy relies on efficient nucleophilic attack of alkyl-thiols on cyanine dyes bearing chloro-substituted polymethinic linkers. Monocarboxylate derivatized fluorochromes (CyTE dyes) can be prepared in one step in greater than 90% yield without the need for additional purification. Several of the fluorochromes synthesized by this route show no tendency to aggregate in aqueous solution and have excitation and emission maxima greater than 800 nm. The potential utility of the CyTE fluorochromes was demonstrated through direct labeling of phage displaying a vascular cellular adhesion molecule-1 (VCAM-1) targeting peptide. Endothelial cell internalization of the VCAM-1 targeted phage was monitored via near-infrared fluorescence microscopy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Room 5406,149 13th St, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01-CA99385, R21-CA114149, T32-CA79443] NR 32 TC 83 Z9 87 U1 2 U2 29 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2005 VL 16 IS 5 BP 1275 EP 1281 DI 10.1021/bc0501799 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 967CX UT WOS:000232070200031 PM 16173808 ER PT J AU Scholtens, D Vidal, M Gentleman, R AF Scholtens, D Vidal, M Gentleman, R TI Local modeling of global interactome networks SO BIOINFORMATICS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; YEAST SACCHAROMYCES-CEREVISIAE; SCALE DATA; COMPLEXES; IDENTIFICATION; ANNOTATION; SUBUNITS; EIF5; CELL; RNA AB Motivation: Systems biology requires accurate models of protein complexes, including physical interactions that assemble and regulate these molecular machines. Yeast two-hybrid (Y2H) and affinity-purification/mass-spectrometry (AP-MS) technologies measure different protein-protein relationships, and issues of completeness, sensitivity and specificity fuel debate over which is best for high-throughput 'interactome' data collection. Static graphs currently used to model Y2H and AP-MS data neglect dynamic and spatial aspects of macromolecular complexes and pleiotropic protein function. Results: We apply the local modeling methodology proposed by Scholtens and Gentleman (2004) to two publicly available datasets and demonstrate its uses, interpretation and limitations. Specifically, we use this technology to address four major issues pertaining to protein-protein networks. (1) We motivate the need to move from static global interactome graphs to local protein complex models. (2) We formally show that accurate local interactome models require both Y2H and AP-MS data, even in idealized situations. (3) We briefly discuss experimental design issues and how bait selection affects interpretability of results. (4) We point to the implications of local modeling for systems biology including functional annotation, new complex prediction, pathway interactivity and coordination with gene-expression data. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Computat Biol, Seattle, WA 98109 USA. RP Scholtens, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM dscholtens@northwestern.edu NR 30 TC 55 Z9 55 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP 1 PY 2005 VL 21 IS 17 BP 3548 EP 3557 DI 10.1093/bioinformatics/bti567 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 958UA UT WOS:000231472500014 PM 15998662 ER PT J AU Rush, AJ Marangell, LB Sackeim, HA George, MS Brannan, SK Davis, SM Howland, R Kling, MA Rittberg, BR Burke, WJ Rapaport, MH Zajecka, J Nierenberg, AA Husain, MM Ginsberg, D Cooke, RG AF Rush, AJ Marangell, LB Sackeim, HA George, MS Brannan, SK Davis, SM Howland, R Kling, MA Rittberg, BR Burke, WJ Rapaport, MH Zajecka, J Nierenberg, AA Husain, MM Ginsberg, D Cooke, RG TI Vagus nerve stimulation for treatment-resistant depression: A randomized, controlled acute phase trial SO BIOLOGICAL PSYCHIATRY LA English DT Article DE vagus nerve stimulation (VNS); major depressive disorder; bipolar disorder; treatment-resistant depression (TRD); clinical trial; efficacy; side effects ID STRUCTURED INTERVIEW GUIDE; RATING-SCALE; ELECTROCONVULSIVE-THERAPY; MEDICATION RESISTANCE; CLINICAL-RESPONSE; PARTIAL SEIZURES; LONG-TERM; EPILEPSY; VNS; SYMPTOMATOLOGY AB Background: Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy. Methods: This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with noupsychotic major depressive disorder (n = 210) or nonpsycbotic, depressed phase, bipolar disorder (n = 25). in the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sbam VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (>= 50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD24]). Results: At 10-weeks, HRSD24 response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110)groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology Self-Report (IDS-SR30), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events. Conclusions: This study did not yield definitive evidence of short-term efficacy\for adjunctive VNS in treatment-resistant depression. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Baylor Coll Med, S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. Cyberon Inc, Houston, TX USA. New York State Psychiat Inst & Hosp, Dept Biol Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. NYU, Med Ctr, Dept Psychiat, New York, NY 10016 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. Quintiles Inc, Res Triangle Pk, NC USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Maryland, Sch Med, Dept Vet Affairs, Mental Hlth Serv Line, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. Univ Nebraska, Med Ctr, Dept Psychiat, Omaha, NE 68182 USA. Univ Calif San Diego, Med Ctr, Dept Psychiat, La Jolla, CA 92093 USA. Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM John.Rush@UTSouthwestern.edu RI Kling, Mitchel/F-4152-2010; Howland, Robert/K-6937-2015; OI Kling, Mitchel/0000-0002-2232-1409; Howland, Robert/0000-0002-6533-6010; Rush, Augustus/0000-0003-2004-2382 NR 39 TC 239 Z9 247 U1 6 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 SEP 1 PY 2005 VL 58 IS 5 BP 347 EP 354 DI 10.1016/j.biopsych.2005.05.025 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 959YD UT WOS:000231554600001 PM 16139580 ER PT J AU George, MS Rush, AJ Marangell, LB Sackeim, HA Brannan, SK Davis, SM Howland, R Kling, MA Moreno, F Rittberg, B Dunner, D Schwartz, T Carpenter, L Burke, M Ninan, P Goodnick, P AF George, MS Rush, AJ Marangell, LB Sackeim, HA Brannan, SK Davis, SM Howland, R Kling, MA Moreno, F Rittberg, B Dunner, D Schwartz, T Carpenter, L Burke, M Ninan, P Goodnick, P TI A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE vagus nerve stimulation; major depressive disorder; bipolar disorder; treatment-resistant depression; clinical trial; efficacy; side effects ID REPORT QIDS-SR; ELECTROCONVULSIVE-THERAPY; MAJOR DEPRESSION; CONTINUATION PHARMACOTHERAPY; PSYCHOMETRIC EVALUATION; MEDICATION RESISTANCE; CLINICAL-RESPONSE; QUICK INVENTORY; SYMPTOMATOLOGY; OUTCOMES AB Background: Previous reports have described the effects of vagus nerve stimulation plus treatment as usual (VNS + TAU) during open trials of patients with treatment-resistant depression (TRD). To better understand these effects on long-term outcome, we compared 12-month VNS + TAU outcomes with those of a comparable TPD group. Metbods: Admission criteria were similar for those receiving VNS + TAU (n = 205) or only TAU (n = 124). In the primary analysis, repeated-measures linear regression was used to compare the VNS + TAU group (monthly data) with the TAU group (quarterly data) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR30). Results: The two groups bad similar baseline demographic data, psychiatric and treatment histories, and degrees of treatment resistance, except that more TAU participants bad at least 10 prior major depressive episodes, and the VNS + TAU group bad more electroconvulsive therapy before study entry. Vagus nerve stimulation plus treatment as usual was associated with greater improvement per month in IDS-SR30 than TAU across 12 months (p < . 001). Response rates according to the 24-item Hamilton Rating Scale for Depression (last observation carried forward) at 12 months were 27% for VNS + TAU and 13% for TAU (p < .011). Both groups received similar TAU (drugs and electroconvulsive therapy) during follow-up. Conclusions: This comparison of two similar but nonrandomized TRD groups showed that VNS + TAU was associated with a greater antidepressant benefit over 12 months. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Baylor Coll Med, S Cent Mental Illness Res, Educ & Clin Ctr, Dept Psychiat, Houston, TX 77030 USA. Cyberon Inc, Houston, TX USA. New York State Psychiat Inst & Hosp, Dept Biol Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. SUNY Syracuse, Dept Psychiat, Syracuse, NY 13210 USA. Quintiles Inc, Durham, NC USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Mental Hlth Clin Ctr, Dept Vet Affairs, Baltimore, MD USA. Univ Arizona, Dept Psychiat, Tucson, AZ USA. Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. Univ Washington, Ctr Anxiety & Depress, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Butler Hosp, Dept Psychiat, Providence, RI 02906 USA. Inst Psychiat Res Via Christi, Wichita, KS USA. Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA. Univ Miami, Dept Psychiat, Miami, FL 33152 USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St,502-N,POB 250861, Charleston, SC 29425 USA. EM georgem@musc.edu RI Kling, Mitchel/F-4152-2010; Howland, Robert/K-6937-2015; OI Kling, Mitchel/0000-0002-2232-1409; Howland, Robert/0000-0002-6533-6010; Rush, Augustus/0000-0003-2004-2382; Ninan, Philip/0000-0001-6633-1142 NR 25 TC 179 Z9 185 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2005 VL 58 IS 5 BP 364 EP 373 DI 10.1016/j.biopsych.2005.07.028 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 959YD UT WOS:000231554600003 PM 16139582 ER PT J AU Holt, DJ Bachus, SE Hyde, TM Wittie, M Herman, MM Vangel, M Saper, CB Kleinman, JE AF Holt, DJ Bachus, SE Hyde, TM Wittie, M Herman, MM Vangel, M Saper, CB Kleinman, JE TI Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia: An in situ hybridization study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE basal ganglia; cholinergic; in situ hybridization; postmortem; schizophrenia; striatum ID GLUTAMIC-ACID DECARBOXYLASE; MESSENGER-RNA LEVELS; ANTIPSYCHOTIC-DRUGS; ALZHEIMERS-DISEASE; GENE-EXPRESSION; ANTICHOLINERGIC MEDICATION; INSITU HYBRIDIZATION; TYROSINE-HYDROXYLASE; NICOTINIC RECEPTORS; CAUDATE-PUTAMEN AB Background: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. Methods: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and beta-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and beta-actin mRNA expression levels were measured. Results: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of beta-actin mRNA expression throughout the striation, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. Conclusions: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia. C1 Massachusetts Gen Hosp E, Dept Psychiat, Charlestown, MA 02129 USA. NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Brookline, MA USA. RP Holt, DJ (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, 149 13th St,Room 2625, Charlestown, MA 02129 USA. EM dholt@partners.org NR 63 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2005 VL 58 IS 5 BP 408 EP 416 DI 10.1016/j.biopsych.2005.04.007 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 959YD UT WOS:000231554600008 PM 16023618 ER PT J AU Treister, NS Woo, SB O'Holleran, EW Lehmann, LE Parsons, SK Guinan, EC AF Treister, NS Woo, SB O'Holleran, EW Lehmann, LE Parsons, SK Guinan, EC TI Oral chronic graft-versus-host disease in pediatric patients after hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE graft-versus-host disease; hematopoietic stem cell transplantation; pediatric patients; oral lesions ID BONE-MARROW-TRANSPLANTATION; SUPERFICIAL MUCOCELES; CHILDREN; MANIFESTATIONS; DIAGNOSIS; CANCERS; IMPACT AB Chronic graft-versus-host disease (cGVHD) is a serious and potentially life-threatening complication of hematopoietic stem cell transplantation. This study, which is the largest single-center series of oral disease in pediatric patients with cGVHD, describes the oral findings in 49 consecutive patients seen in a pediatric multidisciplinary cGVHD clinic. All consecutive patients seen at the multidisciplinary pediatric hematopoietic stem cell transplantation/cGVHD clinic at the Dana-Farber Cancer Institute (Boston, MA) from July 2001 through October 2003 were included in this study. Subjective and objective assessments of mucosal, salivary gland, and sclerotic pathology were performed for each patient, and specific therapy was initiated when indicated. Oral mucosal cGVHD was identified in 22 (45%) of 49 patients. Only 4 (8%) of 49 patients reported mouth pain, and all patients reported being able to eat well. All patients who required specific therapy for their oral mucosal cGVHD (45%) were already taking at least 1 immunomodulatory agent; however, efficacy of treatment was difficult to assess because of inconsistent follow-up periods. Subjective and objective salivary gland and sclerotic disease were observed far less often. Oral mucosal pathology is common in these patients, and appropriate diagnosis and management of oral lesions is critical to reduce patient morbidity and to improve quality of life. The apparent lack of salivary gland involvement was notable. Developing validated age-appropriate evaluation strategies and identifying effective treatment guidelines will be invaluable in the future management of these patients. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Harvard Univ, Sch Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Med & Pediat, Boston, MA 02111 USA. RP Treister, NS (reprint author), Brigham & Womens Hosp, Div Oral Med, Ctr Oral Dis, 75 Francis St, Boston, MA 02115 USA. EM ntreister@partners.org FU NIDCR NIH HHS [K16 DE00275] NR 29 TC 34 Z9 37 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 SEP PY 2005 VL 11 IS 9 BP 721 EP 731 DI 10.1016/j.bbmt.2005.06.002 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 965GQ UT WOS:000231939000009 PM 16125643 ER PT J AU Yurkovetskiy, A Choi, SW Hiller, A Yin, M McCusker, C Syed, S Fischman, AJ Papisov, MI AF Yurkovetskiy, A Choi, SW Hiller, A Yin, M McCusker, C Syed, S Fischman, AJ Papisov, MI TI Fully degradable hydrophilic polyals for protein modification SO BIOMACROMOLECULES LA English DT Article ID COMMUNICATION; STORAGE; TRYPSIN AB Modification of proteins with hydrophilic polymers is an effective strategy for regulation of protein pharmacokinetics. However, conjugates of slowly or nonbiodegradable materials, such as poly(ethylene glycol), are known to cause long-lasting cell vacuolization, in particular in renal epithelium. Conjugates of more degradable polymers, e.g., polysaccharides, have a significant risk of immunotoxicity. Polymers that combine complete degradability, long circulation in vivo, and low immuno and chemical toxicity would be most beneficial as protein conjugate components. This study explores new fully biodegradable hydrophilic polymers, hydrophilic polyals. They are nontoxic, stable at physiological conditions, and undergo proton-catalyzed hydrolysis at lysosomal pH. The model enzyme-polyal conjugates were prepared with 61-98% yield using conventional and novel conjugation techniques and retained 90-95% of specific activity. The model conjugates showed a significant prolongation of protein circulation in rodents, with a 5-fold reduction in the renal accumulation. The data suggests that hydrophilic polyals may be useful in designing protein conjugates with improved properties. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Papisov, MI (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu RI McCusker, Catherine/G-2795-2010; OI McCusker, Catherine/0000-0001-9580-3612; Papisov, Mikhail/0000-0003-4716-2122 FU NCRR NIH HHS [R21-RR14221, R21 RR014221, R21 RR014221-01A1, R21 RR014221-02] NR 28 TC 8 Z9 9 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD SEP-OCT PY 2005 VL 6 IS 5 BP 2648 EP 2658 DI 10.1021/bm049210k PG 11 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 964RW UT WOS:000231899200034 PM 16153103 ER PT J AU Papisov, MI Hiller, A Yurkovetskiy, A Yin, M Barzana, M Hillier, S Fischman, AJ AF Papisov, MI Hiller, A Yurkovetskiy, A Yin, M Barzana, M Hillier, S Fischman, AJ TI Semisynthetic hydrophilic polyals SO BIOMACROMOLECULES LA English DT Article ID CONTAINING LIPOTEICHOIC ACID; STREPTOCOCCUS-SANGUIS; OXIDATION; PERIODATE; BACTERIA; DEXTRANS; DELIVERY AB Nonbioadhesive, fully biodegradable soluble polymers would be very instrumental in advanced biomedical applications, such as gene and drug delivery and tissue engineering. However, rational development of such materials is hindered by the complexity of macromolecule interactions with biological milieu. The prevalence of carbohydrates in naturally occurring interface structures suggests an alternative, biomimetic approach. Interface carbohydrates, regardless of their biological function, have common nonsignaling substructures (e.g., acetal and ketal groups, secondary and primary alcohols). We hypothesized that hydrophilic polymers (polyals) consisting of acyclic units built of nonsignaling carbohydrate substructures would be highly biocompatible and nonbioadhesive, while intrachain acetal or ketal groups would enable nonenzymatic biodegradation upon uptake by cells. Acyclic hydrophilic polyals can be prepared via either polymerization of suitable monomers or lateral cleavage of cyclic polyals (e.g., polysaccharides). In this study, model polyals were produced via lateral cleavage of polyaldoses and polyketoses. Best results were achieved using dextran B-512 as a precursor. The resultant poly[hydroxymethylethylene hydroxymethylformal], in agreement with the hypothesis, demonstrated excellent biological properties and technological flexibility. Materials of this type can potentially have several applications in pharmacology and bioengineering. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Papisov, MI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu OI Papisov, Mikhail/0000-0003-4716-2122 FU NCRR NIH HHS [R21 RR014221, R21 RR014221-01A1, R21 RR014221-02, R21-RR14221] NR 27 TC 10 Z9 10 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD SEP-OCT PY 2005 VL 6 IS 5 BP 2659 EP 2670 DI 10.1021/bm0502157 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 964RW UT WOS:000231899200035 PM 16153104 ER PT J AU Fischer, TH Thatte, HS Nichols, TC Bender-Neal, DE Bellinger, DA Vournakis, JN AF Fischer, TH Thatte, HS Nichols, TC Bender-Neal, DE Bellinger, DA Vournakis, JN TI Synergistic platelet integrin signaling and factor XII activation in poly-N-acetyl glucosamine fiber-mediated hemostasis SO BIOMATERIALS LA English DT Article DE poly-N-acetylglucosamine; hemostatis; platelet; integrin; Factor XII ID VON-WILLEBRAND-FACTOR; GLYCOPROTEIN IB-IX; CONTACT ACTIVATION; ENDOTHELIAL-CELLS; BLOOD PLATELETS; ADHESION; BINDING; SURFACE; GLASS; MECHANISMS AB The polymer poly-N-acetylglucosarnine (pGlcNAc) containing fiber material is becoming increasingly important as a topical agent for hemostasis at Wound sites. The pGlcNAc polymeric fiber provides hemostasis through redundant mechanisms that include platelet activation for fibrin network formation. The research presented here better defines the mechanism for the effect of pGlcNAc containing fibers on platelet-mediated processes. Adsorption experiments demonstrated that pGlcNAc fibers tightly bind most major plasma proteins and a specific sub-set Of platelet surface proteins, including the integrin beta(3) subunit (CD61) and the von Willebrand receptor GPlb (CD42b). The result of this interaction is a platelet-dependent acceleration of fibrin gel formation. Accelerated fibrin polymerization is sensitive to factor XII inhibition by corn trypsin inhibitor and integrin inactivation with intearilin. Confocal Microscopy Studies show that when platelet integrins contact plasma protein-saturated pGlcNAc fibers, an increase in intracellular free calcium for platelet activation Occurs to drive surface expression of phosphatidyl serine (PS). Thus, a catalytic surface for thrombin generation and accelerated fibrin clot formation results from the interaction of platelets with pGlcNAc. These findings, when considered with the observation that pGlcNAc fibers also induce red blood cell agglutination and vasoconstriction, provides an explanation for the ability of the pGlNAc material to provide hemostasis in a wide variety of clinical applications. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ N Carolina, Francis Owen Blood Res Lab, Dept Pathol & Lab Med, Chapel Hill, NC 27516 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,VA Boston Healthcare Syst, Boston, MA USA. Med Univ S Carolina, Sch Grad Studies, Charleston, SC 29425 USA. RP Fischer, TH (reprint author), Univ N Carolina, Francis Owen Blood Res Lab, Dept Pathol & Lab Med, 350 S Old Fayetteville Rd, Chapel Hill, NC 27516 USA. EM tfischer@med.unc.edu FU NHLBI NIH HHS [R24 HL063098] NR 52 TC 39 Z9 39 U1 1 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2005 VL 26 IS 27 BP 5433 EP 5443 DI 10.1016/j.biomaterials.2005.01.023 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 926YB UT WOS:000229158500002 PM 15860200 ER PT J AU Sundback, CA Shyu, JY Wang, YD Faquin, WC Langer, RS Vacanti, JP Hadlock, TA AF Sundback, CA Shyu, JY Wang, YD Faquin, WC Langer, RS Vacanti, JP Hadlock, TA TI Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material SO BIOMATERIALS LA English DT Article DE biocompatibility; Schwann cells; nerve guide; fibrosis degradation ID EPSILON-CAPROLACTONE POLYMER; PERIPHERAL-NERVE; SCHWANN-CELLS; TRIMETHYLENE CARBONATE; LONG GAPS; L-LACTIDE; REGENERATION; TUBE; CONDUITS; PROTEASE AB No satisfactory method currently exists for bridging neural defects. Autografts lead to linadequate functional recovery. and most available artificial neural conduits possess unfavorable swelling and pro-inflammatory characteristics. This Study examined the biocompatibility of a novel biodegradable elastomer, poly(glycerol sebacate) (PGS), for neural reconstruction applications, as the material possesses favorable mechanical property and degradation characteristics. The effect of PGS on Schwann cell metabolic activity, attachment, proliferation, and apoptosis were examined in vitro in comparison with poly(lactide-co-glycolide) (PLGA), a biomaterial widely utilized for tissue engineering applications. The in vivo tissue response to PGS was compared with PLGA implanted juxtaposed to the sciatic nerve; the physical changes in the implant material were measured during the degradation process. PGS had no deleterious effect on Schwann cell metabolic activity, attachment, or proliferation, and did not induce apoptosis; the in vitro effects of PGS were similar to or superior to that of PLGA. In vivo, PGS demonstrated a favorable tissue response profile compared with PLGA, with significantly less inflammation and fibrosis and Without detectable swelling during degradation. PGS is an excellent candidate material for neural reconstruction applications given its lack of in vitro Schwann cell toxicity and minimal in vivo tissue response. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. RP Sundback, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Wellman 625,55 Fruit St, Boston, MA 02114 USA. EM csundback@partners.org OI Wang, Yadong/0000-0003-2067-382X NR 29 TC 199 Z9 210 U1 15 U2 88 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2005 VL 26 IS 27 BP 5454 EP 5464 DI 10.1016/j.biomaterials.2005.02.004 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 926YB UT WOS:000229158500004 PM 15860202 ER PT J AU Wieder, KJ King, KR Thompson, DM Zia, C Yarmush, ML Jayaraman, A AF Wieder, KJ King, KR Thompson, DM Zia, C Yarmush, ML Jayaraman, A TI Optimization of reporter cells for expression profiling in a microfluidic device SO BIOMEDICAL MICRODEVICES LA English DT Article DE living cell array; microfluidics; GFP; NF-kappa B; reporter cell line ID GREEN FLUORESCENT PROTEIN; GENE-EXPRESSION; TRANSIENT TRANSFECTION; OXIDATIVE STRESS; COCULTURES; SYSTEM; ALPHA; ASSAY AB The emergence of green fluorescence protein (GFP) technologies has enabled non-invasive monitoring of cell function and gene expression. GFP-based expression studies are typically performed in traditional single-dish or multi-well formats to monitor a small number of genes or conditions that do not lend well to scaling, high-throughput analysis, or single-cell measurements. We have recently developed a microfluidic device, the Living Cell Array (LCA), for monitoring GFP-based gene expression in a high-throughput manner. Here, we report the optimization of GFP reporter cell characteristics in this microfluidic device for gene expression profiling. A reporter cell line for the transcription factor NF-kappa B was generated and used as the model cell line. Reporter cells were seeded in the LCA and NF-kappa B activated by addition of the cytokine TNF-alpha . Our studies show that the fluorescence kinetics from the reporter cell line in response to both single and repeated TNF-alpha stimulation in the LCA is similar to that observed in standard tissue culture. In addition, our data also indicate that multiple expression waves can be reliably monitored from a small population of reporter cells. Using reporter cell line subcloning and cell cycle synchronization, we demonstrate that the kinetics and magnitude of induced fluorescence in the reporter cell lines can be further improved to maximize the fluorescence readout from reporter cell lines, thereby improving their applicability to live cell expression profiling. Our studies establish some of the important criteria to be considered when using reporter cell lines for dynamic expression profiling in microfluidic devices. C1 Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jayaraman, A (reprint author), Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA. EM arulj@tamu.edu FU NIBIB NIH HHS [P41 EB002503]; PHS HHS [5-R01-GN65474] NR 28 TC 31 Z9 32 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD SEP PY 2005 VL 7 IS 3 BP 213 EP 222 DI 10.1007/s10544-005-3028-3 PG 10 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 955RQ UT WOS:000231245400007 PM 16133809 ER PT J AU Yu, ZF Catalano, PJ AF Yu, ZF Catalano, PJ TI Quantitative risk assessment for multivariate continuous outcomes with application to neurotoxicology: The bivariate case SO BIOMETRICS LA English DT Article DE benchmark dose; dose-response modeling; multiple outcomes; percentile regression ID BENCHMARK-DOSE ESTIMATION; DEVELOPMENTAL TOXICITY; FETAL WEIGHT; RESPONSES; TOXICOLOGY AB The neurotoxic effects of chemical agents are often investigated in controlled studies on rodents, with multiple binary and continuous endpoints routinely collected. One goal is to conduct quantitative risk assessment to determine safe dose levels. Such studies face two major challenges for continuous outcomes. First, characterizing risk and defining a benchmark dose are difficult. Usually associated with an adverse binary event, risk is clearly definable in quantal settings as presence or absence of an event; finding a similar probability scale for continuous outcomes is less clear. Often, an adverse event is defined for continuous outcomes as any value below a specified cutoff level in a distribution assumed normal or log normal. Second, while continuous outcomes are traditionally analyzed separately for such studies, recent literature advocates also using multiple outcomes to assess risk. We propose a method for modeling and quantitative risk assessment for bivariate continuous outcomes that address both difficulties by extending existing percentile regression methods. The model is likelihood based; it allows separate dose-response models for each outcome while accounting for the bivariate correlation and overall characterization of risk. The approach to estimation of a benchmark dose is analogous to that for quantal data without the need to specify arbitrary cutoff values. We illustrate our methods with data from a neurotoxicity study of triethyl tin exposure in rats. C1 Stat Collaborat Inc, Washington, DC 20036 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Yu, ZF (reprint author), Stat Collaborat Inc, 1710 Rhodes Isl Ave,Suite 200, Washington, DC 20036 USA. EM fan-fan@statcollab.com FU NCI NIH HHS [CA48061]; NIEHS NIH HHS [ES06900, T32 ES07142-18] NR 24 TC 5 Z9 5 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2005 VL 61 IS 3 BP 757 EP 766 DI 10.1111/j.1541-0420.2005.00350.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 961VM UT WOS:000231689900012 PM 16135027 ER PT J AU Janoff, DM Peterson, C Mongoue-Tchokote, S Peters, L Beer, TM Wersinger, EM Mori, M Garzotto, M AF Janoff, DM Peterson, C Mongoue-Tchokote, S Peters, L Beer, TM Wersinger, EM Mori, M Garzotto, M TI Clinical outcomes of androgen deprivation as the sole therapy for localized and locally advanced prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate; cancer; androgen deprivation; hormone ablation; treatment ID BILATERAL ORCHIECTOMY; RADICAL PROSTATECTOMY; CURATIVE INTENT; PATIENT AGE; MEN; OSTEOPOROSIS; CARCINOMA; MANAGEMENT; DIAGNOSIS; BLOCKADE AB Objective To characterize the clinical outcomes of androgen deprivation therapy (ADT) as the sole therapy for localized prostate cancer, and to determine independent predictors of disease progression, as recent studies indicate an increasing use of ADT. Patients and Methods The records of all patients with cT1-4NXM0 adenocarcinoma of the prostate treated with ADT as the primary initial therapy at the Portland Veterans Affairs Medical Center between 1993 and 2000 were reviewed. Age, race, Charlson Health Index, family history, prostate-specific antigen (PSA) level, PSA density, digital rectal examination (DRE) findings, Gleason score, and percentage of positive biopsy cores at diagnosis were recorded for 81 patients. Patients had a median (SD range) age of 73 (5.6, 58-84) years, a PSA level of 14.3 (34.6, 1.4-252) ng/mL and tumours were classified as Gleason score <= 5 in 9% of patients, 6 in 31%, 7 in 31% and 8-10 in 30%. Outcomes extracted were PSA progression, PSA nadir, bone fractures, local progression, distant progression and overall survival. Results With a median (range) follow-up of 54 (6-115) months, the incidence of local progression, distant progression, bone fractures, PSA progression, and death were 10%, 7%, 25%, 21% and 41% respectively. The percentage of positive biopsy cores >= 83%, age < 70 years, Gleason score >= 7, abnormal DRE, and PSA nadir >= 0.2 ng/mL were significantly associated with PSA progression by univariate analysis. The multivariate analysis identified age < 70 years (hazard ratio 6.52, 95% confidence interval 2.29-18.55) and Gleason score >= 6 (4.0, 2.0-12.0) as independent risk factors for PSA progression. Conclusions ADT resulted in modest control of localized prostate cancer, but younger patients and those with Gleason >= 6 cancers were at higher risk of treatment failure. Toxicity, principally in the form of bone fractures, was high. C1 Portland Vet Affairs Med Ctr, Urol Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR USA. Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR USA. RP Garzotto, M (reprint author), Portland Vet Affairs Med Ctr, Urol Sect, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM garzotto@ohsu.edu FU NCI NIH HHS [P30 CA69533] NR 26 TC 26 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD SEP PY 2005 VL 96 IS 4 BP 503 EP 507 DI 10.1111/j.1464-410X.2005.05674.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 957QK UT WOS:000231387900011 PM 16104900 ER PT J AU Pontari, MA McNaughton-Collins, M O'Leary, MP Calhoun, EA Jang, T Kusek, JW Landis, JR Knauss, J Litwin, MS AF Pontari, MA McNaughton-Collins, M O'Leary, MP Calhoun, EA Jang, T Kusek, JW Landis, JR Knauss, J Litwin, MS CA CPCRN Study Grp TI A case-control study of risk factors in men with chronic pelvic pain syndrome SO BJU INTERNATIONAL LA English DT Article DE chronic prostatitis; pelvic pain; urethritis; hypertension ID CHRONIC PROSTATITIS; INTERSTITIAL CYSTITIS; PREVALENCE; COHORT AB Objective To compare the demographic, behavioural, clinical and medical history characteristics of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and asymptomatic controls, to identify characteristics that might be associated with this syndrome. Patients and Methods Self-administered epidemiological questionnaires were completed by 463 men with CP/CPPS and 121 asymptomatic age-matched controls. We compared the prevalence of possible risk factors between men with CP/CPPS and controls, using generalized Mantel-Haenszel tests, and developed multivariate predictive models using logistic regression methods, adjusting for clustering by clinical centre within both methods. Results Compared to controls, men with CP/CPPS reported a significantly greater lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008), cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%, P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic, lymphatic or infectious disease (41% vs 20%, P < 0.001). Conclusion A wide range of self-reported medical conditions was associated with CP/CPPS. Further studies are necessary to determine whether they play a role in the pathogenesis of CP/CPPS. C1 Temple Univ, Sch Med, Philadelphia, PA 19140 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Northwestern Univ, Chicago, IL 60611 USA. NIDDKD, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Pontari, MA (reprint author), Temple Univ, Sch Med, 3401 N Broad St,Suite 350 Parkinson Pavil, Philadelphia, PA 19140 USA. EM Pontarm@tuhs.temple.edu RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [U01 DK53730, U01 DK53572, U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53738, U01 DK53746] NR 19 TC 48 Z9 53 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD SEP PY 2005 VL 96 IS 4 BP 559 EP 565 DI 10.1111/j.1464-410X.2005.05684.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 957QK UT WOS:000231387900021 PM 16104910 ER PT J AU Kaplan, LD Lee, JY Ambinder, RF Sparano, JA Cesarman, E Chadburn, A Levine, AM Scadden, DT AF Kaplan, LD Lee, JY Ambinder, RF Sparano, JA Cesarman, E Chadburn, A Levine, AM Scadden, DT TI Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010 SO BLOOD LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; ANTI-CD20 MONOCLONAL-ANTIBODY; B-CELL LYMPHOMA; INDOLENT LYMPHOMA; PERIPHERAL-BLOOD; ELDERLY-PATIENTS; CHEMOTHERAPY; NEUTROPENIA; CYCLOPHOSPHAMIDE; DOXORUBICIN AB The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy results in significant improvement in clinical outcome for individuals with non-HIV-associated aggressive B-cell lymphoma. To assess the potential risks and benefits of the addition of rituximab to CHOP for HIV-associated non-Hodgkin lymphoma (HIV-NHL) 150 patients receiving CHOP for HIV-NHL were randomized (2:1) to receive 375 mg/m(2) rituximab with each chemotherapy cycle (n = 99) or no immunotherapy (n = 50) in a multicenter phase 3 trial. The complete response rate (CR + CRu) was 57.6% for R-CHOP and 47% for CHOP (P =.147). With a median follow-up of 137 weeks, time to progression, progression-free survival, and overall survival times were 125, 45, and 139 weeks, respectively, for R-CHOP and 85, 38, and 110 weeks, respectively, for CHOP (P = not significant, all comparisons). Treatment-related infectious deaths occurred in 14% of patients receiving R-CHOP compared with 2% in the chemotherapy-alone group (P =.035). Of these deaths, 60% occurred in patients with CD4 counts less than 50/mm(3). Progression-free survival was significantly influenced by CD4(+) count (P <.001) and International Prognostic Index score (P =.022), but not bcl-2 status. The addition of rituximab to CHOP in patients with HIV-NHL may be associated with improved tumor responses. However, these benefits may be offset by an increase in infectious deaths, particularly in those individuals with CD4(+) lymphocyte counts less than 50/mm(3). C1 Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA. Univ Alabama, Div Hematol Oncol, Med Stat Sect, Birmingham, AL 35294 USA. Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. Montefiore Med Ctr, Albert Einstein Canc Ctr, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Pathol, New York, NY USA. Univ So Calif, Dept Med, Los Angeles, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA USA. RP Kaplan, LD (reprint author), Univ Calif San Francisco, Div Hematol Oncol, 400 Parnassus Ave,Rm A-502, San Francisco, CA 94143 USA. EM lkaplan@medicine.ucsf.edu FU NCI NIH HHS [U01CA083 035, U01CA070 019, U01CA070 047, U01CA070 054, U01CA070 062, U01CA070 079, U01CA070 080, U01CA070 081, U01CA071 375, U01CA083 038, U01CA083 118, U01CA70 058]; PHS HHS [U01C-A070 072] NR 26 TC 212 Z9 219 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1538 EP 1543 DI 10.1182/blood-2005-04-1437 PG 6 WC Hematology SC Hematology GA 959CR UT WOS:000231495000014 PM 15914552 ER PT J AU Ishikawa, F Yasukawa, M Lyons, B Yoshida, S Miyamoto, T Yoshimoto, G Watanabe, T Akashi, K Shultz, LD Harada, M AF Ishikawa, F Yasukawa, M Lyons, B Yoshida, S Miyamoto, T Yoshimoto, G Watanabe, T Akashi, K Shultz, LD Harada, M TI Development of functional human blood and immune systems in NOD/SCID/IL2 receptor gamma chain(null) mice SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; HUMAN HEMATOLYMPHOID CELLS; ACUTE MYELOID-LEUKEMIA; IL-2 RECEPTOR; BONE-MARROW; SCID MICE; LYMPHOID DEVELOPMENT; CYTOPLASMIC DOMAIN; SIGNALING PATHWAYS AB Here we report that a new nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse line harboring a complete null mutation of the common cytokine receptor gamma chain (NOD/SCID/interleukin 2 receptor [IL2r] gamma(null)) efficiently supports development of functional human hemato-lymphopoiesis. Purified human (h) CD34(+) or hCD34(+)hCD38(-) cord blood (CB) cells were transplanted into NOD/SCID/IL2r gamma(null) newborns via a facial vein. In all recipients injected with 10(5) hCD34(+) or 2 x 10(4) hCD34(+)hCD38(-) CB cells, human hematopoietic cells were reconstituted at approximately 70% of chimerisms. A high percentage of the human hematopoietic cell chimerism persisted for more than 24 weeks after transplantation, and hCD34(+) bone marrow grafts of primary recipients could reconstitute hematopoiesis in secondary NOD/ SCID/IL2r gamma(null) recipients, suggesting that this system can support self-renewal of human hematopoietic stem cells. hCD34(+)hCD38(-) CB cells differentiated into mature blood cells, including myelomonocytes, dendritic cells, erythrocytes, platelets, and lymphocytes. Differentiation into each lineage occurred via developmental intermediates such as common lymphoid progenitors and common myeloid progenitors, recapitulating the steady-state human hematopoiesis. B cells underwent normal class switching, and produced antigen-specific immunoglobulins (Igs). T cells displayed the human leukocyte antigen (HLA)-dependent cytotoxic function. Furthermore, human IgA-secreting B cells were found in the intestinal mucosa, suggesting reconstitution of human mucosal immunity. Thus, the NOD/SCID/IL2r gamma(null) newborn system might be an important experimental model to study the human hemato-lymphoid system. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosystemic Sci, Fukuoka 812, Japan. Ehime Univ, Sch Med, Dept Internal Med 1, Shigenobu, Ehime 79102, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. RIKEN Allergy & Immunol, Yokohama, Kanagawa, Japan. RP Akashi, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,770, Boston, MA 02115 USA. EM koichi_akashi@dfci.harvard.edu RI 石川, 文彦/L-4488-2014 FU NHLBI NIH HHS [HL077642]; NIDDK NIH HHS [DK061320]; PHS HHS [A130389] NR 48 TC 421 Z9 435 U1 4 U2 18 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1565 EP 1573 DI 10.1182/blood-2005-02-0516 PG 9 WC Hematology SC Hematology GA 959CR UT WOS:000231495000018 PM 15920010 ER PT J AU Iwasaki, H Somoza, C Shigematsu, H Duprez, EA Iwasaki-Arai, J Mizuno, S Arinobu, Y Geary, K Zhang, P Dayaram, T Fenyus, ML Elf, S Chan, S Kastner, P Huettner, CS Murray, R Tenen, DG Akashi, K AF Iwasaki, H Somoza, C Shigematsu, H Duprez, EA Iwasaki-Arai, J Mizuno, S Arinobu, Y Geary, K Zhang, P Dayaram, T Fenyus, ML Elf, S Chan, S Kastner, P Huettner, CS Murray, R Tenen, DG Akashi, K TI Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR PU.1; ACUTE MYELOID-LEUKEMIA; COMMON LYMPHOID PROGENITORS; RETAIN LONG-TERM; G-CSF RECEPTOR; B-CELL; LINEAGE COMMITMENT; BONE-MARROW; C/EBP-ALPHA AB The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent "priming" of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show that HSCs express PU.1, and its constitutive expression is necessary for maintenance of the HSC pool in the bone marrow. Bone marrow HSCs disrupted with PU.1 in situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphoid progenitors. PU.1 disruption in granulocyte/monocyte-committed progenitors blocked their maturation but not proliferation, resulting in myeloblast colony formation. PU.1 disruption in common lymphoid progenitors, however, did not prevent their B-cell maturation. In vivo disruption of PU.1 in mature B cells by the CD19-Cre locus did not affect B-cell maturation, and PU.1-deficient mature B cells displayed normal proliferation in response to mitogenic signals including the cross-linking of surface immunoglobulin M (IgM). Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. Arbor Vitae, Sunnyvale, CA USA. Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. EOS Biotech, San Francisco, CA USA. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu RI duprez, estelle/R-2357-2016; OI Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [CA41456, CA72009, CA78045]; NIDDK NIH HHS [DK61320] NR 66 TC 188 Z9 198 U1 3 U2 16 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1590 EP 1600 DI 10.1182/blood-2005-03-0860 PG 11 WC Hematology SC Hematology GA 959CR UT WOS:000231495000021 PM 15914556 ER PT J AU Huang, MT Mason, JC Birdsey, GM Amsellem, V Gerwin, N Haskard, DO Ridley, AJ Randi, AM AF Huang, MT Mason, JC Birdsey, GM Amsellem, V Gerwin, N Haskard, DO Ridley, AJ Randi, AM TI Endothelial intercellular adhesion molecule (ICAM)-2 regulates angiogenesis SO BLOOD LA English DT Article ID NECROSIS-FACTOR (TNF)-ALPHA; CELL-ADHESION; LEUKOCYTE TRANSMIGRATION; BINDING-SITES; CADHERIN GENE; ERM PROTEINS; IFN-GAMMA; TNF-ALPHA; ICAM-2; RAC AB Endothelial junctions maintain endothelial integrity and vascular homeostasis. They modulate cell trafficking into tissues, mediate cell-cell contact and regulate endothelial survival and apoptosis. Junctional adhesion molecules such as vascular endothelial (VE)-cadherin and CD31/platelet endothelial cell adhesion molecule (PECAM) mediate contact between adjacent endothelial cells and regulate leukocyte transmigration and angiogenesis. The leukocyte adhesion molecule intercellular adhesion molecule 2 (ICAM-2) is expressed at the endothelial junctions. In this study we demonstrate that endothelial ICAM-2 also mediates angiogenesis. Using ICAIM-2-deficient mice and ICAM-2-deficient endothelial cells, we show that the lack of ICAM-2 expression results in impaired angiogenesis both in vitro and in vivo. We show that ICAM-2 supports homophilic interaction, and that this may be involved in tube formation. ICAM-2-deficient cells show defective in vitro migration, as well as increased apoptosis in response to serum deprivation, anti-Fas antibody, or staurosporine. ICAM-2 signaling in human umbilical vein endothelial cells (HUVECs) was found to activate the small guanosine triphosphatase (GTPase) Rac, which is required for endothelial tube formation and migration. These data indicate that ICAM-2 may regulate angiogenesis via several mechanisms including survival, cell migration, and Rac activation. Our findings identify a novel pathway regulating angiogenesis through ICAM-2 and a novel mechanism for Rac activation during angiogenesis. C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, BHF Cardiovasc Sci Unit, Eric Bywaters Ctr Vasc Inflammat, London W12 0NN, England. UCL Royal Free & Univ Coll Sch Med, Ludwig Inst Canc Res, London, England. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Randi, AM (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, BHF Cardiovasc Sci Unit, Eric Bywaters Ctr Vasc Inflammat, Du Cane Rd, London W12 0NN, England. EM a.randi@imperial.ac.uk OI Birdsey, Graeme/0000-0002-0981-8672; Ridley, Anne/0000-0001-8186-5708 NR 44 TC 48 Z9 51 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 SEP 1 PY 2005 VL 106 IS 5 BP 1636 EP 1643 DI 10.1182/blood-2004-12-4716 PG 8 WC Hematology SC Hematology GA 959CR UT WOS:000231495000027 PM 15920013 ER PT J AU Zaunders, JJ Munier, ML Kaufmann, DE Ip, S Grey, P Smith, D Ramacciotti, T Quan, D Finlayson, R Kaldor, J Rosenberg, ES Walker, BD Cooper, DA Kelleher, AD AF Zaunders, JJ Munier, ML Kaufmann, DE Ip, S Grey, P Smith, D Ramacciotti, T Quan, D Finlayson, R Kaldor, J Rosenberg, ES Walker, BD Cooper, DA Kelleher, AD CA PHAEDRA Study Team TI Early proliferation of CCR5(+) CD38(+++) antigen-specific CD4(+) Th1 effector cells during primary HIV-1 infection SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CD8(+) T-CELLS; CXC CHEMOKINE RECEPTOR-5; TYPE-1 INFECTION; IN-VIVO; INTERFERON-GAMMA; VIRAL-INFECTION; HELPER-CELLS; GASTROINTESTINAL-TRACT AB We investigated whether HIV-1 antigen-specific CD4(+) T cells expressed the viral coreceptor CCR5 during primary HIV-1 infection (PHI). In the peripheral blood of subjects with very early PHI (< 22 days after onset of symptoms), there was a 10- to 20-fold increase in the proportion of highly activated (CD38(+++).) and proliferating (Ki67(+)) CD4+ T cells that expressed CCR5(+), and were mostly T-cell intracellular antigen-1 (TIA-1)(+)perforin(+)granzyme B+. In the same patient samples, CD4(+) T cells producing interferon (IFN)-gamma in response to HIV group-specific antigen (Gag) peptides were readily detected (median, 0.58%) by intracellular cytokine assay-these cells were again predominantly CD38(+++), Ki-67(+), and TIA-1 (+), as well as Bcl-2(low). On average, 20% of the Gag-specific CD4(+) T cells also expressed interleukin-2 (IL-2) and were CD127 (IL-7R)(+). Taken together, these results suggest that Gag-specific T-helper 1 (Thl) effector cells express CCR5 during the primary response and may include precursors of long-term self-renewing memory cells. However, in PHI subjects with later presentation, antigen-specific CD4(+) T cells could not be readily detected (median, 0.08%), coinciding with a 5-fold lower level of the CCR5(+) CD38(+++) CD4(+) T cells. These results suggest that the antiviral response to HIV-1 infection includes highly activated CCR5(+)CD4(+) cytotoxic effector cells, which are susceptible to both apoptosis and cytopathic infection with HIV-1, and rapidly decline. C1 St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Holdsworth House Gen Practice, Sydney, NSW, Australia. Taylor Sq Private Clin, Sydney, NSW, Australia. RP Zaunders, JJ (reprint author), St Vincents Hosp, Ctr Immunol, Victoria St, Darlinghurst, NSW 2010, Australia. EM j.zaunders@cfi.unsw.edu.au RI Zaunders, John/J-6553-2012; Kaldor, John /D-4545-2011 OI Zaunders, John/0000-0002-5912-5989; NR 83 TC 43 Z9 46 U1 2 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 SEP 1 PY 2005 VL 106 IS 5 BP 1660 EP 1667 DI 10.1182/blood-2005-01-0206 PG 8 WC Hematology SC Hematology GA 959CR UT WOS:000231495000030 PM 15905189 ER PT J AU Haining, WN Neuberg, DS Keczkemethy, HL Evans, JW Rivoli, S Gelman, R Rosenblatt, HM Shearer, WT Guenaga, J Douek, DC Silverman, LB Sallan, SE Guinan, EC Nadler, LM AF Haining, WN Neuberg, DS Keczkemethy, HL Evans, JW Rivoli, S Gelman, R Rosenblatt, HM Shearer, WT Guenaga, J Douek, DC Silverman, LB Sallan, SE Guinan, EC Nadler, LM TI Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; KERATINOCYTE GROWTH-FACTOR; INTENSIVE CHEMOTHERAPY; IN-VIVO; VIRUS-INFECTION; RAPID TURNOVER; HIV-INFECTION; RECONSTITUTION; CD8(+); ADULTS AB Despite profound T-cell immunodeficiency, most patients treated with chemotherapy do not succumb to infection. The basis for residual protective immunity in lymphopenic patients is not known. We prospectively measured T-cell numbers, thymopoiesis, and T-cell memory in 73 children undergoing a 2-year chemotherapy regimen for acute lymphoblastic leukemia (ALL) and compared them to an age-matched cohort of 805 healthy children. Most patients had profound defects in CD4 and CD8 T-cell numbers at diagnosis that did not recover during the 2 years of therapy. Thymic output and the fraction of naive T cells were significantly lower than in healthy controls. However, the remaining T-cell compartment was enriched for antigen-experienced, memory T cells defined both by phenotype and by function. This relative sparing of T-cell memory may, in part, account for the maintenance of protective immunity in lymphopenic Patients treated for ALL. Moreover, because the memory T-cell compartment is least affected by ALL and its treatment, strategies to induce immunity to pathogens or tumor antigens in cancer patients may be most successful if they seek to expand preexisting memory T cells. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Texas Childrens Hosp, Houston, TX 77030 USA. NIH, Vaccine Res Ctr, Bethesda, MD USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Haining, WN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM nicholas_haining@dfci.harvard.edu FU NCI NIH HHS [P01CA68 484]; NHLBI NIH HHS [K08HL72 750] NR 46 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2005 VL 106 IS 5 BP 1749 EP 1754 DI 10.1182/blood-2005-03-1082 PG 6 WC Hematology SC Hematology GA 959CR UT WOS:000231495000041 PM 15920008 ER PT J AU Ishitsuka, K Hideshima, T Hamasaki, M Raje, N Kumar, S Hideshima, H Shiraishi, N Yasui, H Roccaro, AM Richardson, P Podar, K Le Gouill, S Chauhan, D Tamura, K Arbiser, J Anderson, KC AF Ishitsuka, K Hideshima, T Hamasaki, M Raje, N Kumar, S Hideshima, H Shiraishi, N Yasui, H Roccaro, AM Richardson, P Podar, K Le Gouill, S Chauhan, D Tamura, K Arbiser, J Anderson, KC TI Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis SO BLOOD LA English DT Article ID PROTEASOME INHIBITOR PS-341; PROGRAMMED CELL-DEATH; HEAT-SHOCK PROTEINS; BCL-X-L; SERINE-PROTEASE; THERAPEUTIC APPLICATIONS; MAGNOLIA-OFFICINALIS; DNA FRAGMENTATION; DOWN-REGULATION; IN-VITRO AB Honokiol (HNK) is an active component purified from magnolia, a plant used in traditional Chinese and Japanese medicine. Here we show that HNK significantly induces cytotoxicity in human multiple myeloma (MM) cell lines and tumor cells from patients with relapsed refractory MM. Neither coculture with bone marrow stromal cells nor cytokines (interleukin-6 and insulin-like growth factor-1) protect against HNK-induced cytotoxicity. Although activation of caspases 3, 7, 8, and 9 is triggered by HNK, the pan-caspase inhibitor z-VAD-fmk does not abrogate HNK-induced apoptosis. Importantly, release of an executioner of caspase-independent apoptosis, apoptosis-inducing factor (AIF), from mitochondria is induced by HNK treatment. HNK induces apoptosis in the SU-DHL4 cell line, which has low levels of caspase 3 and 8 associated with resistance to both conventional and novel drugs. These results suggest that HNK induces apoptosis via both caspase-dependent and -independent pathways. Furthermore, HNK enhances MM cell cytotoxicity and apoptosis induced by bortezomib. In addition to its direct cytotoxicity to MM cells, HNK also represses tube formation by endothelial cells, suggesting that HNK inhibits neovascurization in the bone marrow microenvironment. Taken together, our results provide the preclinical rationale for clinical protocols of HNK to improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Fukuoka Univ, Dept Internal Med 1, Fukuoka 81401, Japan. Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. RP Anderson, KC (reprint author), 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 OI Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [IP50 CA10 070-01, P0-1 CA78 378, R0-1 CA 50 947]; NIAMS NIH HHS [R01 AR 47 901] NR 51 TC 109 Z9 121 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 SEP 1 PY 2005 VL 106 IS 5 BP 1794 EP 1800 DI 10.1182/blood-2005-01-0346 PG 7 WC Hematology SC Hematology GA 959CR UT WOS:000231495000047 PM 15870175 ER PT J AU Quigley, JG Gazda, H Yang, ZT Ball, S Sieff, CA Abkowitz, JL AF Quigley, JG Gazda, H Yang, ZT Ball, S Sieff, CA Abkowitz, JL TI Investigation of a putative role for FLVCR, a cytoplasmic heme exporter, in Diamond-Blackfan anemia SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Diamond-Blackfan anemia; FLVCR; heme export ID VIRUS SUBGROUP-C; RED-CELL APLASIA; RECEPTOR; RETROVIRUS; EXPRESSION; KINETICS; GENE AB Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell aplasia. Previous studies indicate that mutations of a gene on chromosome 19q13.2, which encodes a ribosomal protein, are responsible for 25% of cases. Recent investigations suggest both the presence of a second candidate region on chromosome 8p and non-19q, non-8p disease. In linkage analysis studies of 28 multiplex DBA families, we identified 8 families with disease linkage to chromosome 1q31. In 4 families, the disease linked exclusively to 1q31. Here, we report that the FLVCR gene on 1q31, which encodes a cytoplasmic heme exporter associated with red cell aplasia in cats, is not involved in DBA in these families. (c) 2005 Published by Elsevier Inc. C1 Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. Dana Farber Canc Inst, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Genet, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. St George Hosp, Sch Med, Dept Hematol, London, England. RP Abkowitz, JL (reprint author), Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. EM janabk@u.washington.edu OI quigley, john/0000-0003-3116-4545 FU NHLBI NIH HHS [R01 HL31823] NR 15 TC 16 Z9 16 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP-OCT PY 2005 VL 35 IS 2 BP 189 EP 192 DI 10.1016/j.bcmd.2005.01.005 PG 4 WC Hematology SC Hematology GA 967BS UT WOS:000232067100017 PM 15996880 ER PT J AU Elkin, EB Weinstein, MC Kuntz, KM Bunnell, CA Weeks, JC AF Elkin, EB Weinstein, MC Kuntz, KM Bunnell, CA Weeks, JC TI Adjuvant ovarian suppression versus chemotherapy for premenopausal, hormone-responsive breast cancer: Quality of life and efficacy tradeoffs SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 19-23, 2002 CL BALTIMORE, MD SP Soc Med Decis Making DE adjuvant therapy; breast cancer; chemotherapy; decision analysis; ovarian suppression; quality of life ID COOPERATIVE-ONCOLOGY-GROUP; ISOLATED LOCOREGIONAL RECURRENCE; INTERNATIONAL CONSENSUS PANEL; RANDOMIZED-TRIAL; RESEARCH-ASSOCIATION; CONSERVING SURGERY; RADIATION-THERAPY; NATURAL MENOPAUSE; DECISION-ANALYSIS; PLUS TAMOXIFEN AB Purpose. Recent clinical trials suggest that adjuvant ovarian suppression may be an equally effective and less toxic alternative to systemic chemotherapy in premenopausal women with hormone-responsive breast cancer. We used a decision-analytic framework to evaluate tradeoffs between efficacy and quality of life in the choice between these treatments. Patients and methods. We used a Markov state-transition model to simulate clinical practice in a cohort of 40-year-old premenopausal women with newly diagnosed, hormone-responsive early breast cancer. We assessed three adjuvant treatments: chemotherapy, surgical ovarian suppression, and medical ovarian suppression. Outcomes were recurrence-free, overall, and quality-adjusted survival. Quality-adjusted survival reflected effects of cancer, treatment-related side effects, and menopausal symptoms. Results. Assuming equal efficacy, ovarian suppression was superior to chemotherapy when the relative utility of chemotherapy side effects compared with ovarian suppression side effects was less than 0.95. Results were sensitive to assumptions about the likelihood, duration and consequences of treatment-induced menopause. Treatment choice was affected by a 7% proportional increase in the efficacy of one therapy relative to the others, independent of other factors. Conclusion. If adjuvant chemotherapy and ovarian suppression have similar efficacy, then there may be a subgroup of women for whom quality-of-life considerations dominate the choice of treatment. However, small differences in the relative efficacy of these therapies have a substantial impact on treatment choice, regardless of side effects and menopausal transitions. C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Elkin, EB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave,Box 44, New York, NY 10021 USA. EM elkine@mskcc.org NR 62 TC 2 Z9 4 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2005 VL 93 IS 1 BP 25 EP 34 DI 10.1007/s10549-005-3380-2 PG 10 WC Oncology SC Oncology GA 968CP UT WOS:000232139800004 PM 16184455 ER PT J AU Gacci, M Orzalesi, L Distante, V Nesi, G Vezzosi, V Livi, L Mungai, V Romagnani, P Eisner, B Carini, M AF Gacci, M Orzalesi, L Distante, V Nesi, G Vezzosi, V Livi, L Mungai, V Romagnani, P Eisner, B Carini, M TI Renal cell carcinoma metastatic to the breast and breast cancer metastatic to the kidney: Two rare solitary metastases SO BREAST JOURNAL LA English DT Editorial Material C1 Univ Florence, Dept Urol, I-50132 Florence, Italy. Univ Florence, Dept Gen Surg, I-50132 Florence, Italy. Univ Florence, Dept Pathol, I-50132 Florence, Italy. Univ Florence, Dept Radiotherapy, I-50132 Florence, Italy. Univ Florence, Dept Clin Physiopathol, I-50132 Florence, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gacci, M (reprint author), Univ Florence, Dept Urol, Via Masaccio 102, I-50132 Florence, Italy. EM maurogacci@yahoo.it RI Romagnani, Paola/A-4309-2008; livi, lorenzo/K-8934-2016; OI Romagnani, Paola/0000-0002-1774-8088; livi, lorenzo/0000-0002-7755-9422; Gacci, Mauro/0000-0001-7877-221X NR 0 TC 2 Z9 2 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD SEP-OCT PY 2005 VL 11 IS 5 BP 351 EP 352 DI 10.1111/j.1075-122X.2005.00057.x PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 014OP UT WOS:000235489800010 PM 16174157 ER PT J AU Waldman, KL Debakey, ME AF Waldman, KL Debakey, ME TI Cognitive-bebavioral treatment of obesity: A clinician's guide SO BULLETIN OF THE MENNINGER CLINIC LA English DT Book Review C1 Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. RP Waldman, KL (reprint author), Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD FAL PY 2005 VL 69 IS 4 BP 343 EP 344 PG 2 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 996CY UT WOS:000234153200009 ER PT J AU Chow, BJW Hoffmann, U Nieman, K AF Chow, BJW Hoffmann, U Nieman, K TI Computed tomographic coronary angiography: An alternative to invasive coronary angiography SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Review DE angiography; coronary disease; diagnosis; imaging; tomography ID MULTIDETECTOR-ROW CT; CONGENITAL HEART-DISEASE; ARTERY-BYPASS GRAFTS; ELECTRON-BEAM CT; MAGNETIC-RESONANCE; NONINVASIVE VISUALIZATION; MYOCARDIAL-INFARCTION; DIAGNOSTIC-ACCURACY; STENT PATENCY; STENOSES AB Over the past decade, enormous progress has been made in the technology of computed tomography (CT) imaging. Substantial improvements in spatial resolution, temporal resolution, hardware and software now permit imaging of the entire coronary artery tree within a single breath-hold. Several studies have demonstrated a high sensitivity and specificity for the detection of significant coronary artery stenoses. In addition to imaging of the native coronary arteries, CT angiography may also be used to assess arterial and venous bypass grafts, and to detect the presence and composition of atherosclerotic plaque. Because CT angiography images are acquired with electrocardiogram gating, the data sets permit the assessment of left ventricular function (ejection fraction and regional wall motion), left ventricular volumes and, potentially, myocardial perfusion at no extra cost. The practical advantages of CT angiography (in regard to safety and cost) along with its future anticipated advancements make it an attractive alternative to diagnostic coronary angiography. C1 Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Chow, BJW (reprint author), Univ Ottawa, Inst Heart, 40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM bchow@ottawaheart.ca NR 50 TC 20 Z9 21 U1 1 U2 2 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD SEP PY 2005 VL 21 IS 11 BP 933 EP 940 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 965HN UT WOS:000231941300005 PM 16239977 ER PT J AU Carlsson, H Yhr, M Petersson, S Collins, N Polyak, K Enerback, C AF Carlsson, H Yhr, M Petersson, S Collins, N Polyak, K Enerback, C TI Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive oxygen species and is downregulated by Bcl-2 and antioxidants SO CANCER BIOLOGY & THERAPY LA English DT Article DE psoriasin; calgranulin-B; ROS; Bcl-2; antioxidants ID NF-KAPPA-B; CALCIUM-BINDING PROTEINS; HUMAN KERATINOCYTES; OXIDATIVE STRESS; CELL-DEATH; IN-VIVO; TRANSCRIPTION FACTORS; BREAST-CANCER; NORMAL SKIN; EXPRESSION AB S-100 proteins are calcium-binding proteins with important growth regulatory functions. Of these proteins, psoriasin and calgranulin-B have been shown to be highly upregulated in ductal carcinoma in situ (DCIS) of the breast and in psoriasis. The purpose of this study was to further elucidate the functional relevance of the overexpression of these two S-100 proteins in psoriasis and DCIS. We report the induction of both proteins by reactive oxygen species, phorbol ester TPA, and the induction of psoriasin in response to the PI3K inhibitor wortmannin. We also demonstrate that Bcl-2 overexpression represses the induction of psoriasin and calgranulin-B under these different conditions. The same effect was obtained with the antioxidant NAC, which indicates that the suppression of psoriasin and calgranulin-B induction is mediated by the antioxidant function of Bcl-2. Furthermore, we demonstrate that overexpression of a dominant negative IKK beta also inhibits the induction of psoriasin suggesting that the NF kappa B pathway is involved in the induction of this protein. Also, we found NF kappa B responsive DNA elements in the upstream promoter region of psoriasin. MCF10A cells with a stable retroviral overexpression of psoriasin were significantly more resistant to H2O2-induced cell death than control cells further supporting the hypothesis that these S-100 proteins may play a role in oxidative stress response. C1 Sahlgrens Univ Hosp, Dept Clin Genet, SE-41685 Gothenburg, Sweden. Sahlgrens Univ Hosp, Dept Dermatol, SE-41685 Gothenburg, Sweden. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Enerback, C (reprint author), Sahlgrens Univ Hosp, Dept Clin Genet, SE-41685 Gothenburg, Sweden. EM charlotta.enerback@clingen.gu.se NR 48 TC 24 Z9 27 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP PY 2005 VL 4 IS 9 BP 998 EP 1005 PG 8 WC Oncology SC Oncology GA 022GM UT WOS:000236043400023 PM 16082188 ER PT J AU Stanger, BZ Stiles, B Lauwers, GY Bardeesy, N Mendoza, M Wang, Y Greenwood, A Cheng, KH McLaughlin, M Brown, D DePinho, RA Wu, H Melton, DA Dor, Y AF Stanger, BZ Stiles, B Lauwers, GY Bardeesy, N Mendoza, M Wang, Y Greenwood, A Cheng, KH McLaughlin, M Brown, D DePinho, RA Wu, H Melton, DA Dor, Y TI Pten constrains centroacinar cell expansion and malignant transformation in the pancreas SO CANCER CELL LA English DT Article ID GROWTH-FACTOR-ALPHA; NF-KAPPA-B; TRANSGENIC MICE; CANCER CELLS; TGF-ALPHA; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; GENETIC ALTERATIONS; EXOCRINE PANCREAS; DOUBLE REPORTER AB To determine the role of the phosphatidylinositol 3-kinase (P13-K) pathway in pancreas development, we generated a pancreas-specific knockout of Pten, a negative regulator of P13-K signaling. Knockout mice display progressive replacement of the acinar pancreas with highly proliferative ductal structures that contain abundant mucins and express Pdx1 and Hes1, two markers of pancreatic progenitor cells. Moreover, a fraction of these mice develop ductal malignancy. We provide evidence that ductal metaplasia results from the expansion of centroacinar cells rather than transdifferentiation of acinar cells. These results indicate that Pten actively maintains the balance between different cell types in the adult pancreas and that misregulation of the P13-K pathway in centroacinar cells may contribute to the initiation of pancreatic carcinoma in vivo. C1 Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Patho Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Hebrew Univ Jerusalem, Sch Med, Dept Cellular Biochem & Human Genet, IL-91120 Jerusalem, Israel. RP Dor, Y (reprint author), Harvard Univ, Howard Hughes Med Inst, 7 Divin Ave, Cambridge, MA 02138 USA. EM dor@md.huji.ac.il RI Dor, Yuval/C-2405-2011 FU NIDDK NIH HHS [K08 DK064136] NR 59 TC 177 Z9 184 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD SEP PY 2005 VL 8 IS 3 BP 185 EP 195 DI 10.1016/j.ccr.2005.07.015 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 968YP UT WOS:000232199900006 PM 16169464 ER PT J AU Murphy, KT Wardak, A Beckett, MA Lopez, CA Mehta, N Kimchi, E Salloum, RM Jaskowiak, NT Posner, MC Ohno, T Kufe, DW Weichselbaum, RR Mauceri, HJ AF Murphy, KT Wardak, A Beckett, MA Lopez, CA Mehta, N Kimchi, E Salloum, RM Jaskowiak, NT Posner, MC Ohno, T Kufe, DW Weichselbaum, RR Mauceri, HJ TI Forphenicinol enhances the antitumor effects of cyclophosphamide in a model of squamous cell carcinoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE forphenicinol; cyclophosphamide; ionizing radiation; tumor growth ID MOLECULAR-WEIGHT IMMUNOMODIFIER; IONIZING-RADIATION; COMBINATION; FIBROSARCOMA; ANGIOSTATIN; THERAPY; GROWTH; TUMORS; METH AB We examined the interaction between forphenicinol (FPL) and cyclophosphamide (CPA) or ionizing radiation (IR) on the growth of murine squamous cell carcinoma tumors SCCVII. Primary tumors were established in C3H mice by injecting SCCVII tumor cells subcutaneously into the right hind limb. FPL (100 mg/ kg for 8 days) and/or CPA (25 mg/kg twice) were administered by intraperitoneal injection. Tumors were irradiated to a total dose of 40 Gy (eight 5-Gy fractions). SCCVII tumor growth was inhibited by FPL (P=0.054), IR (P=0.003) and CPA (P<0.001) compared with control. The combination of FPL and CPA inhibited tumor growth additively compared with either treatment alone in both small- and large-volume tumors. FPL did not significantly enhance the antitumor effects of IR, however, when CPA+FPL were combined with IR, significant tumor growth inhibition was observed compared with FPL alone (P<0.001), CPA alone (P=0.002) and IR alone (P=0.002). Due to its low toxicity profile, FPL may be combined with CPA, IR and other cytotoxic therapies to potentially enhance the therapeutic ratio. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Jikei Univ, Sch Med, Inst DNA Med, Tokyo, Japan. RP Mauceri, HJ (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC1105, Chicago, IL 60637 USA. EM hmauceri@rover.uchicago.edu NR 17 TC 3 Z9 3 U1 0 U2 0 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 SEP PY 2005 VL 56 IS 3 BP 317 EP 321 DI 10.1007/s00280-004-0986-8 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 949AR UT WOS:000230757800012 PM 15887016 ER PT J AU Schernhammer, ES Hu, FB Giovannucci, E Michaud, DS Colditz, GA Stampfer, MJ Fuchs, CS AF Schernhammer, ES Hu, FB Giovannucci, E Michaud, DS Colditz, GA Stampfer, MJ Fuchs, CS TI Sugar-sweetened soft drink consumption and risk of pancreatic cancer in two prospective cohorts SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CORONARY-HEART-DISEASE; NATIONAL DEATH INDEX; MIDDLE-AGED WOMEN; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; NUTRIENT INTAKE; PLASMA-GLUCOSE; GLYCEMIC LOAD; QUESTIONNAIRE; MORTALITY AB Background: A history of diabetes mellitus and a diet high in glycemic load are both potential risk factors for pancreatic cancer. Sugar-sweetened soft drinks are a prevalent source of readily absorbable sugars and have been associated with an increased risk of obesity and diabetes. We investigated whether higher consumption of sugar-sweetened soft drinks increases the risk of pancreatic cancer. Methods: We examined the relation between consumption of sugar-sweetened soft drinks and the development of pancreatic cancer in the Nurses' Health Study and the Health Professionals Follow-up Study. Among 88,794 women and 49,364 men without cancer at baseline, we documented 379 cases of pancreatic cancer during up to 20 years of follow-up. Soft drink consumption was first assessed at baseline (1980 for the women, 1986 for the men) and updated periodically thereafter. Results: Compared with participants who largely abstained from sugar-sweetened soft drinks, those who consumed more than three sugar-sweetened soft drinks weekly expe-rienced overall a multivariate relative risk (RR) of pancreatic cancer of 1.13 [95% confidence interval (95% CI), 0.81-1.58; P for trend = 0.471. Women in the highest category of sugarsweetened soft drink intake did experience a significant increase in risk (RR, 1.57; 95% CI, 1.02-2.41; P for trend = 0.05), whereas there was no association between sweetened soft drink intake and pancreatic cancer among men. Among women, the risk associated with higher sugar-sweetened soft drink was limited to those with elevated body mass index (> 25 kg/m(2); RR, 1.89; 95% CI, 0.96-3.72) or with low physical activity (RR, 2.02; 95% Cl, 1.06-3.85). In contrast, consumption of diet soft drinks was not associated with an elevated pancreatic cancer risk in either cohort. Conclusion: Although soft drink consumption did not influence pancreatic cancer risk among men, consumption of sugar-sweetened soft drinks may be associated with a modest but significant increase in risk among women who have an underlying degree of insulin resistance. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 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, Ctr Canc Prevent, Boston, MA USA. Harvard Univ, Program Epidemiol, Boston, MA USA. Harvard Univ, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schernhammer@channing.harvard.edu RI Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 40356, CA 55075, CA 86102, CA 87969, CA/ES62984] NR 32 TC 55 Z9 57 U1 0 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2098 EP 2105 DI 10.1158/1055-9965.EPI-05-0059 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400008 PM 16172216 ER PT J AU Wang, V Li, C Lin, M Welch, W Bell, D Wong, YF Berkowitz, R Mok, SC Bandera, CA AF Wang, V Li, C Lin, M Welch, W Bell, D Wong, YF Berkowitz, R Mok, SC Bandera, CA TI Ovarian cancer is a heterogeneous disease SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; EXPRESSION; P53; P16; PCR AB The purpose of this study was to systematically evaluate the molecular profiles of different histologic types of epithelial ovarian cancer before the disease has metastasized beyond the ovary. Stage 1 epithelial ovarian cancers were chosen for analysis of early genetic events associated with different cell types. Allelotyping of 47 cases was performed using 224 polymorphic markers, Analysis with Fisher's exact test found markers specific for grade 3 tumors and clear cell histology. Hierarchal clustering analysis using dChip software revealed that the pattern of allele loss in eight regions on four chromosomes led to grouping of grade 3 tumors, endometrioid (grades 1 and 2) tumors, and clear cell tumors. We conclude that ovarian cancer is a heterogeneous disease in which histologic phenotypes correlate with distinct genetic patterns. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr,Div Gynecol Oncol, Brigham & Womens Hosp,Dept Obstet Gynecol & Repro, Boston, MA 02115 USA. Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. China Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. RP Bandera, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr,Div Gynecol Oncol, Brigham & Womens Hosp,Dept Obstet Gynecol & Repro, Boston, MA 02115 USA. EM cbandera@wihri.org FU NCI NIH HHS [R33CA103595, P50CA165009, CA86381]; NICHD NIH HHS [K12-HD01265] NR 16 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 2005 VL 161 IS 2 BP 170 EP 173 DI 10.1016/j.cancergencyto.2004.12.014 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 961VD UT WOS:000231689000012 PM 16102589 ER PT J AU Allen, AM Prosnitz, RG Ten Haken, RK Normolle, DP Yu, XL Zhou, SM Marsh, R Marks, LB Pierce, LJ AF Allen, AM Prosnitz, RG Ten Haken, RK Normolle, DP Yu, XL Zhou, SM Marsh, R Marks, LB Pierce, LJ TI Body mass index predicts the incidence of radiation pneumonitis in breast cancer patients SO CANCER JOURNAL LA English DT Article DE breast cancer; radiation pneumonitis; body mass index ID HIGH-DOSE CHEMOTHERAPY; AXILLARY LYMPH-NODES; INTENSITY-MODULATED RADIOTHERAPY; STEM-CELL SUPPORT; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; VOLUME HISTOGRAM; LUNG FIBROSIS; CHEST-WALL; STAGE-II AB In patients receiving breast radiotherapy, the risk of radiation pneumonitis has been associated with the volume of irradiated lung, and concomitant methotrexate, paclitaxel, and tamoxifen therapy. Many of the studies of radiation pneumonitis are based on estimates of pulmonary risk using central lung distance that is calculated using two-dimensional techniques. With the treatment of internal mammary nodes and three-dimensional treatment planning for breast cancer becoming increasingly more common, there is a need to further consider the impact of dose-volume metrics in assessing radiation pneumonitis risk. We herein present a case control study assessing the impact of clinical and dose-volume metrics on the development of radiation pneumonitis in patients receiving sequential chemotherapy and local-regional radiotherapy. C1 Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Duke Univ, Dept Biostat, Durham, NC USA. RP Allen, AM (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02215 USA. EM aallen@lroc.harvard.edu OI Normolle, Daniel/0000-0001-8675-5014 NR 54 TC 8 Z9 8 U1 0 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 SEP-OCT PY 2005 VL 11 IS 5 BP 390 EP 398 DI 10.1097/00130404-200509000-00006 PG 9 WC Oncology SC Oncology GA 975PX UT WOS:000232675500006 PM 16267908 ER PT J AU Johnson, BE Janne, PA AF Johnson, BE Janne, PA TI Epidermal growth factor receptor mutations in patients with non-small cell lung cancer SO CANCER RESEARCH LA English DT Review ID EGFR MUTATIONS; ACQUIRED-RESISTANCE; GENE-MUTATIONS; GEFITINIB; SENSITIVITY; ERLOTINIB; KINASE; RESPONSIVENESS; INHIBITORS; SURVIVAL AB A year has passed since mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) were discovered in patients with non-small cell lung cancer (NSCLC) who had dramatic clinical responses to treatment with gefitinib. Additional laboratory and clinical studies have provided further insight into the biological impact of EGFR mutations in cell culture experiments and in patients with NSCLC. In vitro characterizations of NSCLC cell lines and host cell lines transfected with these mutant and wild-type EGFR show that most cell lines with mutated EGFR are growth-inhibited by 10 to 100-fold lower concentrations of gefitinib and erlotinib compared with wild-type EGFR. NSCLC lines with mutations of the EGFR treated with concentrations of gefitinib and erlotinib that are achievable in the plasma undergo apoptosis rather than growth arrest. Retrospective studies of patients with NSCLC-treated gefitinib have reported a close association between EGFR mutations, increased chance of clinical response and longer survival. This review will provide information on the impact of EGFR mutations on gefitinib and erlotinib treatment by in vitro experiments, the outcome of NSCLC patients with these mutations when treated with gefitinib and erlotinib, and the subsets of patients with NSCLC in whom these mutations arise. C1 Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. EM BEJohnson@Partners.org NR 27 TC 92 Z9 99 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7525 EP 7529 DI 10.1158/0008-5472.CAN-05-1257 PG 5 WC Oncology SC Oncology GA 961JX UT WOS:000231659500001 PM 16140912 ER PT J AU Wang, A Li, CJ Reddy, PV Pardee, AB AF Wang, A Li, CJ Reddy, PV Pardee, AB TI Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR E2F-1; DNA-DAMAGE; S-PHASE; POLY(ADP-RIBOSE) POLYMERASE; BETA-LAPACHONE; CELL-DEATH; RETINOBLASTOMA PROTEIN; INDUCED APOPTOSIS; MAMMALIAN-CELLS; PROSTATE-CANCER AB We propose that the lethality of commonly used anticancer drugs, e.g., methotrexate and cis-platinum are due, at least in part, to an increase of the E217-I-mediated apoptotic cascade. The drugs directly or indirectly decrease deoxynucleoside triphosphates. The E2F family acts to provide control of S phase by transcribing genes required for deoxynucleoside triphosphate and DNA synthesis. Thus, a mechanism for control of E2F-1 is essential, a signal safeguarding against aberrant or uncontrolled cell proliferation. We have proposed a feedback control by NTPs that down-regulates F2F-1. Here, we provide evidence in support of this hypothesis. C1 Dana Farber Canc Inst, Dept Cell Growth, Boston, MA 02115 USA. ArQule Inc, ArQule Biomed Inst, Woburn, MA USA. Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, Dept Cell Growth, D-810,44 Binney St, Boston, MA 02115 USA. EM arthur_pardee@dfci.harvard.edu FU NIDDK NIH HHS [DK57864] NR 74 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7809 EP 7814 DI 10.1158/0008-5472.CAN-05-0888 PG 6 WC Oncology SC Oncology GA 961JX UT WOS:000231659500038 PM 16140949 ER PT J AU Xu, K Guidez, F Glasow, A Chung, D Petrie, K Stegmaier, K Wang, KK Zhang, J Jing, Y Zelent, A Waxman, S AF Xu, K Guidez, F Glasow, A Chung, D Petrie, K Stegmaier, K Wang, KK Zhang, J Jing, Y Zelent, A Waxman, S TI Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; PLZF-RAR-ALPHA; HISTONE DEACETYLASE; MOUSE DEVELOPMENT; SMRT COREPRESSOR; ACTIVATION; PROTEIN; PML; PHOSPHORYLATION; CYTOTOXICITY AB Differentiation induction is an effective therapy for acute promyelocytic leukemia (APL), which dramatically responds to all-trans-retinoic acid (ATRA). Recent studies have indicated that combinatorial use of retinoid and nonretinoid compounds, such as histone deacetylase inhibitors, arsenics, and PKA agonists, has higher therapeutic value in this disease and potentially in other malignancies. In a screen of 370 compounds, we identified benzodithiophene analogues as potent enhancers of ATRA-induced APL cell differentiation. These effects were not associated with changes in global histone acetylation and, for the most potent compounds, were exerted at very low nanomolar concentrations, and were paralleled by enhancement of some, but not all, ATRA-modulated gene expressions. Investigating the mechanism underlying the effects of these drugs on ATRA-induced APL cell differentiation, we have shown that benzodithiophenes enhance ATRA-mediated dissociation and association of corepressor N-CoR and coactivator p300 acetyltransferase, respectively, with retinoic acid receptor (RAR) alpha proteins. These data suggest that benzodithiophenes act at the level of receptor activation, possibly by affecting posttranslational modification of the receptor (and/or coregulators), thus leading to an enhancement in ATRA-mediated effects on gene expression and APL cell differentiation. Given the specificities of these low benzodithiophene concentrations for PNM-RAR alpha and RAR alpha, these drugs may be useful for combinatorial differentiation therapy of APL and possibly other acute myelogenous leukemia subtypes in which the overall ATRA signaling is suppressed. C1 Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Inst Canc Res, Sect Hemato Oncol, London SW3 6JB, England. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Shanghai Med Univ 2, Ruijin Hosp, State Key Lab Med Genom, Shanghai, Peoples R China. Chinese Acad Sci, Shanghai Inst Biol Sci, Hlth Sci Ctr, Shanghai, Peoples R China. RP Waxman, S (reprint author), Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. EM samuel.waxman@mssm.edu RI Zelent, Arthur/B-3532-2009; Guidez, Fabien/B-3750-2009; Petrie, Kevin/I-7115-2015 OI Petrie, Kevin/0000-0002-9805-9152 NR 46 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7856 EP 7865 DI 10.1158/0008-5472.CAN-05-1056 PG 10 WC Oncology SC Oncology GA 961JX UT WOS:000231659500044 PM 16140955 ER PT J AU Altun, M Galardy, PJ Shringarpure, R Hideshima, T LeBlanc, R Anderson, KC Ploegh, HL Kessler, BM AF Altun, M Galardy, PJ Shringarpure, R Hideshima, T LeBlanc, R Anderson, KC Ploegh, HL Kessler, BM TI Effects of PS-341 on the activity and composition of proteasomes in multiple myeloma cells SO CANCER RESEARCH LA English DT Article ID MHC-CLASS-I; INHIBITOR PS-341; ANTIGEN PRESENTATION; SIGNALING CASCADES; GROWTH; CANCER; CYTOTOXICITY; BORTEZOMIB; THERAPIES; TARGET AB Multiple myeloma is a B-cell malignancy for which no curative therapies exist to date, despite enormous research efforts. The remarkable activity of the proteasome inhibitor bortezomib (PS-341, Velcade) observed in clinical trials of patients with relapsed refractory myeloma has led to investigations of the role of the ubiquitin-proteasome pathway in the pathogenesis of myeloma. Here we report a biochemical analysis of proteasome activity and composition in myeloma cells exposed to PS-341 in the presence or absence of cytokines present in the bone marrow milieu. We observed that the myeloma cell lines MMLS, RPMI8226, and U266 contain active immunoproteasomes, the amount of which is enhanced by IFN-gamma and tumor necrosis factor-alpha. Using a radiolabeled active site-directed probe specific for proteasome catalytic subunits, we show that PS-341 targets the 5 and 01 subunits in a concentration-dependent manner. Furthermore, PS-341 also targeted the corresponding catalytic subunits of the immunoproteasome, beta 5i and beta 1i, respectively. These data suggest that PS-341 targets both normal and immunoproteasome species to a similar extent in myeloma cells. C1 Univ Oxford, Ctr Cellular & Mol Physiol, Nuffield Dept Clin Med, Oxford OX3 7BN, England. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Childrens Hosp, Program Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, Boston, MA 02115 USA. RP Kessler, BM (reprint author), Univ Oxford, Ctr Cellular & Mol Physiol, Nuffield Dept Clin Med, Roosevelt Dr, Oxford OX3 7BN, England. EM bmk@ccmp.ox.ac.uk OI Altun, Mikael/0000-0002-6937-6124; Kessler, Benedikt/0000-0002-8160-2446 FU NCI NIH HHS [1P50 CA100707]; NHLBI NIH HHS [T32 HL07574]; NIGMS NIH HHS [R01 GM62502] NR 29 TC 86 Z9 87 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2005 VL 65 IS 17 BP 7896 EP 7901 DI 10.1158/0008-5472.CAN-05-0506 PG 6 WC Oncology SC Oncology GA 961JX UT WOS:000231659500049 PM 16140960 ER PT J AU Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Flanagan, HL Whang, EE AF Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Flanagan, HL Whang, EE TI Brachial plexus injury from CT-guided RF ablation under general anesthesia SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE brachial plexus injury; general anesthesia; CT; RF ablation ID RADIOFREQUENCY ABLATION; LESIONS AB Brachial plexus injury in a patient under general anesthesia (GA) Is not uncommon, despite careful positioning and, particularly, awareness of the possibility. The mechanism of injury is stretching and compression of the brachial plexus over a prolonged period. Positioning the patient within the computed tomography (CT) gantry for abdominal or chest procedures can simulate a surgical procedure, particularly when GA is used. The potential for brachial plexus injury is increased if the case is prolonged and the patient's arms are raised above the head to avoid CT image degradation from streak artifacts. We report a case of profound brachial plexus palsy following a CT-guided radiofrequency ablation procedure under GA. Fortunately, the patient recovered completely. We emphasize the mechanism of injury and detail measures to combat this problem, such that radiologists are aware of this potentially serious complication. C1 Univ Massachusetts, Dept Radiol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shankar, S (reprint author), Univ Massachusetts, Dept Radiol, Worcester, MA 01655 USA. EM shankars@ummhc.org NR 10 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD SEP-OCT PY 2005 VL 28 IS 5 BP 646 EP 648 DI 10.1007/s00270-004-0282-3 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 966PU UT WOS:000232033900015 PM 16091989 ER PT J AU Zerbini, LF Wang, YH Correa, RG Cho, JY Libermann, TA AF Zerbini, LF Wang, YH Correa, RG Cho, JY Libermann, TA TI Blockage of NF-kappa B induces serine 15 phosphorylation of mutant p53 by JNK kinase in prostate cancer cells SO CELL CYCLE LA English DT Article DE NF-kappa B; GADD45 family; p53; serine 15; phosphorylation; JNK; apoptosis ID DNA-DAMAGE; APOPTOTIC ACTIVITY; TUMOR-SUPPRESSOR; ACTIVATES P53; GROWTH-ARREST; MUTATIONS; PROTEIN; TRANSACTIVATION; STABILIZATION; TRANSDUCTION AB The p53 tumor suppressor gene plays an important role during induction of apoptosis in cancer. In contrast, NF-kappa B prevents apoptosis in response to chemotherapeutic agents and is a critical regulator of cell survival. Despite the riches of information on the regulation of wild-type p53 function by phosphorylation, nothing is known about the modulation of mutant p53 activity by phosphorylation. Here we report that inhibition of NF-kappa B in DU145 prostate cancer cells results in p53 mutant phosphorylation at serine 15 (Ser15), leading to an increase of p53 stability, DNA binding and gain of function. Serine 15-phosphorylation is due to GADD45 alpha-dependent induction of JNK kinase, which can be blocked by SP600125, a JNK kinase inhibitor. Furthermore, inhibition of GADD45 alpha by small interfering RNA blocks JNK activation and abrogates Ser15 phosphorylation. Together, these results highlight the importance of Ser15 phosphorylation in regulating the oncogenic function of mutant p53 and apoptosis induction in the context of the NF-kappa B/I kappa B signaling pathway. C1 Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. Kyungpook Natl Univ, Sch Dent, Dept Biochem, Taegu, South Korea. RP Zerbini, LF (reprint author), Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, 4 Blackfan Circle, Boston, MA 02115 USA. EM lzerbini@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; Correa, Ricardo/G-7613-2012; Zerbini, Luiz /B-7720-2015; OI Correa, Ricardo/0000-0001-6940-7034; Libermann, Towia/0000-0002-4006-8179 FU NCI NIH HHS [1R01 CA85467, P50 CA090381, P50 CA105009] NR 49 TC 29 Z9 31 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2005 VL 4 IS 9 BP 1247 EP 1253 PG 7 WC Cell Biology SC Cell Biology GA 959JB UT WOS:000231512900025 PM 16082226 ER PT J AU Stevaux, O Dimova, DK Ji, JY Moon, NS Frolov, MV Dyson, NJ AF Stevaux, O Dimova, DK Ji, JY Moon, NS Frolov, MV Dyson, NJ TI Retinoblastoma family 2 is required in vivo for the tissue-specific repression of dE2F2 target genes SO CELL CYCLE LA English DT Article DE E2F; RB; differentiation; cell cycle; cell type specific; repression; Drosophila ID OVARIAN-FOLLICLE CELLS; DROSOPHILA-MELANOGASTER; E2F FAMILY; TRANSCRIPTION FACTOR; TUMOR-SUPPRESSOR; DNA-REPLICATION; S-PHASE; MECHANISMS; EXPRESSION; CYCLE AB In higher eukaryotes, the Retinoblastoma and E2F families of proteins control the transcription of a large number of target genes. Here, we have mutated the second Drosophila Retinoblastoma family gene (Rbf2), and contrasted the in vivo molecular functions of RBF2 with dE2F2, the only E2F partner of RBF2. Previous studies failed to uncover a unique role for RBF2 in E2F regulation. Here we find that RBF2 functions in concert with dE2F2 in vivo to repress the expression of differentiation markers in ovaries and embryos where RBF2 is highly expressed. We have compared the profiles of transcripts that are mis-expressed in ovaries, embryos and S2 cells where RBF2 function has been ablated and find that RBF2 and dE2F2 control strikingly different transcriptional programs in each situation. In vivo promoter occupancy studies point to the redistribution of dE2F/RBF complexes to different promoters in different cell types as one mechanism governing the tissue-specific regulation of dE2F/RBF target genes. These results demonstrate that RBF2 has a unique function in repressing E2F-regulated differentiation markers and that dE2F2 and RBF2 are required to regulate different sets of target genes in different tissues. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NCI NIH HHS [F32 CA93045]; NIGMS NIH HHS [GM53203]; PHS HHS [P01C95281] NR 51 TC 32 Z9 33 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2005 VL 4 IS 9 BP 1272 EP 1280 PG 9 WC Cell Biology SC Cell Biology GA 959JB UT WOS:000231512900028 PM 16082225 ER PT J AU Tarui, T Takahashi, T Nowakowski, RS Hayes, NL Bhide, PG Caviness, VS AF Tarui, T Takahashi, T Nowakowski, RS Hayes, NL Bhide, PG Caviness, VS TI Overexpression of p27(Kip1), probability of cell cycle exit, and laminar destination of neocortical neurons SO CEREBRAL CORTEX LA English DT Article DE cell cycle; cell specification; neurogenesis; p27(Kip1); tet-system ID MURINE CEREBRAL WALL; CENTRAL-NERVOUS-SYSTEM; CDK INHIBITOR; MICE LACKING; PROLIFERATIVE EPITHELIUM; NEUROEPITHELIAL CELLS; QUANTITATIVE-ANALYSIS; FATE DETERMINATION; DEPENDENT KINASES; INTRINSIC TIMER AB Neocortical projection neurons arise from a pseudostratified ventricular epithelium (PVE) from embryonic day 11 (E11) to E17 in mice. The sequence of neuron origin is systematically related to mechanisms that specify neuronal class properties including laminar fate destination. Thus, the neurons to be assembled into the deeper layers are the earliest generated, while those to be assembled into superficial layers are the later generated neurons. The sequence of neuron origin also correlates with the probability of cell cycle exit ((I) and the duration of G1-phase of the cell cycle (T-G1) in the PVE. Both Q and T-G1 increase as neuronogenesis proceeds. We test the hypothesis that mechanisms regulating specification of neuronal laminar destination, (I and T-G1 are coordinately regulated. We find that overexpression of p27(Kip1) in the PVE from E12 to E14 increases (I but not TG1 and that the increased (I is associated with a commensurate increase in the proportion of exiting cells that is directed to superficial layers. We conclude that mechanisms that govern specification of neocortical neuronal laminar destination are coordinately regulated with mechanisms that regulate (I and are independent of mechanisms regulatory to cell cycle duration. Moreover, they operate prior to postproliferative mechanisms necessary to neocortical laminar assembly. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Keio Univ, Sch Med, Tokyo, Japan. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,VBK-901, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS43246, R01 NS012005, R01 NS043426, NS12005] NR 66 TC 66 Z9 66 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2005 VL 15 IS 9 BP 1343 EP 1355 DI 10.1093/cercor/bhi017 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 956JV UT WOS:000231296900007 PM 15647527 ER PT J AU Lin, J Yang, R Tarr, PT Wu, PH Handschin, C Li, S Yang, W Pei, L Uldry, M Tontonoz, P Newgard, CB Spiegelman, BM AF Lin, J Yang, R Tarr, PT Wu, PH Handschin, C Li, S Yang, W Pei, L Uldry, M Tontonoz, P Newgard, CB Spiegelman, BM TI Hyperlipidemic effects of dietary saturated fats mediated through PGC-1 beta coactivation of SREBP SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Meeting Abstract CT 46th International Conference on the Bioscience of Lipids CY SEP 20-24, 2005 CL Ajaccio, FRANCE SP Agilent Technologies, Alexis Biochem, Avanti Polar Lipids, Caymen, Fondaz Giovanni Lorenzini Med Sci Fdn, GERLI, GlaxoSmithKline, Lesieur, Nutr Fdn Italy, Reg Corsica, Sanofi Aventis, SPI BIO, Takeda, Univ Milan, Waters C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD SEP PY 2005 VL 136 IS 2 BP 95 EP 95 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 971CN UT WOS:000232358800013 ER PT J AU Atwood, CW AF Atwood, CW TI Sleep-related hypoventilation: The evolving role of leptin SO CHEST LA English DT Editorial Material ID RESPIRATORY DEPRESSION; HUMAN OBESITY; NITRIC-OXIDE C1 Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Atwood, CW (reprint author), Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, NW628 MUH, Pittsburgh, PA 15260 USA. EM atwoodcw@upmc.edu NR 14 TC 12 Z9 12 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2005 VL 128 IS 3 BP 1079 EP 1081 DI 10.1378/chest.128.3.1079 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 964YN UT WOS:000231917000001 PM 16162684 ER PT J AU Littner, MR Leung, FW Ballard, ED Huang, BD Samra, NK AF Littner, MR Leung, FW Ballard, ED Huang, BD Samra, NK CA Lansoprazole Asthman Study Grp TI Effects of 24 weeks of lansoprazole therapy, on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms SO CHEST LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-College-of-Gastroenterology CY OCT 18-23, 2002 CL SEATTLE, WA SP Amer Coll Gastroenterol DE asthma; exacerbation; gastroesophagael acid reflux; lansoprazole; proton-pump inhibitor ID GASTROESOPHAGEAL-REFLUX; DOUBLE-BLIND; BUDESONIDE; OMEPRAZOLE; DISEASE; QUESTIONNAIRE; FORMOTEROL; REGIMEN; TRIAL; PH AB Background: Difficult-to-control asthma has been associated with gastroesophageal acid reflux. Acid-suppressive treatment has been inconsistent in improving asthma control. Objective: To determine whether a proton-pump inhibitor improves asthma control in adult asthmatic patients with acid reflux symptoms. Design: Multicenter, double-blind, randomized, placebo-controlled trial. Setting: Twenty-nine private practices and 3 academic practices in the United States. Patients: Two hundred seven patients receiving usual asthma care including an inhaled corticosteroid (ICS). Patients had acid reflux symptoms and moderate-to-severe persistent asthma. Intervention: Lansoprazole, 30 mg bid, or placebo, bid, for 24 weeks. Measurements: The primary outcome measure was daily asthma symptoms by diary,. Secondary asthma outcomes included rescue albuterol use, daily morning and evening peak expiratory flow, FEV1, FVC, asthma quality of life with standardized activities (AQLQS) questionnaire score, investigator-assessed symptoms, exacerbations, and oral corticosteroid-treated exacerbations. Results: Daily asthma symptoms, albuterol use, peak expiratory flow, FEN1, FVC, and investigator-assessed asthma symptoms at 24 weeks did not improve significantly,with lansoprazole treatment compared to placebo. The AQLQS emotional function domain improved at 24 weeks (p = 0.025) with lansoprazole therapy. Fewer patients receiving lansoprazole (8.1% vs 20.4%, respectively, p = 0.017) had exacerbations and oral corticosteroid-treated (ie, moderate-to-severe) exacerbatons (4% vs 13.9%, respectively; p = 0.016) of asthma. A post hoc subgroup analysis revealed that fewer patients receiving one or more long-term asthma-control medications in addition to an ICS experienced exacerbations (6.5% vs 24.6%, respectively; p = 0.016) and moderate-to-severe exacerbations (2.2% vs 17.5%, respectively; p = 0.021) with lansoprazole therapy. Conclusion: In adult patients with moderate-to-severe persistent asthma and symptoms of acid reflux, treatment with 30 mg of lansoprazole bid for 24 weeks did not improve asthma symptoms or pulmonary function, or reduce albuterol use. However, this dose significantly reduced asthma exacerbations and improved asthma quality of life, particularly in those patients receiving more than one asthma-control medication. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Sepulveda, CA USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Littner, MR (reprint author), Vet Adm Med Ctr, 111P, Sepulveda, CA 91343 USA. EM mlittner@ucla.edu NR 23 TC 108 Z9 115 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2005 VL 128 IS 3 BP 1128 EP 1135 DI 10.1378/chest.128.3.1128 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 964YN UT WOS:000231917000014 PM 16162697 ER PT J AU Huang, YQ White, DP Malhotra, A AF Huang, YQ White, DP Malhotra, A TI The impact of anatomic manipulations on pharyngeal collapse - Results from a computational model of the normal human upper airway SO CHEST LA English DT Article DE breathing; computational model; lung; MRI; obstructive sleep apnea; pharyngeal collapse ID OBSTRUCTIVE SLEEP-APNEA; BLOOD-PRESSURE; APNOEA/HYPOPNOEA SYNDROME; CLOSING PRESSURES; MUSCLE ACTIVATION; RESPIRATORY PUMP; PARALLEL TRIAL; CPAP THERAPY; UVULOPALATOPHARYNGOPLASTY; COLLAPSIBILITY AB Obstructive sleep apnea (OSA) is a common disease with important neurocognitive and cardiovascular sequelae. Existing therapies are unsatisfactory, leading investigators to seek alternative forms of anatomic manipulation to influence pharyngeal mechanics. We have developed a two-dimensional computational model of the normal human upper airway based on signal averaging of MRI Using the finite element method, we can perform various anatomic perturbations on the structure in order to assess the impact of these manipulations on pharyngeal mechanics and collapse. By design, the normal sleeping upper airway model collapses at - 13 cm H2O. This closing pressure becomes more negative (ie, less collapsible) when we perform mandibular advancement (- 21 cm H2O), palatal resection (- 18 cm H2O), or palatal stiffening (- 17 cm H2O). Where clinical data are available in the literature, the results of our model correspond reasonably well. Furthermore, our model provides information regarding the site of, hypotheses for clinical studies that can he undertaken in the future (eg, obstruction and provides by combination therapies). We believe that, in the future, finite element modeling will provide a useful tool to help advance our understanding of OSA and its response to various therapies. C1 Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Sleep Med Div, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Malhotra, A (reprint author), Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Sleep Med Div, 75 Francis St, Boston, MA 02115 USA. EM amalhotra1@partners.org FU NHLBI NIH HHS [HL60292, R01 HL48531, P50 HL060292, R01 HL073146-02, R01 HL073146, R01 HL048531]; NIA NIH HHS [K23 AG024837, K23 AG024837-03, AG024837-01] NR 45 TC 36 Z9 41 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2005 VL 128 IS 3 BP 1324 EP 1330 DI 10.1378/chest.128.3.1324 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 964YN UT WOS:000231917000042 PM 16162725 ER PT J AU Dhillon, SS Mahadevan, K Bandi, V Zheng, ZL Smith, W Rumbaut, RE AF Dhillon, SS Mahadevan, K Bandi, V Zheng, ZL Smith, W Rumbaut, RE TI Neutrophils, nitric oxide, and microvascular permeability in severe sepsis SO CHEST LA English DT Article DE alpha(4)-integrin; capillary permeability; neutrophils; nitric oxide; plethysmography; sepsis ID VENOUS CONGESTION PLETHYSMOGRAPHY; HUMAN SEPTIC SHOCK; CAPILLARY-PERMEABILITY; VASCULAR-PERMEABILITY; RAT MODEL; L-NAME; NITRITE/NITRATE; INHIBITION; SYNTHASE; PATHWAY AB Study objectives: Alterations in microvascular permeability are prevalent in patients with sepsis; a recent study reported that patients with septic shock had increased capillary filtration coefficient (Kf), a noninvasive index of microvascular permeability. We aimed to determine whether patients with severe sepsis had increased Kf, and whether the magnitude of Kf correlated with indexes of nitric oxide activity and neutrophil activation. Design: Single-center, prospective study. Setting: Twenty-five-bed ICU of a medical college-affiliated teaching hospital. Patients: Fifteen ICU patients with severe sepsis based on the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria of 1992, and 10 nonseptic ICU patients as control subjects. Interventions: Kf was measured by, venous congestion plethysmography, plasma nitrate/nitrite (NOx) by chemiluminescence, and neutrophil expression alpha(4)-integrin (an index of neutrophil activation) by flow cytometry. Measurements and results: Septic patients had higher Kf than nonseptic control subjects. Kr of septic patients was 5.6 +/- 0.6 X 10(-3) mL-min center dot 100 mL tissue(-1) mm Hg-1 (mean +/- SEM, mL center dot min(-1) 100 mL tissue(-1)center dot mm Hg-1 = Kf units [KfU]) as compared to 3.9 +/- 0.5 X 10(-3) KfU in nonseptic ICU patients (p < 0.05). There was no correlation between plasma NOx and Kf, or between neurophil alpha(4)-integtin expression and Kr in patients with sepsis. Septic patients with clinical evidence of edema had significantly higher Kf (p < 0.05) than nonedematous septic patients. Conclusions: ICU patients with severe sepsis have increased Kf, a noninvasive index of microvascular water permeability. The magnitude of hyperpermeability did not correlate with NOx levels or one index of neutrophil activation (alpha(4)-integrin expression). Presence of peripheral edema in these patients was associated with increased Kf, and may, represent a simple, clinical in sepsis. indicator of altered microvascular permeability in sepsis. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. VA Med Ctr, Med Care Line, Houston, TX USA. RP Rumbaut, RE (reprint author), Baylor Coll Med, Dept Med, CNRC Bldg,Room 6014,110 Bates St, Houston, TX 77030 USA. EM rrumbaut@bcm.fmc.edu OI Dhillon, Samjot/0000-0003-2955-2266 FU NHLBI NIH HHS [HL-070537] NR 33 TC 25 Z9 26 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2005 VL 128 IS 3 BP 1706 EP 1712 DI 10.1378/chest.128.3.1706 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 964YN UT WOS:000231917000095 PM 16162778 ER PT J AU Aleryani, SL Cluette-Brown, JE Khan, ZA Hasan, H de Heredia, LL Laposata, M AF Aleryani, SL Cluette-Brown, JE Khan, ZA Hasan, H de Heredia, LL Laposata, M TI Fatty acid methyl esters are detectable in the plasma and their presence correlates with liver dysfunction SO CLINICA CHIMICA ACTA LA English DT Article DE fatty acid methyl esters; liver and pancreatic dysfunction; alanine aminotransferase; aspartate aminotransferase; gas chromatography-mass spectrometry ID BLOOD METHANOL CONCENTRATIONS; ALCOHOL-ABUSE; ETHYL-ESTER; S-ADENOSYLMETHIONINE; PANCREATIC INJURY; IDENTIFICATION; PALMITATE; SYNTHASE; ETHANOL; RAT AB Background: Methanol is a component of certain alcoholic beverages and is also an endogenously formed product. On this basis, we have proposed that methanol may promote synthesis of fatty acid methyl esters (FAMEs) in the same way that ethanol promotes fatty acid ethyl ester (FAEE) synthesis. We tested the hypothesis that FAMEs appear in the blood after ethanol intake. Methods: Patient plasma samples obtained from our laboratory (n = 78) were grouped according to blood ethanol concentrations (intoxicated, blood ethanol > 800 mg/l) and non-intoxicated. These samples were further subdivided into groups based on whether the patient had normal or abnormal liver function tests (abnormal, defined as > 1 abnormality of plasma alanine and aspartate aminotransferase, albumin, total bilirubin, and alkaline phosphatase). A separate set of plasma samples were also divided into normal and abnormal groups based on pancreatic function tests (amylase and lipase). There were no patients with detectable ethanol in this group. Patients with abnormalities in pancreatic function tests were included upon recognition of endogenously produced FAMEs by patients with liver function test abnormalities. FAMEs were extracted from plasma and individual species of FAMEs quantified by gas chromatography-mass spectrometry (GUMS). Results: Increased concentrations of FAME were found in patient samples with evidence of liver dysfunction, regardless of whether or not they were intoxicated (n =21, p =0.01). No significant differences in plasma FAME concentrations were found between patients with normal (n = 15) versus abnormal pancreatic function tests (n =22, p=0.72). Conclusions: The presence of FAMEs in human plasma may be related to the existence of liver disease, and not to blood ethanol concentrations or pancreatic dysfunction. The metabolic pathways associated with FAME production in patients with impaired liver function remain to be identified. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Sanaa Univ, Sch Med & Hlth Sci, Dept Clin Biochem, Sanaa, Yemen. Northeastern Univ, Dept Biomed Sci, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Gray Bldg,Room J-235, Boston, MA 02114 USA. EM mlaposata@partners.org NR 34 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD SEP PY 2005 VL 359 IS 1-2 BP 141 EP 149 DI 10.1016/j.cccn.2005.03.038 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 959QK UT WOS:000231532800014 PM 15894299 ER PT J AU Maecker, B von Bergwelt-Baildon, MS Anderson, KS Vonderheide, RH Anderson, KC Nadler, LM Schultze, JL AF Maecker, B von Bergwelt-Baildon, MS Anderson, KS Vonderheide, RH Anderson, KC Nadler, LM Schultze, JL TI Rare naturally occurring immune responses to three epitopes from the widely expressed tumour antigens hTERT and CYP1B1 in multiple myeloma patients SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE CYP1B1; hTERT; T cell immunity; tumour antigen; immunotherapy ID T-CELL RESPONSES; TRANSFECTED DENDRITIC CELLS; CANCER-PATIENTS; LYMPHOCYTES; IDENTIFICATION; IMMUNOTHERAPY; CD8(+); INDIVIDUALS; SURVIVIN AB The widely expressed tumour antigens hTERT and CYP1B1 are commonly expressed in multiple myeloma (MM) cells. Several trials targeting these antigens by immunotherapy have been initiated. The aim of this study was to explore whether patients with MM have an endogenous pre-existing immune response against recently identified epitopes from hTERT and CYP1B1. Peripheral blood T cells from 27 HLA-A*0201(+) multiple myeloma patients at different stages of disease and 20 healthy HLA-A*0201(+) donors were enriched and studied for the presence of hTERT- and CYP1B1-specific cytotoxic T cells using MHC tetramer detection and short-term ex vivo expansion. No significant expansion of tetramer-positive cells was detected in the peripheral blood of either MM patients or healthy controls when cells were stained with tetramers containing the dominant hTERT-derived epitope or two peptides derived from CYP1B1. A single ex vivo peptide stimulation led to the detection of a small population (0.3-0.5%) of hTERT-specific cells in two of 27 patients with MM. None of the patients or controls showed significant expansion of CYP1B1-specific cells after a single peptide stimulation. Thus, endogenous in vivo priming of T cells against hTERT and CYP1B1 is a rare event in MM patients. These results suggest that strategies targeting hTERT and CYP1B1 may have to utilize techniques to induce T cell responses from a naive precursor frequency. C1 Univ Cologne, Dept Hematol & Oncol, Clin Internal Med 1, D-50924 Cologne, Germany. Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Schultze, JL (reprint author), Univ Cologne, Dept Hematol & Oncol, Clin Internal Med 1, Joseph Stelzmann Str 9, D-50924 Cologne, Germany. EM joachim.schultze@medizin.uni-koeln.de RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [K08 CA088444, K08-CA-8844401, P01 CA066996, P01 CA078378, P01-CA-66996, P01-CA-78378] NR 24 TC 25 Z9 29 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD SEP PY 2005 VL 141 IS 3 BP 558 EP 562 DI 10.1111/j.1365-2249.2005.02879.x PG 5 WC Immunology SC Immunology GA 947FH UT WOS:000230628300022 PM 16045747 ER PT J AU Bast, RC Lilja, H Urban, N Rimm, DL Fritsche, H Gray, J Veltri, R Klee, G Allen, A Kim, N Gutman, S Rubin, MA Hruszkewycz, A AF Bast, RC Lilja, H Urban, N Rimm, DL Fritsche, H Gray, J Veltri, R Klee, G Allen, A Kim, N Gutman, S Rubin, MA Hruszkewycz, A TI Translational crossroads for biomarkers SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PROSTATE-CANCER; TISSUE MICROARRAYS; QUANTITATIVE-ANALYSIS; BREAST-CANCER; ANTIGEN PSA; EXPRESSION; DISEASE AB A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (cl) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute -supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Yale Univ, Sch Med, New Haven, CT USA. Lawrence Livermore Natl Lab, Livermore, CA USA. diaDexus, San Francisco, CA USA. Johns Hopkins Univ Hosp, Baltimore, MD 21205 USA. US FDA, Rockville, MD 20857 USA. Natl Canc Inst, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. Abbott Labs, Abbott Pk, IL 60064 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bast, RC (reprint author), Univ Texas, MD Anderson Canc Ctr, Box 355,1515 Holcombe Blvd, Houston, TX 77030 USA. EM rbast@mdanderson.org RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Lilja, Hans/0000-0001-5871-7846; Rubin, Mark/0000-0002-8321-9950 NR 16 TC 54 Z9 57 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6103 EP 6108 DI 10.1158/1078-0432.CCR-04-2213 PG 6 WC Oncology SC Oncology GA 962IB UT WOS:000231723600003 PM 16144908 ER PT J AU Goessling, W Friedman, LS AF Goessling, W Friedman, LS TI Increased liver chemistry in an asymptomatic patient SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material C1 Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM 1friedman@partners.org NR 9 TC 9 Z9 9 U1 0 U2 0 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 SEP PY 2005 VL 3 IS 9 BP 852 EP 858 DI 10.1053/S1542-3565(05)00416-7 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995NA UT WOS:000234105800007 PM 16234021 ER PT J AU Fultz, SL Goulet, JL Weissman, S Rimland, D Leaf, D Gibert, C Rodriguea-Barradas, MC Justice, AC AF Fultz, SL Goulet, JL Weissman, S Rimland, D Leaf, D Gibert, C Rodriguea-Barradas, MC Justice, AC TI Differences between infectious diseases-certified physicians and general medicine-certified physicians in the level of comfort with providing primary care to patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII-PNEUMONIA; UNITED-STATES; EXPERIENCE; SPECIALTY; ASSOCIATION; MORTALITY; HIV/AIDS; PATTERNS; THERAPY AB Background. Human immunodeficiency virus (HIV)-related mortality has decreased because of highly active antiretroviral therapy. As the life expectancy of HIV-infected patients has increased, the management of comorbid disease in such patients has become a more important concern. We examined the level of comfort self-reported by experts in HIV medicine with prescribing medications to HIV-infected patients for hyperlipidemia, diabetes, hypertension, and depression. Methods. As part of a larger project (the Veterans Aging Cohort Study), physicians at infectious diseases (ID) clinics and physicians at general medical (GM) clinics were asked to complete a survey requesting information about demographic characteristics, training and certification received, and self-reported comfort with prescribing medications for patients with hyperlipidemia, diabetes, hypertension, and/or depression. Comfort was rated using a 5-point Likert scale, with scores of 4-5 classified as "comfortable." Results. Of 150 attending physicians surveyed, 51 (34%) were ID certified, 33 (22%) were GM certified but practicing at an ID clinic, and 66 were GM certified and practicing at a GM clinic. Comorbid conditions were common among HIV-infected patients treated at the ID clinics (22% of these patients had hyperlipidemia, 17% had diabetes, 40% had hypertension, and 27% had depression). However, comfort with treating these conditions was less among physicians at the ID clinic. For example, comfort treating patients with hyperlipidemia was greater for GM-certified physicians at GM clinics than for GM-certified physicians and ID-certified physicians at ID clinics (98% vs. 73% and 71%, respectively (P < .001); for trend). A similar pattern was seen for treating patients with diabetes and hypertension (P < .0001). Comfort with treating patients with depression was generally lower, particularly among physicians at ID clinics (P < .0001). Conclusions. We found that ID-certified physicians and GM-certified physicians at ID clinics reported less comfort prescribing medications for common comorbid conditions, compared with generalist physicians at GM clinics, despite a substantial prevalence of these conditions at the ID clinics. Methods are needed to increase physicians' level of comfort for prescribing treatment and/or to facilitate referral to other physicians for treatment. C1 Vet Affairs Connecticut Healthcare Syst, West Haven, CT 06516 USA. Yale Univ, Sch Med, Sect Gen Med, New Haven, CT USA. Hosp St Raphael, New Haven, CT USA. Vet Affairs Med Ctr, Atlanta, GA 30033 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Justice, AC (reprint author), Vet Affairs Connecticut Healthcare Syst, Bldg 35A,Rm 2-212 11-ACSLG,950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@med.va.gov OI Goulet, Joseph/0000-0002-0842-804X FU NIA NIH HHS [K08 AG00826]; PHS HHS [U01-13566] NR 16 TC 27 Z9 27 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2005 VL 41 IS 5 BP 738 EP 743 DI 10.1086/432621 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952HW UT WOS:000230995600023 PM 16080098 ER PT J AU Scharff, L Langan, N Rotter, N Scott-Sutherland, J Schenck, C Tayor, N McDonald-Nolan, L Masek, B AF Scharff, L Langan, N Rotter, N Scott-Sutherland, J Schenck, C Tayor, N McDonald-Nolan, L Masek, B TI Psychological, behavioral, and family characteristics of pediatric patients with chronic pain - A 1-year retrospective study and cluster analysis SO CLINICAL JOURNAL OF PAIN LA English DT Article DE pediatric chronic pain; psychological assessment; cluster analysis ID RECURRENT ABDOMINAL-PAIN; CHILD HEALTH-STATUS; FUNCTIONAL DISABILITY; COPING STRATEGIES; INVENTORY; SOMATIZATION; DEPRESSION; SYMPTOMS AB Objectives: There has been a longstanding recognition that adult patients with chronic pain are not a homogenous population and that there are subgroups of patients who report high levels of distress and inter-personal difficulties as well as subgroups of patients who report little distress and high functioning. The purpose of the present study was to attempt to identify similar subgroups in a pediatric chronic pain population. Methods: The sample consisted of 117 children with chronic pain and their parents who were assessed in a multidisciplinary pain clinic during 2001. Participants completed a set of psychologic self-report questionnaires, as well as demographic and pain characteristic information. A cluster analysis was conducted to identify 3 distinct subgroups of patients to replicate similar studies of adult chronic pain sufferers. Results: Overall, mean scores were within population norms on measures of distress and family functioning, with somatic symptoms at a level of clinical significance. The cluster analysis identified the 3 subgroups that were strikingly similar to those identified in adult chronic pain populations: one with high levels of distress and disability, another with relatively low scores on distress and disability, and a third group that scored in between the other 2 on these measures but with marked low family cohesion. Discussion: The similarity of these subgroups to the adult chronic pain population subgroups as well as implications for future studies are discussed. C1 Childrens Hosp, Pain Treatment Serv, Boston, MA 02115 USA. Yale Univ, Dept Nursing, New Haven, CT USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Scharff, L (reprint author), Childrens Hosp, Pain Treatment Serv, 300 Longwood Ave, Boston, MA 02115 USA. NR 29 TC 24 Z9 24 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD SEP-OCT PY 2005 VL 21 IS 5 BP 432 EP 438 DI 10.1097/01.ajp.0000130160.40974.f5 PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 959RA UT WOS:000231534600009 PM 16093749 ER PT J AU Mankin, HJ Hornicek, FJ Harris, M AF Mankin, HJ Hornicek, FJ Harris, M TI Total femur replacement procedures in tumor treatment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY JUL, 2004 CL Long Beach, CA SP Musculoskeletal Tumor Soc ID TERM-FOLLOW-UP; BONE ALLOGRAFTS; RESECTION; OSTEOSARCOMA; SARCOMA; SYSTEM AB Replacement of bone segments after resection of a tumor containing bone has a long history, and currently metallic implants and allografts have reasonable rates of success in terms of patient survival and restoration of useful function. Total femoral resections for extensive tumors are uncommon but clearly represent a major problem, which in the past has required hip disarticulations. In recent years, resection and replacement using custom metallic implants and more recently modular devices have allowed the patients to be restored to reasonable function. Allografts have not been used commonly for this purpose. During the past 23 years, we have done 15 total femoral replacements for osteosarcoma, chondrosarcoma, metastatic carcinoma, and an osteonecrotic fractured femur in a patient with rheumatoid arthritis and for a patient with severe deformity based on Paget's disease. Ten of these patients had allografts implanted with total hip replacement and total knee replacement implants and five patients had metallic implants. Eight of the patients died from disease, but the remaining seven have done reasonably well in terms of function and absence of complications such as fracture or infection. None of the patients required an amputation. The procedure is complex and metallic implant and allograft implantation require wide surgery and special systems of reconstruction. 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 28 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2005 IS 438 BP 60 EP 64 DI 10.1097/01.blo.0000180047.05091.fe PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 962HN UT WOS:000231721800012 ER PT J AU Mankin, HJ Hornicek, FJ AF Mankin, HJ Hornicek, FJ TI Paget's sarcoma - A historical and outcome review SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY JUL, 2004 CL Long Beach, CA SP Musculoskeletal Tumor Soc ID HIGH-GRADE OSTEOSARCOMA; OSTEOGENIC-SARCOMA; NEOADJUVANT CHEMOTHERAPY; OSTEITIS DEFORMANS; DISEASE; BONE; EXTREMITY AB Paget's sarcoma is a rare entity that principally occurs in elderly people with extensive Paget's disease. The primary sites of occurrence are the pelvis, proximal femur, proximal humerus, and calvarium. The lesions are highly malignant and the patients frequently are found to have metastases at the time of discovery. The survival rate reported in the literature generally is very poor. We were able to locate 16 patients with Paget's sarcoma in the Dr. Henry L. Jaffe Pathology Collection treated from 1942 to 1967. These were added to 27 patients treated for the disease by the Harvard Orthopaedic Oncology Group from 1972 to 2001. Three were giant cell tumors, which are occasionally found in patients with florid Paget's disease but are not malignant. Of the remaining 40 patients, outcome data were available on 35 patients. The rate of Musculoskeletal Tumor Society Stage III tumors was very high (35%) and the rate of survival was 14% at approximately 2.5 years, without differences between the two series. In view of the remarkable concordance in the poor survival figures for patients treated between 1946 and 1967 and those treated between 1972 and 2001 it appears that little progress has occurred in the treatment of Paget's sarcoma over the years, which is in sharp contrast with the current statistics for standard osteosarcoma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hmankin@partners.org NR 42 TC 33 Z9 34 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2005 IS 438 BP 97 EP 102 DI 10.1097/01.blo.0000180053.99840.27 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 962HN UT WOS:000231721800018 ER PT J AU Anderson, ME Hornicek, FJ Gebhardt, MC Raskin, KA Mankin, HJ AF Anderson, ME Hornicek, FJ Gebhardt, MC Raskin, KA Mankin, HJ TI Alveolar soft part sarcoma - A rare and enigniatic entity SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Musculoskeletal-Tumor-Society CY JUL, 2004 CL Long Beach, CA SP Musculoskeletal Tumor Soc ID TISSUE SARCOMA; ADOLESCENTS; CHILDREN; 17Q25; GENE AB Alveolar soft part sarcoma is a rare malignant tumor with unusual clinical behavior. Treatment of alveolar soft part sarcoma has been difficult to evaluate because of the small numbers of cases seen, but it seemed that although treatment of the primary tumor in alveolar soft part sarcoma often is successful, treatment of metastatic tumors is unsuccessful. A review of outcome after treatment of primary and metastatic disease in the 15 patients in our database with alveolar soft part sarcoma was done in order to evaluate this issue. Nine of 15 patients presented with metastatic disease and one further patient developed metastases. Treatment of primary tumors involved surgical excision in all but one patient and radiation in all patients. Adjuvant chemotherapy was administered to one patient with localized disease and to six patients with metastatic disease. There were no local recurrences. Treatment of metastatic tumors involved chemotherapy in seven patients, metastectomy in three patients, and radiation in two patients. All instances of the metastatic disease either recurred or progressed. Overall survival was 75 % at 5 years and 40 % at 10 years with a mean survival of 6.5 years, despite the high number of patients with metastatic disease. Current treatment results in good local control of primary tumors, but poor control of metastatic tumors. New approaches to treatment of metastatic alveolar soft part sarcoma must be investigated and applied. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Combined Orthopaed Oncol Program, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA USA. Childrens Hosp Boston, Boston, MA USA. RP Anderson, ME (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Shapiro 2, Boston, MA 02215 USA. EM manders6@bidmc.harvard.edu NR 17 TC 23 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2005 IS 438 BP 144 EP 148 DI 10.1097/01.blo.000180049.50832.4a PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 962HN UT WOS:000231721800025 ER PT J AU Muratoglu, OK Wannomae, K Christensen, S Rubash, HE Harris, WH AF Muratoglu, OK Wannomae, K Christensen, S Rubash, HE Harris, WH TI Ex vivo wear of conventional and cross-linked polyethylene acetabular liners SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL JOINT REPLACEMENT; TOTAL HIP-ARTHROPLASTY; CLINICAL-PERFORMANCE AB Explanted highly cross-linked polyethylene acetabular liners show third-body scratching. It was suggested that this surface damage could increase the wear rate of highly crosslinked polyethylene. We investigated the wear behavior of surgically explanted highly cross-linked and conventional acetabular liners using a hip simulator. Highly cross-linked explants showed no weight loss. The scratches and original machine marks of the highly cross-linked liners present at explantation remained during testing; the wear rates of these liners were 1.1 +/- 2.3 mg/million cycles, representing weight gain. In contrast, conventional liners showed wear rates of -12.9 +/- 1.4 mg/million cycles, representing weight loss. Wear was associated with rapid surface polishing and scratch elimination. After testing, the liners were melted to trigger shape memory and recover plastic deformation-induced surface changes. Highly cross-linked liners showed substantial recovery of original machining marks after melting, indicating that the scratches were a result of plastic deformation and not wear. None of the conventional polyethylenes showed any recovery after melting. The wear resistance of the highly cross-linked polyethylene studied was not compromised by surface changes that occurred during the first year of in vivo service. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1206,55 Fruit St, Boston, MA 02114 USA. EM orhun@alum.mit.edu NR 16 TC 18 Z9 18 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2005 IS 438 BP 158 EP 164 DI 10.1097/01.blo.0000164407.02998.8d PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 962HN UT WOS:000231721800027 ER PT J AU Wasielewski, RC Galat, DD Sheridan, KC Rubash, HE AF Wasielewski, RC Galat, DD Sheridan, KC Rubash, HE TI Acetabular anatomy and transacetabular screw fixation at the high hip center SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FEMORAL-HEAD ALLOGRAFTS; REVISION SURGERY; HIGH PLACEMENT; ARTHROPLASTY; COMPONENT; REPLACEMENT; BONE; RECONSTRUCTION; POSITION; CEMENT AB A quadrant system that defines the safe acetabular locations for screw placement exists for the anatomic hip center. We wanted to develop a similar system for the high hip center. The purposes of our study were to identify the anatomic structures at risk during placement of transacetabular screws in the high hip center, to identify maximum bone depth for screw purchase, and to determine if a high hip center quadrant system could be validated to guide placement of screws during acetabular arthroplasty. For this cadaver study of nine pelves, an acetabulum was reamed superiorly into the high hip center a distance equal to 1/2 of the native acetabular diameter. Screws exiting the acetabular bone by 15 mm were inserted before a computed tomography scan and a precise anatomic dissection were done. Structures at risk of penetration by screws include the external iliac vessels, the obturator nerve and vessels, the superior gluteal nerve and vessels, and the sciatic nerve. We found that a quadrant system at the high hip center can demarcate safe zones for screw placement. At the high hip center, only the peripheral 1/2 of the posterior quadrants are safe for screw placement. C1 Ohio State Univ, Columbus, OH 43210 USA. Mayo Clin, Rochester, MN USA. Grant Med Ctr, Columbus, OH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wasielewski, RC (reprint author), Univ Orthopaed Phys, 1335 Dublin Rd,Suite 110 E, Columbus, OH 43215 USA. EM wasielewskirc@universityortho.com NR 37 TC 10 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2005 IS 438 BP 171 EP 176 DI 10.1097/01.blo.0000165855.7624453 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 962HN UT WOS:000231721800029 ER PT J AU Woolf, AD Gardiner, P Whelan, J Alpert, HR Dvorkin, L AF Woolf, AD Gardiner, P Whelan, J Alpert, HR Dvorkin, L TI Views of pediatric health care providers on the use of herbs and dietary supplements in children SO CLINICAL PEDIATRICS LA English DT Article ID ALTERNATIVE MEDICINE USE; COMPLEMENTARY/ALTERNATIVE MEDICINE; UNITED-STATES; VITAMIN AB Herbs and dietary supplements (HDS) are widely used by adults for treating illnesses and/or preserving good health, and many parents use HDS for their children as well. Previous reports suggest parents will not divulge HDS use to health care providers for fear of their skepticism or disapproval. Yet the views of pediatric health care providers on HDS use in children are not well known. This study investigated the attitudes and practices of pediatric nurses and physicians regarding HDS use in children, in order to identify those characteristics associated with a high degree of confidence in initiating a dialogue on the topic of HDS with families in their practice. A written survey on attitudes and practices toward HDS was developed, piloted, revised, and then administered to a convenience sample of practitioners attending a regional postgraduate course in general pediatrics. Only 42% of 204 pediatric health care providers sampled felt confident in initiating discussions about the therapeutic use of herbs and dietary supplements with families in their practice. Confidence in discussing HDS with families correlated with both personal use of an HDS (OR 3.22; p=0.033) and length of time in practice less than 10 years (OR 8.26; p=0.007). Less than 18% felt that HDS were safe for children under 6 months of age; and only 35% felt they were safe for use in children < 24 months old. Only 7% felt that parents should be allowed to give their hospitalized child an herb or dietary supplement they had brought with them from home, although this increased to 35% if the herb or dietary supplement had been prescribed by a physician. Ninety-two percent of practitioners thought that HDS should be more closely regulated by the FDA. Only a minority of pediatric community practitioners felt confident in discussing HDS with families of children in their practice. Those who had been in practice for a shorter time and who had used HDS themselves were more likely to report confidence in initiating such discussions. The provision of more postgraduate educational opportunities to learn about herbs and dietary supplements may alleviate some practitioners ' concerns about their own competency in discussing HDS with families in their practice. C1 Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Tufts Univ, Sch Med, New England Med Ctr, Div Community Practice, Medford, MA 02155 USA. Tufts Univ, Sch Med, Dept Med, Medford, MA 02155 USA. Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. Vital Sci & Hlth, Newton, MA USA. Massachussets Coll Pharm & Allied Hlth Sci, Boston, MA USA. RP Woolf, AD (reprint author), Childrens Hosp, Div Gen Pediat, 1295 Boylston St,Suite 100, Boston, MA 02115 USA. FU NCCIH NIH HHS [AT005380-04] NR 24 TC 4 Z9 4 U1 2 U2 2 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD SEP PY 2005 VL 44 IS 7 BP 579 EP 587 DI 10.1177/000992280504400705 PG 9 WC Pediatrics SC Pediatrics GA 961UL UT WOS:000231687200005 PM 16151563 ER PT J AU Jan, YK Brienza, DM Geyer, MJ AF Jan, YK Brienza, DM Geyer, MJ TI Analysis of week-to-week variability in skin blood flow measurements using wavelet transforms SO CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING LA English DT Article DE heating; laser Doppler; spectrum analysis; vascular control; vasomotion ID LASER-DOPPLER FLOWMETRY; HEART-RATE-VARIABILITY; ARTERIAL OCCLUSIVE DISEASE; NITRIC-OXIDE; CUTANEOUS MICROCIRCULATION; MUSCLE FATIGUE; FLUX MOTION; OSCILLATIONS; VASOMOTION; PRESSURE AB The study of skin blood flow responses is confounded by temporal variability in blood flow measurements. Spectral analysis has been shown useful in isolating the effects of distinct control mechanisms on various stimuli in the microcirculatory system. However, the sensitivity of spectral analysis to temporal blood blow variability has not been reported. This study was designed to assess week-to-week variability in blood flow measurements using wavelet-based spectrum analysis. Ten healthy, young subjects (mean age +/- SD, 30.0 +/- 3.1 years) were recruited into the study. Incremental heating (35-45 degrees C, 1 degrees step min(-1)) was applied on the skin over the sacrum once per week for three consecutive weeks. Wavelet analysis was used to decompose the laser Doppler blood flow signal into frequency bands determined to be associated with endothelial nitric oxide (0.008-0.02 Hz), neurogenic (0.02-0.05 Hz), myogenic (0.05-0.15 Hz), respiratory (0.15-0.4 Hz), and cardiac (0.4-2.0 Hz) control mechanisms. The results showed that coefficients of variation for the power in each frequency band at baseline are smaller than the coefficients of variation of blood flow at baseline or at maximal blood flow ratio (P < 0.05). Myogenic and respiratory frequency bands showed the highest coefficients of variation among the five frequency bands. An increase in power in the endothelial nitric oxide frequency band and a decrease in power in the myogenic frequency band of the maximal blood flow response were reproduced in three consecutive weeks. Our study suggests that wavelet analysis is an effective method to overcome temporal variability in skin blood flow measurements. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Lymphedema & Wound Management Serv & Res, Pittsburgh, PA USA. RP Jan, YK (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Forbes Tower,Suite 5044, Pittsburgh, PA 15260 USA. EM yij2@pitt.edu RI Jan, Yih-Kuen/A-5374-2013 OI Jan, Yih-Kuen/0000-0001-7149-4034 NR 64 TC 23 Z9 23 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1475-0961 J9 CLIN PHYSIOL FUNCT I JI Clin. Physiol. Funct. Imaging PD SEP PY 2005 VL 25 IS 5 BP 253 EP 262 DI 10.1111/j.1475-097X.2005.00621.x PG 10 WC Physiology SC Physiology GA 955XI UT WOS:000231262200001 PM 16117727 ER PT J AU Otto, MW Powers, MB Fischmann, D AF Otto, MW Powers, MB Fischmann, D TI Emotional exposure in the treatment of substance use disorders: Conceptual model, evidence, and future directions SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE substance abuse; emotional avoidance; emotional acceptance; context; cognitive-behavioral therapy ID COGNITIVE-BEHAVIORAL THERAPY; ALCOHOL CUE REACTIVITY; SENSATION-SEEKING SCALE; PANIC DISORDER; ANXIETY SENSITIVITY; BENZODIAZEPINE TREATMENT; EXPERIENTIAL AVOIDANCE; ALPRAZOLAM TREATMENT; SMOKING CESSATION; CONTROLLED-TRIAL AB In this article, we review research on the nature and treatment of panic disorder, and apply these findings to a discussion of the role of internal cue exposure in the treatment of substance use disorders (SUDs). Two features of panic treatment were used as a model for interventions for SUDs: exposure to internal (interoceptive) cues rather than reliance on external (environmental) exposure alone, and use of cue exposure to try to inoculate individuals against future maladaptive patterns. Specifically, we emphasized the role of exposure to internal, largely emotional cues, as a way to enhance resilience to cues for relapse in individuals with SUDs. Hypothesized moderators and mediators of this treatment approach were discussed, as were similarities between this research agenda and an increasing focus on the role of emotional acceptance/tolerance in cognitive-behavioral treatments. (c) 2005 Elsevier Ltd. All rights reserved. C1 Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 OI Powers, Mark/0000-0001-7898-073X FU NIDA NIH HHS [R01 DA017904] NR 99 TC 28 Z9 29 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD SEP PY 2005 VL 25 IS 6 BP 824 EP 839 DI 10.1016/j.cpr.2005.05.002 PG 16 WC Psychology, Clinical SC Psychology GA 956VK UT WOS:000231327800007 PM 15967554 ER PT J AU Pollack, MH AF Pollack, MH TI Panic disorder: Broadening conceptualizations and improving treatment SO CNS SPECTRUMS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM mpollack@partners.org NR 0 TC 8 Z9 8 U1 0 U2 0 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 SEP PY 2005 VL 10 IS 9 SU 12 BP 4 EP 4 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 979OE UT WOS:000232953900001 ER PT J AU Stevens, JC Pollack, MH AF Stevens, JC Pollack, MH TI Pharmacologic treatment of panic disorder SO CNS SPECTRUMS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SOCIAL ANXIETY DISORDER; DOUBLE-BLIND; OPEN-LABEL; MULTICENTER TRIAL; COGNITIVE THERAPY; DRUG-INTERACTIONS; SINGLE-BLIND; PAROXETINE; EFFICACY AB Panic disorder, frequently complicated by agoraphobia in the clinical setting, is a relatively common disorder that is associated with significant morbid burden and dysfunction in affected individuals. PD treatment is focused on the reduction of panic attacks, avoidance behavior, and anticipatory anxiety, as well as the resolution of comorbid conditions, with the goal of normalizing, function and improving overall quality of life. Antidepressants, including the selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, as well as benzodiazepines, are commonly used as primary pharmaco therapies for the treatment of PD, with a variety of other novel interventions potentially useful as well, to optimize treatment outcome. CNS Spectr. 2005. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM mpollock@partners.org NR 75 TC 0 Z9 0 U1 1 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 SEP PY 2005 VL 10 IS 9 SU 12 BP 25 EP 31 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 979OE UT WOS:000232953900004 ER PT J AU Kozora, E Arciniegas, DB Filley, CM Ellison, MC West, SG Brown, MS Simon, JH AF Kozora, E Arciniegas, DB Filley, CM Ellison, MC West, SG Brown, MS Simon, JH TI Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus - Preliminary data SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE system lupus erythematosus; cognition; neurometabolites; magnetic resonance imaging volumetrics ID MAGNETIC-RESONANCE-SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; TRAUMATIC BRAIN INJURY; HIPPOCAMPAL VOLUME; MULTIPLE-SCLEROSIS; WHITE-MATTER; DISEASE; PREVALENCE; DEFICITS; MARKERS AB Objective: To correlate cognitive dysfunction with structural and neurometabolic brain findings in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). Background: Over 25% of non-NPSLE patients have cognitive dysfunction, but the cerebral basis of this observation is not well understood. Method: Seven patients with non-NPSLE and seven control subjects were given a series of neuropsychological tests and neuroimaging with magnetic resonance imaging and magnetic resonance spectroscopy. Analyses of cognitive function and structural and neurometabolic measures of the brain were performed. Results: Compared with controls, the non-NPSLE patients were significantly impaired on a global cognitive impairment index (CII). No significant differences between the groups were found in choline/creatine (Ch/Cr), N-acetylaspartic acid/Cr, or hippocampal volumes. Ch/Cr was highly associated with CII across the sample. Conclusions: This is the first study to correlate cognitive impairment with an increase in Ch/Cr ratio among patients with SLE. These results, although preliminary, suggest that changes in cerebral white matter may be important in determining the subtle cognitive impairment that may occur in patients with SLE, even in the absence of neuropsychiatric symptoms. C1 ABPP, CN, Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. Univ Colorado, Ctr Hlth Sci, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), ABPP, CN, Natl Jewish Med & Res Ctr, 1400 Jackson St, Denver, CO 80206 USA. EM Kozorae@njc.org RI Arciniegas, David/A-3792-2009 NR 43 TC 38 Z9 44 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD SEP PY 2005 VL 18 IS 3 BP 159 EP 162 DI 10.1097/01.wnn.0000181543.05064.4b PG 4 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 969LE UT WOS:000232234800004 PM 16175019 ER PT J AU Stanley, MA Veazey, C Hopko, D Diefenbach, G AF Stanley, Melinda A. Veazey, Connie Hopko, Derek Diefenbach, Gretchen TI Anxiety and-depression in chronic obstructive pulmonary disease: A new intervention and case report SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID QUALITY-OF-LIFE; COGNITIVE-BEHAVIORAL TREATMENT; RANDOMIZED CONTROLLED-TRIAL; ELDERLY-PATIENTS; SUBTHRESHOLD DEPRESSION; PSYCHOMETRIC EVALUATION; CLINICAL-SIGNIFICANCE; GENDER-DIFFERENCES; COPD PATIENTS; OLDER-ADULTS AB Anxiety and depression coexist frequently in chronic obstructive pulmonary disease and compound the impact of the disease on quality of life and functional status. However, little attention has been given to the development of treatment strategies for this subset of patients. The current article describes the development of a new, multicomponent cognitive behavioral treatment for reducing anxiety and depression among patients with respiratory disease (CBT-RADAR). Outcome data from a group of 5 patients who participated in an ongoing clinical trial are reviewed to illustrate the strengths and limitations of this intervention. C1 Baylor Coll Med, Dept Psychiat & Behav Sci, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Univ Tennessee, Knoxville, TN USA. Baylor Coll Med, Inst Living, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Stanley, MA (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM mstanley@bcm.tmc.edu NR 83 TC 16 Z9 16 U1 2 U2 6 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FAL PY 2005 VL 12 IS 4 BP 424 EP 436 DI 10.1016/S1077-7229(05)80070-7 PG 13 WC Psychology, Clinical SC Psychology GA 090SR UT WOS:000240972200007 ER PT J AU Rizvi, SL Linehan, MM AF Rizvi, Shireen L. Linehan, Marsha M. TI The treatment of maladaptive shame in borderline personality disorder: A pilot study of "opposite action" SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID NEGATIVE AFFECT; GUILT; PANAS; ANGER AB This study sought to pilot test a short-term intervention for maladaptive shame in borderline personality disorder (BPD) based on the skill of "opposite action "from dialectical behavior therapy. Five women with BPD were treated with the intervention using a single-subject, multiple-baseline design. Results indicate that, although state ratings of shame are highly variable, it is possible to reduce shame about a specific event over a short period of time. This was verified by a new shame measure that was created for this study. Results from this study have several implications for the treatment of shame in BPD and other clinical populations. A detailed case example is provided. C1 Univ Washington, Seattle, WA 98195 USA. RP Rizvi, SL (reprint author), Natl Ctr PTSD, 150 So Huntington Ave 116B, Boston, MA 02130 USA. EM shireen.rizvi@med.va.gov NR 27 TC 32 Z9 32 U1 0 U2 4 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FAL PY 2005 VL 12 IS 4 BP 437 EP 447 DI 10.1016/S1077-7229(05)80071-9 PG 11 WC Psychology, Clinical SC Psychology GA 090SR UT WOS:000240972200008 ER PT J AU Maguen, S Shipherd, JC Harris, HN AF Maguen, Shira Shipherd, Jillian C. Harris, Holly N. TI Providing culturally sensitive care for transgender patients SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article; Proceedings Paper CT 34th Annual Convention of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 2000 CL NEW ORLEANS, LA SP Assoc Advancement Behav Therapy ID POSTTRAUMATIC-STRESS-DISORDER; GENDER IDENTITY DISORDER; MALE VIETNAM VETERANS; SOCIAL SUPPORT; FEMALE; HEALTH; BEHAVIORS; NETWORKS; VIOLENCE; SAMPLE AB Culturally sensitive information is crucial for providing appropriate care to any minority population. This article provides an overview of important issues to consider when working with transgender patients, including clarification of transgender terminology, diagnosis issues, identity development, and appropriate pronoun use. We also review common clinical issues for transgender individuals seeking mental health care, how these can be addressed within a CBT framework, and the process of setting up a CBT support group within a VA hospital system. CBT group, outcome data and demonstrative examples from male to female transsexuals are also presented. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program 116P, 4150 Clement St,Bldg 8,Room 206, San Francisco, CA 94121 USA. EM shira.maguen@va.gov NR 52 TC 15 Z9 15 U1 2 U2 9 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FAL PY 2005 VL 12 IS 4 BP 479 EP 490 DI 10.1016/S1077-7229(05)80075-6 PG 12 WC Psychology, Clinical SC Psychology GA 090SR UT WOS:000240972200012 ER PT J AU Graham, DP Kunik, ME Doody, R Snow, AL AF Graham, DP Kunik, ME Doody, R Snow, AL TI Self-reported awareness of performance in dementia SO COGNITIVE BRAIN RESEARCH LA English DT Article DE Alzheimer disease; awareness; psychometrics ID STAGE ALZHEIMERS-DISEASE; IMPAIRED AWARENESS; MEMORY IMPAIRMENT; COGNITIVE DEFICITS; CAREGIVER BURDEN; ASSESSMENT SCALE; ANOSOGNOSIA; DEPRESSION; INSIGHT; UNAWARENESS AB The purpose of this study was to test the theory that patients with dementia do not update their self-perceptions based on actual performance. This experiment compared differences between post-task perceptions of performance and actual performance in persons with dementia and normal controls on seven cognitive tasks. Participants included 35 volunteers (12 with dementia and 23 without) from the Houston Veterans Affairs nursing home and geropsychiatric inpatient unit and outpatient clinics and from the Baylor College of Medicine's Alzheimer's Disease Center. Measurements included 7 subtests of the Alzheimer Disease Assessment Scale-Cognitive Subscale and standardized interview questions assessing perceived performance on each of these subtests. Participants with dementia had similar perceptions of performance to normal controls yet evidenced much worse performance on all seven cognitive screening tasks. Thirty-one percent of normal controls over-estimated their performance, compared to 64% of those with mild-moderate dementia and 93% with moderate-severe dementia. Our study supports the theory that demented individuals do not update their self-perceptions of performance. However, a large portion of normal controls was also inaccurate evaluating their own performances. Thus, post-diction measures provide useful insight into the mechanisms of self-awareness but may not be appropriate assessment tools to identify clinically significant impaired self-awareness. (c) 2005 Elsevier B.V. All rights reserved. C1 Michael E DeBakey Vet Affairs Med Ctr, HSR&D 152, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, MHCL 116, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Mental Hlth Serv Lines, Houston, TX 77030 USA. RP Graham, DP (reprint author), Michael E DeBakey Vet Affairs Med Ctr, HSR&D 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM david.graham@med.va.gov NR 57 TC 29 Z9 29 U1 0 U2 1 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 SEP PY 2005 VL 25 IS 1 BP 144 EP 152 DI 10.1016/j.cogbrainres.2005.05.001 PG 9 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 976CE UT WOS:000232709600013 ER PT J AU Krishnan, A Xu, YS Gandour, J Cariani, P AF Krishnan, A Xu, YS Gandour, J Cariani, P TI Encoding of pitch in the human brainstem is sensitive to language experience SO COGNITIVE BRAIN RESEARCH LA English DT Article DE auditory; brainstem; speech; frequency following response; experience-dependent plasticity; Mandarin Chinese tone ID FREQUENCY-FOLLOWING RESPONSES; LINGUISTIC EXPERIENCE; INFERIOR COLLICULUS; DISCHARGE PATTERNS; AUDITORY-CORTEX; COMPLEX TONES; REPRESENTATION; SPEECH; ENHANCEMENT; PLASTICITY AB Neural processes underlying pitch perception at the level of the cerebral cortex are influenced by language experience. We investigated whether early, pre-attentive stages of pitch processing at the level of the human brainstem may also be influenced by language experience. The human frequency following response (FFR), reflecting sustained phase-locked activity in a population of neural elements, was used to measure activity within the rostral brainstem. FFRs elicited by four Mandarin tones were recorded from native speakers of Mandarin Chinese and English. Pitch strength (reflecting robustness of neural phase-locking at the pitch periods) and accuracy of pitch tracking were extracted from the FFRs using autocorrelation algorithms. These measures revealed that the Chinese group exhibits stronger pitch representation and smoother pitch tracking than the English group. Consistent with the pitch data, FFR spectral data showed that the Chinese group exhibits stronger representation of the second harmonic relative to the English group across all four tones. These results cannot be explained by a temporal pitch encoding scheme which simply extracts the dominant interspike interval. Rather, these results support the possibility of neural plasticity at the brainstem level that is induced by language experience that may be enhancing or priming linguistically relevant features of the speech input. (c) 2005 Elsevier B.V. All rights reserved. C1 Purdue Univ, Dept Speech Language & Hearing Sci, W Lafayette, IN 47907 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Gandour, J (reprint author), Purdue Univ, Dept Speech Language & Hearing Sci, Heavilon Hall 1353,500 Oval Dr, W Lafayette, IN 47907 USA. EM gandour@purdue.edu NR 41 TC 190 Z9 198 U1 0 U2 14 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 SEP PY 2005 VL 25 IS 1 BP 161 EP 168 DI 10.1016/j.cogbrainres.2005.05.004 PG 8 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 976CE UT WOS:000232709600015 ER PT J AU Warren, MP Miller, KK Olson, WH Grinspoon, SK Friedman, A AF Warren, MP Miller, KK Olson, WH Grinspoon, SK Friedman, A TI Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study SO CONTRACEPTION LA English DT Article DE norgestimate; ethinyl estradiol; oral contraception; bone mineral density; metabolism; hypothalamic amenorrhea; bone markers; osteopenia ID ANOREXIA-NERVOSA; YOUNG-WOMEN; BALLET DANCERS; EXERCISE; THERAPY AB Objective: The effects of long-term triphasic oral contraceptive administration on bone mineral density (BMD) were investigated in premenopausal women with hypothalamic amenorrhea (HA) and osteopenia. Methods: After completing three 28-day cycles in the double-blind phase of a placebo-controlled trial, women (mean age, 26.7 years) who received norgestimate 180-250 mu g/ethinyl estradiol 35 mu g (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to receive open-label NGM/EE for 10 additional cycles. Results: For subjects completing 10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BNID (L1-L4) increased from 0.881 +/- 0.0624 g/cm(2) at baseline (last visit prior to NGM/EE) to 0.894 +/- 0.0654 g/cm(2) at final visit (p=.043); no significant changes in hip BNID occurred. Decreases in N-telopeptide, osteocalcin, procollagen type I propeptide and bone-specific alkaline phosphatase levels indicated effects on bone metabolism. Conclusions: Long-term administration of triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD. (c) 2005 Elsevier Inc. All rights reserved. C1 Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ortho McNeil Pharmaceut Inc, Raritan, NJ USA. Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. RP Warren, MP (reprint author), Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, 630 W 168th St, New York, NY 10032 USA. EM mpw1@columbia.edu NR 25 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD SEP PY 2005 VL 72 IS 3 BP 206 EP 211 DI 10.1016/j.contraception.2005.03.007 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 961IC UT WOS:000231654300010 PM 16102557 ER PT J AU Li, LF Liao, SK Lee, CH Tsai, YH Huang, CC Quinn, DA AF Li, LF Liao, SK Lee, CH Tsai, YH Huang, CC Quinn, DA TI Ventilation-induced neutrophil infiltration and apoptosis depend on apoptosis signal-regulated kinase 1 pathway SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; chemokine; mitogen-activated protein kinase; ventilator-induced lung injury; lung stretch; antioxidants ID INDUCED LUNG INJURY; N-TERMINAL KINASE; RESPIRATORY-DISTRESS-SYNDROME; EPITHELIAL-CELL APOPTOSIS; VASCULAR ENDOTHELIAL-CELLS; MECHANICAL VENTILATION; CONTROLLED-TRIAL; KAPPA-B; THIOREDOXIN; EXPRESSION AB objective: Positive pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including macrophage inflammatory protein (MIP)-2, a functional equivalent of human interleukin-8, neutrophil infiltration, and apoptosis. The mechanisms regulating ventilation-induced cytokine production and lung cell death are unclear. Based on our previous in vitro and in vivo models of lung cell stretch, we hypothesized that high tidal volume ventilation-induced MIP-2 production, neutrophil infiltration, and apoptosis are dependent on the activation of apoptosis signal-regulated kinase 1 (ASK1), the upstream activator of c-Jun N-terminal kinase (JNK). Design: Prospective, controlled animal experiment. Setting: University research laboratory. Subjects: Male C57BL/6 mice, weighting 20-25 g. Interventions: C57BL/6 mice were exposed to high tidal volume (30 mL/kg) or low tidal volume (6 mL/kg) mechanical ventilation for 15 mins to 5 hrs. Measurements and Main Results: High tidal volume ventilation induced MIP-2 messenger RNA expression, MIP-2 protein production, neutrophil migration into the lung, airway epithelial cell apaptosis, and activation of ASK1, JNK, and activator protein (AP)-1 DNA binding in a dose-dependent and time-dependent manner. ASK1 inhibition with thioredoxin attenuated high tidal volume ventilation-induced MIP-2 messenger RNA expression, MIP-2 protein production, neutrophil migration into the lung, airway epithelial cell apoptosis, activation of JNK, and AP-1 DNA binding. Conclusions: Our data showed that high tidal volume ventilation-induced MIP-2 production, neutrophil sequestration, and apoptotic cell death were dependent, in part, on activation of the ASK1/JNKIAP-1 pathway. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Chang Gung Mem Hosp, Grad Inst Clin Med Sci, Taoyuan, Taiwan. Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Taoyuan, Taiwan. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Quinn, DA (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM dquinn1@partners.org FU NHLBI NIH HHS [HL039020, HL61688, HL67371] NR 45 TC 20 Z9 23 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 SEP PY 2005 VL 33 IS 9 BP 1913 EP 1921 DI 10.1097/01.CCM.0000178179.48050.BC PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 042CG UT WOS:000237504200003 PM 16148459 ER PT J AU Schettino, G Altobelli, N Kacmarek, RM AF Schettino, G Altobelli, N Kacmarek, RM TI Noninvasive positive pressure ventilation reverses acute respiratory failure in select "do-not-intubate" patients SO CRITICAL CARE MEDICINE LA English DT Article DE noninvasive positive pressure ventilation; do not intubate; end-of-life; chronic obstructive pulmonary disease; cardiogenic pulmonary edema; hypoxemic respiratory failure; cancer ID OBSTRUCTIVE PULMONARY-DISEASE; REFUSED ENDOTRACHEAL INTUBATION; RANDOMIZED CONTROLLED-TRIAL; MECHANICAL VENTILATION; FACE MASK; ACUTE EXACERBATIONS; MULTICENTER; ORDERS; CARE; COMMITTEE AB Objective: To determine the outcome from the use of noninvasive positive pressure ventilation (NPPV) in "do-not-intubate" (DNI) patients in acute respiratory failure. Design: Prospective observational study. Setting: University-affiliated large medical center. Patients: All patients with DNI status who received NPPV for a 1-yr period. Interventions: None. Measurements and Main Results. Demographic, physiologic, and laboratory data were collected before initiation, 2 hrs after initiation, and each morning and evening for as long as NPPV was provided. Data were recorded on 137 episodes of acute respiratory failure in 131 DNI patients. Hospital mortality rate was 37.5% in 24 patients with an exacerbation of chronic obstructive pulmonary disease (COPD), 39% in 28 patients with acute cardiogenic pulmonary edema, 68% in nine patients with non-COPD hypercapnic ventilatory failure, 77% in 13 postextubation respiratory failure patients, and 86% in 57 patients with hypoxemic respiratory failure. Advanced cancer was present in 40 patients and was associated with increased risk of death (85% mortality rate, p = .002). A score based on the Simplified Acute Physiology Score (SAPS) II and serum albumin level calculated before NPPV was predictive of hospital outcome. Conclusions. NPPV is successful in reversing acute respiratory failure and preventing hospital mortality in DNI patients with COPD and cardiogenic pulmonary edema but not in patients with postextubation failure, hypoxemic respiratory failure, or endstage cancer. An easy-to-calculate score combining SAPS II and serum albumin level is a good prediction of outcome in DNI patients receiving NPPV. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Schettino, G (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 30 TC 76 Z9 80 U1 1 U2 2 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 SEP PY 2005 VL 33 IS 9 BP 1976 EP 1982 DI 10.1097/01.CCM.0000178176.51024.82 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 042CG UT WOS:000237504200011 PM 16148468 ER PT J AU Kobayakawa, S Jett, BD Gilmore, MS AF Kobayakawa, S Jett, BD Gilmore, MS TI Biofilm formation by Enterococcus faecalis on intraocular lens material SO CURRENT EYE RESEARCH LA English DT Article DE biofilm; E. faecalis; intraocular lens (IOL) material ID SCANNING-ELECTRON-MICROSCOPY; IN-VITRO ADHERENCE; STAPHYLOCOCCUS-EPIDERMIDIS; SURFACE PROTEIN; ENDOPHTHALMITIS VITRECTOMY; BACTERIAL ADHESION; ESP; IMPLANTATION; BACTEREMIA; OUTCOMES AB Purpose: To compare biofilm formation by Enterococcus faecalis on different intraocular lens (IOL) materials. Methods: E.faecalis biofilms were cultivated on disks of IOL material (silicone, PMMA [polymethylmethacrylate], or acrylic). Biofilms were stained with crystal violet (CV), which served as an index of biofilm formation. The bacterial population was enumerated after biofilm homogenization. Biofilms were also examined by confocal microscopy. Results: At 24 hr, there was no significant difference in biofilm formation, or the population within biofilms, among the three materials tested. However, after 48 and 72 hr, it was observed that silicone supported the least amount of biofilm formation (p < 0.05); biomass on PMMA and acrylic IOLs continued to increase, with acrylic demonstrating the greatest amount of stainable biofilm (p < 0.0005). The population on PMMA was significantly greater than the other IOL materials (p < 0.005). Confocal microscopy confirmed the lack of biomass on silicone. Conclusions: Among three IOL materials, E.faecalis biofilms formed more readily on PMMA and acrylic compared to silicone. C1 Harvard Univ, Sch Med, Microbiol Lab, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Oklahoma Baptist Univ, Shawnee, OK USA. RP Gilmore, MS (reprint author), Harvard Univ, Sch Med, Microbiol Lab, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM mgilmore@vision.eri.harvard.edu FU NEI NIH HHS [EY08289]; NIDCR NIH HHS [DE13244] NR 34 TC 14 Z9 15 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 2005 VL 30 IS 9 BP 741 EP 745 DI 10.1080/02713680591005959 PG 5 WC Ophthalmology SC Ophthalmology GA 965VB UT WOS:000231977400003 PM 16146919 ER PT J AU Kwon, RS Brugge, WR AF Kwon, RS Brugge, WR TI New advances in pancreatic imaging SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE computed tomography scan; endoscopic ultrasound; magnetic resonance imaging scan; pancreatic cancer; pancreatic cystic neoplasm ID PAPILLARY MUCINOUS TUMORS; COMPUTED-TOMOGRAPHY; ENDOSCOPIC ULTRASONOGRAPHY; AUTOIMMUNE PANCREATITIS; ENHANCED SONOGRAPHY; VASCULAR INVASION; CYSTIC NEOPLASMS; HELICAL CT; DIAGNOSIS; CANCER AB Purpose of review Exciting new developments and,applications of imaging techniques in pancreatic diseases have emerged. This review discusses these new advances and how they are improving our ability to diagnose malignancies and inflammatory lesions, to grade severity of pancreatitis, and to stage pancreatic cancer accurately. Recent findings A new computed tomography severity index shows promise for grading the severity of acute pancreatitis. Magnetic resonance imaging is comparable with computed tomography in staging acute pancreatitis. Analysis of pancreatograms and textural changes of the parenchyma may prove helpful in diagnosing chronic pancreatitis. Contrast enhanced ultrasonography may prove to be a useful way to judge the degree of inflammation and fibrosis in autoimmune pancreatitis and to monitor response to steroid therapy. The debate over the best means of staging pancreatic cancer has focused on endoscopic ultrasound and computed tomography. Preliminary studies with contrast enhanced ultrasonography report improved diagnostic and staging capabilities with pancreatic cystic and solid neoplasms. Improvements in positron emission tomography/computed tomography scans may improve the,detection of neuroendocrine tumors. Summary These new advances will help refine the diagnosis and staging of pancreatic diseases. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. EM Wbrugge@partners.org NR 43 TC 6 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2005 VL 21 IS 5 BP 561 EP 567 DI 10.1097/01.mog.0000174223.74783.1b PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 961JV UT WOS:000231659300005 PM 16093770 ER PT J AU Evans, JA Nishioka, NS AF Evans, JA Nishioka, NS TI Endoscopic confocal microscopy SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE confocal microscopy; endoscopy; optical biopsy ID IN-VIVO; BARRETTS-ESOPHAGUS; IMAGING FOCI; DYSPLASIA; DIAGNOSIS; CANCER; COLON AB Purpose of review Endoscopic confocal microscopy is a new endoscopic imaging technology that produces high-magnification cross-sectional, images of the gastrointestinal epithelium during endoscopy. These high-magnification images,,might allow the endoscopist to make a tissue diagnosis during endoscopy without biopsy and histopathology. The purpose of this article is to review the salient features of endoscopic confocal microscopy, describe current clinical research areas using the technology, and depict its potential role in the management of gastrointestinal diseases. This review includes an overview of the technology, a review of recent publications describing its function, and a discussion of potential applications. Recent findings Endoscopic confocal microscopy has been technologically feasible only for a short time; therefore, the published experience is limited. Studies describing the use of endoscopic confocal microscopy for the detection of dysplastic tissue have been limited to a single paper in which endoscopic confocal microscopy was reported to be highly sensitive and specific for the detection of colonic dysplasia in a general screening population. Active areas of investigation include detecting dysplasia in ulcerative colitis and Barrett's esophagus. A recent case report detailed the ability of endoscopic confocal microscopy to detect gastric Helicobacter pylori in vivo. Summary Endoscopic confocal microscopy is a new imaging technology that produces high-magnification cross-sectional images of the gastrointestinal tract. Its role in detecting and managing diseases of the gastrointestinal tract has been studied in colon cancer screening and is currently being evaluated in a variety of premalignant conditions. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Nishioka, NS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM nnishioka@partners.org NR 17 TC 25 Z9 25 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2005 VL 21 IS 5 BP 578 EP 584 DI 10.1097/01.mog.0000174217.62214.10 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 961JV UT WOS:000231659300008 PM 16093773 ER PT J AU Mount, DB AF Mount, DB TI Molecular physiology and the four-component model of renal urate transport SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Editorial Material ID SERUM URIC-ACID; CARDIOVASCULAR-DISEASE; MICROVILLUS MEMBRANES; INSULIN-RESISTANCE; ANION-EXCHANGER; PYRAZINAMIDE; EXCRETION; GENE; HYPERURICEMIA; COTRANSPORTER C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Gen Internal Med, Boston, MA USA. RP Mount, DB (reprint author), Vet Adm Med Ctr W Roxbury, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM dmount@rics.bwh.harvard.edu NR 30 TC 11 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2005 VL 14 IS 5 BP 460 EP 463 DI 10.1097/01.mnh.0000170749.10785.04 PG 4 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 958KA UT WOS:000231442400007 PM 16046905 ER PT J AU Ezzelarab, M Yamada, K Cooper, DKC Sachs, DH AF Ezzelarab, M Yamada, K Cooper, DKC Sachs, DH TI Pig-to-nonhuman primate organ xenotransplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE alpha 1; 3-galactosyltransferase gene-knockout; nonhuman primate; pig; thymus xenotransplantation; tolerance; xenoreactive antibodies ID PORCINE LYMPHOTROPIC HERPESVIRUS; THYMIC LOBE TRANSPLANTATION; HUMORAL XENOGRAFT REJECTION; DECAY-ACCELERATING FACTOR; MINIATURE SWINE; TRANSGENIC PIG; HEART-TRANSPLANTATION; CARDIAC XENOTRANSPLANTATION; BABOON XENOTRANSPLANTATION; COMPOSITE THYMOKIDNEYS AB Purpose of review The availability of alpha 1,3-galactosyltransferase gene-knockout pigs in which the major target for primate anti-Pig antibodies has been deleted is considered a major step toward clinical xenotransplantation. A review of progress in pig-to-nonhuman primate transplantation is therefore. timely. Recent findings Several groups have continued their studies using pigs transgenic for one or more human complement regulatory proteins, with graft survival reaching more than 3 months in some cases. Significant complications have resulted from the intensity of immunosuppression required to achieve these results, however. The use of organs from alpha 1,3-galactosyltransferase gene-knockout pigs has eliminated hyperacute rejection in baboons. Heterotopic heart alpha 1,3-galactosyltransferase gene-knockout xenografts maintained with chronic immunosuppression survived up to 6 months, with graft failure associated with thrombotic microangiopathy. Life-supporting renal xenografts maintained with a tolerance-inducing regimen survived over 80 days, with the longest survivors dying with functioning grafts. Summary The availability of alpha 1,3-galactosyltransferase gene-knockout donor pigs has eliminated the need for-inhibition of antibodies to alpha 1,3 galactose (Gal) or complement to prevent hyperacute rejection. It has also had a positive impact on the survival of heterotopic xenogeneic hearts transplanted under chronic immunosuppression and on the survival of orthotopic kidneys trans planted with donor thymus tissue in an attempt to induce tolerance. Problems remain to be resolved, including the effects of the variable presence of antibodies to non-Gal antigens, the high incidence of thrombotic microangiopathy in heart xenotransplants, and loss of animals to other causes in the recipients of orthotopic renal transplants. Nevertheless, the results with alpha 1,3-galactosyltransferase gene-knockout donors are encouraging for the future of this field. C1 Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Bldg 149,13th St, Boston, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu OI Ezzelarab, Mohamed/0000-0002-3919-5250 NR 38 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD SEP PY 2005 VL 10 IS 3 BP 234 EP 239 DI 10.1097/01.mot.0000171198.14482.dd PG 6 WC Transplantation SC Transplantation GA 968YK UT WOS:000232199300012 ER PT J AU Bardwell, PD Ohdan, H Sykes, M AF Bardwell, PD Ohdan, H Sykes, M TI B cell tolerance and xenotransplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE alpha Gal; B cells; mixed chimerism; tolerance; xenotransplantation ID MIXED XENOGENEIC CHIMERAS; ANTIBODY-PRODUCING CELLS; HEART-TRANSPLANTATION; MARGINAL ZONE; T-CELL; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; CARBOHYDRATE ANTIGEN; XENOGRAFT SURVIVAL; CD4 RECONSTITUTION; IMMUNE-RESPONSE AB Purpose of review Preformed and induced antibodies pose a major barrier to xenotransplantation. Recent experience involving allotransplantation in the presence of preformed anti-blood group antibodies and induced anti-human leukocyte antigen antibodies provides information that is -relevant to tolerance induction in xenotransplantation. This review summarizes recent advances in our understanding of 6 cell tolerance in rodent models and patients. Recent findings In the setting of pediatric heart and liver transplantation, evidence has been obtained for tolerization of anti-blood group antigen natural antibody-producing cells. In animal models, tolerance of preexisting xenoantibody-secreting cells by solid organ transplantation with immunosuppression or through the establishment of mixed chimerism has been achieved. Advances in our basic understanding of B cell tolerance mechanisms and those applying to the various transplant settings are also described. Summary B cell tolerance is a critical goal in xenotransplantation. Strategies for tolerance induction developed in the animal models may be applied clinically as an understanding of their mechanisms emerges. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. Hiroshima Univ, Grad Sch Biomed Sci, Programs Biomed Res, Dept Surg,Div Frontier Med Sci, Hiroshima, Japan. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102 13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu RI Bardwell, Philip/H-2219-2014 OI Bardwell, Philip/0000-0002-3835-255X NR 70 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD SEP PY 2005 VL 10 IS 3 BP 252 EP 258 DI 10.1097/01.mot.0000175544.97974.92 PG 7 WC Transplantation SC Transplantation GA 968YK UT WOS:000232199300015 ER PT J AU Wen, PH De Gasperi, R Sosa, MAG Rocher, AB Friedrich, VL Hof, PR Elder, GA AF Wen, PH De Gasperi, R Sosa, MAG Rocher, AB Friedrich, VL Hof, PR Elder, GA TI Selective expression of presenilin 1 in neural progenitor cells rescues the cerebral hemorrhages and cortical lamination defects in presenilin 1-null mutant mice SO DEVELOPMENT LA English DT Article DE cortical development; CNS hemorrhages; familial Alzheimer's disease; neural progenitor cells; presenilin 1 (PS1, Psen1); transgenic mice; vascular development ID CENTRAL-NERVOUS-SYSTEM; CAJAL-RETZIUS NEURONS; GFP TRANSGENIC MICE; CNS STEM-CELLS; ALZHEIMER-DISEASE; ADULT MICE; NESTIN; MOUSE; NEUROGENESIS; HIPPOCAMPUS AB Mice with a null mutation of the presenilin 1 gene (Pseu1(-/-)) die during late intrauterine life or shortly after birth and exhibit multiple CNS and non-CNS abnormalities, including cerebral hemorrhages and altered cortical development. The cellular and molecular basis for the developmental effects of Psen1 remain incompletely understood. Psen1 is expressed in neural progenitors in developing brain, as well as in postmitotic neurons. We crossed transgenic mice with either neuron-specific or neural progenitor-specific expression of Psen1 onto the Psen1(-/-) background. We show that neither neuron-specific nor neural progenitor-specific expression of Psen1 can rescue the embryonic lethality of the Psen1(-/-) embryo. Indeed neuron-specific expression rescued none of the abnormalities in Psen1(-/-) mice. However, Psen1 expression in neural progenitors rescued the cortical lamination defects, as well as the cerebral hemorrhages, and restored a normal vascular pattern in Psen1(-/-) embryos. Collectively, these studies demonstrate that Psen1 expression in neural progenitor cells is crucial for cortical development and reveal a novel role for neuroectodermal expression of Psen1 in development of the brain vasculature. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. RP Elder, GA (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM gregory.elder@mssm.edu FU NIA NIH HHS [AG23599, P01 AG002219, R01 AG020139, AG20139, R03 AG021305, AG05138, R21 AG023599, P50 AG005138, AG21305, AG02219]; NIMH NIH HHS [R01 MH064673, MH70603, R03 MH070603] NR 50 TC 18 Z9 19 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 2005 VL 132 IS 17 BP 3873 EP 3883 DI 10.1242/dev.01946 PG 11 WC Developmental Biology SC Developmental Biology GA 972CG UT WOS:000232430900008 PM 16079160 ER PT J AU Putnam, KM Silk, KR AF Putnam, KM Silk, KR TI Emotion dysregulation and the development of borderline personality disorder SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; CHILDHOOD SEXUAL-ABUSE; THREAT-RELATED STIMULI; HIPPOCAMPAL VOLUME; IMPULSIVE AGGRESSION; PREFRONTAL CORTEX; MAJOR DEPRESSION; OBJECT REPRESENTATIONS AB We review the role of emotion regulation in borderline personality disorder (BPD). We briefly discuss the historical development of BPD as a disorder where emotional regulation plays a key role. We review the concept of emotion regulation in general and explore both one-factor and two-factor models of emotion regulation. We discuss cognitive and attentional aspects of emotion regulation, and explore these regulatory controls as operating as both voluntary as well as automatic processes. We then turn to other neurophysiological models of emotion regulation in general and examine how those models, both neurophysiologically and neuroanatomically, are expressed in individuals with BPD. We examine how neuroimaging, both anatomical and functional, reveals the roles that various neuroanatomical structures play in the regulation of emotion in BPD. We conclude by creating a neurodevelopmental model that describes how a complex matrix involving the interplay of constitutional/biological predispositions with environmental stressors as well as with parental effectiveness in response to the child's emotion expression can impact key aspects of adult cognitive, affective, interpersonal, and behavioral functioning that culminate in a diagnosis of BPD. C1 Univ Michigan, Ann Arbor, MI 48109 USA. Natl Ctr PTSD, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. RP Silk, KR (reprint author), Univ Michigan, 1500 E Med Ctr,MCHC-6,Box 0295, Ann Arbor, MI 48109 USA. EM ksilk@umich.edu NR 159 TC 70 Z9 72 U1 11 U2 40 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 EI 1469-2198 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 2005 VL 17 IS 4 BP 899 EP 925 DI 10.1017/S0954579405050431 PG 27 WC Psychology, Developmental SC Psychology GA 000ZE UT WOS:000234500700002 PM 16613424 ER PT J AU Gamer, LW Nove, J Levin, M Rosen, V AF Gamer, LW Nove, J Levin, M Rosen, V TI BMP-3 is a novel inhibitor of both activin and BMP-4 signaling in Xenopus embryos SO DEVELOPMENTAL BIOLOGY LA English DT Article DE BMP-3; activin; BMP; ActRIIB; antagonist; Xenopus ID BONE MORPHOGENETIC PROTEINS; TGF-BETA SUPERFAMILY; MESODERM INDUCTION; NEURAL INDUCTION; EXPRESSION PATTERNS; SPEMANNS ORGANIZER; SPECIFICATION; GROWTH; NOGGIN; DIFFERENTIATION AB In Xenopus, the biological effects of BMP-3 oppose those of ventralizing BMPs, but the mechanism for this antagonism remains unclear. Here, we demonstrate that BMP-3 is a dorso-anteriorizing factor in Xenopus embryos that interferes with both activin and BMP signaling. BMP-3 acts by binding to ActRIIB, the common type II receptor for these proteins. Once BMP-3 binds to ActRIIB, it cannot be competed off by excess ligand making a receptor complex that is unable to activate R-Smads and transduce signal. Consistent with a model where BMP-3 interferes with activin and BMPs through a shared receptor, we show that overexpression of BMP-3 can only be rescued by co-injection of xActRIIB. Our results identify BMP-3 as a novel antagonist of both activin and BMPs and uncover how some of the diverse developmental processes that are regulated by both activin and BNIP signaling can be modulated during embryogenesis. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Gamer, LW (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM laura_gamer@hsdm.harvard.edu FU NIAMS NIH HHS [AR 50174] NR 52 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2005 VL 285 IS 1 BP 156 EP 168 DI 10.1016/j.ydbio.2005.06.012 PG 13 WC Developmental Biology SC Developmental Biology GA 965IP UT WOS:000231944200014 PM 16054124 ER PT J AU Sjostrom, SK Finn, G Hahn, WC Rowitch, DH Kenney, AM AF Sjostrom, SK Finn, G Hahn, WC Rowitch, DH Kenney, AM TI The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors SO DEVELOPMENTAL CELL LA English DT Article ID CELL-CYCLE PROGRESSION; C-MYC; SONIC HEDGEHOG; NEURONAL PRECURSORS; PROTEIN STABILITY; TRANSACTIVATION DOMAIN; KINASE; PROLIFERATION; DEGRADATION; GROWTH AB Myc family transcription factors are destabilized by phosphorylation of a conserved amino-terminal GSK-3 beta motif. In proliferating cerebellar granule neuron precursors (CGNPs), Sonic hedgehog signaling induces N-myc expression, and N-myc protein is stabilized by insulin-like growth factor-mediated suppression of GSK-3 beta. N-myc phosphorylation-mediated degradation is a prerequisite for CGNP growth arrest and differentiation. We investigated whether N-myc phosphorylation and turnover are thus linked to cell cycle exit in primary mouse CGNP cultures and the developing cerebellum. We report that phosphorylation-induced turnover of endogenous N-myc protein in CGNPs increases during mitosis, due to increased priming phosphorylation of N-myc for GSK-3 beta. The priming phosphorylation requires the Cdk1 complex, whose cyclin subunits are indirect Sonic hedgehog targets. These findings provide a mechanism for promoting growth arrest in the final cycle of neural precursor proliferation competency, or for resetting the cell cycle in the G1 phase, by destabilizing N-myc in mitosis. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Kenney, AM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, 1275 York Ave, New York, NY 10021 USA. EM kenneya@mskcc.org FU NCI NIH HHS [K01 CA94223, P01 CA50661]; NINDS NIH HHS [NS047527] NR 64 TC 67 Z9 68 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD SEP PY 2005 VL 9 IS 3 BP 327 EP 338 DI 10.1016/j.devcel.2005.07.014 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 965IR UT WOS:000231944400007 PM 16139224 ER EF